WO2022235714A1 - Systèmes et procédés de régulation du taux de glucose - Google Patents

Systèmes et procédés de régulation du taux de glucose Download PDF

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Publication number
WO2022235714A1
WO2022235714A1 PCT/US2022/027531 US2022027531W WO2022235714A1 WO 2022235714 A1 WO2022235714 A1 WO 2022235714A1 US 2022027531 W US2022027531 W US 2022027531W WO 2022235714 A1 WO2022235714 A1 WO 2022235714A1
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WIPO (PCT)
Prior art keywords
glucose level
subject
glucose
control system
dose
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PCT/US2022/027531
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English (en)
Inventor
Firas H. EL-KHATIB
Edward R. DAMIANO
Himanshu Patel
Michael J. Rosinko
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Beta Bionics, Inc.
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Application filed by Beta Bionics, Inc. filed Critical Beta Bionics, Inc.
Publication of WO2022235714A1 publication Critical patent/WO2022235714A1/fr

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    • A61M5/1723—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure
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Definitions

  • This disclosure relates to glucose control systems, including medical devices that provide glucose control therapy to a subject, glucose level control systems, and ambulatory medicament pumps that deliver medicament to the subject to control glucose level in the subject.
  • Sustained delivery, pump driven medicament injection devices generally include a delivery cannula mounted in a subcutaneous manner through the skin of the subject at an infusion site.
  • the pump draws medicine from a reservoir and delivers it to the subject via the cannula.
  • the injection device typically includes a channel that transmits a medicament from an inlet port to the delivery cannula which results in delivery to the subcutaneous tissue layer where the delivery cannula terminates.
  • Some infusion devices are configured to deliver one medicament to a subject while others are configured to deliver multiple medicaments to a subject.
  • the medicament and/or supplies must be monitored and periodically replaced, which requires the subject keep track of the amount of medicament and/or supplies left. Failure to maintain an adequate supply of medicament and other supplies can disrupt treatment.
  • Disclosed glucose control devices and systems may comprise a medicament pump (AMP) that delivers medicament (e.g., insulin or glucagon) to a subject based at least in part on glucose level (e.g., glucose level) of the subject measured by a glucose sensor.
  • AMP medicament pump
  • the glucose sensor that is operatively connected to the subject, generates glucose level signals that are indicative of the glucose levels of the subject (e.g., a concentration of glucose in subject’s blood or interstitial fluid).
  • the controller of the AMP receives the glucose level signals from the glucose sensor, decodes glucose levels (e.g., measured glucose levels) from the glucose level signals and determines a type, a delivery time and a dose of the medicament that should be delivered to the subject using the glucose levels, one or more control algorithms and values of one or more control parameters.
  • the controller may generate a dose control signal associated with the type, delivery time and dose of medicament and transmit the dose control signal to a medicament delivery system of the AMP, causing the medicament delivery system to deliver the dose of the medicament to the subject at the delivery time.
  • the disclosed glucose control systems may implement methods and algorithms to identify or detect artifacts in the glucose levels associated with the glucose level signals received from the glucose sensor and make adjustments to the delivery of medicament to the subject in order to reduce the risk of hypoglycemia or hyperglycemia in the subject that may be caused by the delivery of medicament based on the glucose level artifacts.
  • the control algorithms may delay, suspend, or expedite the delivery of medicament to the subject, increase or decrease medicament doses delivered to the subject (e.g., with respect to a delivery time and a medicament dose associated with glucose level artifacts).
  • the glucose control system may modify or replace the measured glucose levels identified as artifacts or glucose levels associated with glucose level signals that are received during a time period during which the glucose level artifacts have been identified. Subsequently the glucose control system may use the modified or the replacement glucose levels to generate a dose control signal. In some implementations, in response to identifying glucose level artifacts, the glucose control system may switch to an alternative control process such as an offline mode of operation and generate a dose control signal without using the glucose level signals received from the glucose sensor. In various embodiments, glucose level artifacts identified by the GLCS can be suspected glucose level artifacts.
  • the glucose level artifacts may be glucose levels decoded from glucose level signals that are not associated with a physiological glucose level of the subject.
  • the glucose level artifacts may be transient abnormal changes that are not correlated with variations of the physiological glucose level of the subject.
  • the glucose level artifacts may be associated with non-glucose related variations of the glucose level signal caused by, for example, pressure applied on or near the glucose sensor, variations of certain chemical species in subject’s blood or interstitial fluid, glucose sensor malfunction (e.g., due to the age of the glucose sensor), temperature changes, PH changes of a subject’s blood or interstitial fluid, keeping the glucose sensor on injection site for a long time and the like.
  • the glucose control systems may first identify a glucose level a glucose level variation as an artifact and then determine that the glucose level or the glucose level variation is not associated with a physiological glucose level or physiological glucose level variations of the subject (e.g., by further processing the artifacts).
  • the glucose control system may determine that glucose level data received during a time window includes suspected artifacts and determine that the suspected artifacts are caused by non-glucose related variation of the corresponding glucose level signals by processing the glucose levels decoded from the glucose level signals received during the time window.
  • a glucose level artifact may be referred to herein as an “artifact”.
  • the glucose control systems may identify artifacts based on characteristics of the corresponding glucose level signals (e.g., signal magnitude or temporal behavior of the signal magnitude) received from a glucose sensor operatively connected to the subject. For example, the characteristics of the received glucose level signals may be compared to baseline characteristics determined based on reference data and/or previously received glucose level signals from the subject.
  • characteristics of the corresponding glucose level signals e.g., signal magnitude or temporal behavior of the signal magnitude
  • the glucose control systems may identify artifacts based on characteristics (e.g., magnitude or temporal behavior) of the glucose level data decoded from one or more glucose level signals received from the glucose sensor. For example, the characteristics of the glucose level data associated with the one or more glucose level signals may be compared to baseline characteristics determined based on reference data and/or previously received glucose level data associated with the subject.
  • characteristics e.g., magnitude or temporal behavior
  • the glucose control system may identify artifacts based on spectral content and/or statistical properties of the glucose level data decoded from received glucose level signals. For example, the glucose control systems may compare the spectral content or the statistical properties of glucose data received during a time window with that of other glucose data received during one or more preceding time windows. In some implementations, the glucose control system may also use signals received from other types of sensors (e.g., motion sensor, heart rate sensor, temperature sensor, pressure sensor, blood pressure sensor and the like) to identify artifacts.
  • sensors e.g., motion sensor, heart rate sensor, temperature sensor, pressure sensor, blood pressure sensor and the like
  • the glucose control system may determine the subsequent medicament doses and delivery times based at least in part on the artifact. Additionally, upon detecting an artifact, the control system may modify one or more settings of the glucose control system or modify one or more control parameters used by a control algorithm used for determining medicament dose and medicament delivery time. In some aspects, the modified settings of the glucose control system may restrict selected operations that may increase the risk of hyperglycemia or hypoglycemia in presence of glucose signal artifacts. For example, the glucose control systems may impose an upper bound on the medicament dose or scale the medicament dose. In some aspects, the modified settings may result in decreasing an amount of medicament delivered to the subject. In some aspects, the modified settings may cause the glucose control system to deliver medicament to the subject without using a glucose level signal.
  • the glucose control system may generate a substitute dose control signal based at least in part on the artifacts or the portion of the glucose level data that includes the artifacts.
  • the substitute dose control signal may be a dose control signal generated by the glucose control system using a control algorithm operated in an artifact compensation mode.
  • the control algorithm may generate the dose control signal using an artifact compensation process.
  • the substitute dose control signal may be delivered to the medicament delivery system and result in delivery of substitute glucose control therapy associated with the corresponding artifact compensation process.
  • the substitute glucose control therapy may be a delayed, expedited glucose therapy or a glucose therapy with reduced or increased medicament dose.
  • the artifact compensation process may modify or replace one or more glucose levels in the glucose level data and generate the dose control signal using the modified glucose levels. In some aspects, the artifact compensation process may generate the substitute dose control signal without using the glucose level data.
  • Certain embodiments of the present disclosure relate to an ambulatory medicament pump configured to deliver glucose control therapy to a subject and to adjust the glucose control therapy in response to identifying a glucose level artifact in glucose level data received from a glucose sensor connected to the subject.
  • the ambulatory medicament pump may include: a pump controller configured to cause the ambulatory medicament pump to deliver glucose control therapy to a subject up on receiving a dose control signal, a glucose sensor interface configured to receive a glucose level signal from the glucose sensor, where the glucose level signal comprises encoded glucose level data, a non -transitory memory configured to store specific computer-executable instructions and a control algorithm configured to generate the dose control signal to provide the glucose control therapy to the subject via the ambulatory medicament pump, where the glucose control therapy comprises administration of doses of medicament in response to glucose level excursions indicated by the glucose level data, and an electronic processor in communication with the non -transitory memory and configured to execute the specific computer-executable instructions to at least: receive, via the glucose sensor interface, the glucose level signal; decode the glucose level
  • the control algorithm In the artifact compensation mode, the control algorithm generates the dose control signal using one or more of a plurality of artifact compensation processes comprising: delaying doses of medicament in response to glucose level excursions, reducing doses of medicament in response to glucose level excursions, expediting doses of medicament in response to glucose level excursions, increasing doses of medicament in response to glucose level excursions, operating the control algorithm in an offline mode of operation.
  • the offline mode of operation corresponds to operation of the control algorithm when the glucose level data associated with the glucose level signal is not used in generating the dose control signal or generating the dose control signal using a modified glucose level different from a glucose level indicated by the glucose level data.
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to adjust glucose control therapy delivered to a subject by an ambulatory medicament pump in response to identifying a glucose level artifact in glucose level data received from a glucose sensor connected to the subject.
  • the glucose level control system may include: a pump controller configured to cause the ambulatory medicament pump to deliver glucose control therapy to a subject upon receiving a dose control signal, a glucose sensor interface configured to receive a glucose level signal from the glucose sensor, where the glucose level signal comprises encoded glucose level data, a non -transitory memory configured to store specific computer-executable instructions and a control algorithm configured to generate the dose control signal to provide the glucose control therapy to the subject via the ambulatory medicament pump.
  • the glucose control therapy comprises administration of doses of medicament in response to glucose level excursions indicated by the glucose level data.
  • the glucose level control system further includes an electronic processor in communication with the non-transitory memory and configured to execute the specific computer-executable instructions to at least: receive, via the glucose sensor interface, the glucose level signal, decode the glucose level data from the glucose level signal, determine that the glucose level data has the glucose level artifact and in response to determining that the glucose level data has the glucose level artifact, operate the control algorithm in an artifact compensation mode to reduce a risk of hypoglycemia or hyperglycemia in the subject. In the artifact compensation mode, the control algorithm generates the dose control signal using one or more of a plurality of artifact compensation processes.
  • Certain embodiments of the present disclosure relate to a computer implemented method of adjusting glucose control therapy delivered to a subject by a glucose level control system in response to identifying a glucose level artifact in glucose level data received from a glucose sensor connected to the subject, where the glucose level control system is configured to deliver glucose control therapy to the subject upon receiving a dose control signal generated by a control algorithm.
  • the computer-implemented method may be performed by an electronic processor of the glucose level control system, where the electronic processor is configured to execute specific computer-executable instructions stored in a non- transitory memory connected to the electronic processor.
  • the method may include receiving, via a glucose sensor interface, a glucose level signal; decoding the glucose level data from the glucose level signal; determining that the glucose level data has the glucose level artifact; and, in response to determining that the glucose level data has the glucose level artifact, operating the control algorithm in an artifact compensation mode to reduce a risk of hypoglycemia or hyperglycemia in the subject, where in the artifact compensation mode, the control algorithm generates the dose control signal using one or more of a plurality of artifact compensation processes.
  • the artifact compensation processes can include delaying doses of medicament in response to glucose level excursions, reducing doses of medicament in response to glucose level excursions, expediting doses of medicament in response to glucose level excursions, increasing doses of medicament in response to glucose level excursions, operating the control algorithm in an offline mode of operation, and/or generating the dose control signal using a modified glucose level different from a glucose level indicated by the glucose level data.
  • the offline mode of operation can correspond to operation of the control algorithm when the glucose level data associated with the glucose level signal is not used in generating the dose control signal.
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify an autonomously generated insulin dose generated by a control algorithm that generates a dose control signal that causes glucose control therapy to be provided to a subject.
  • the autonomously generated insulin dose may be modified responsive to user input received in response to interaction with a user interface by a user.
  • the glucose level control system may include: a medicament delivery interface configured to operatively connect to a medicament pump for infusing medicament into the subject; a memory configured to store specific computer-executable instructions; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: generate a calculated insulin dose based at least in part on therapy provided to the subject over a first time period; where the control algorithm is configured to generate first dose control signals to administer first insulin doses to the subject based on the calculated insulin dose; receive an indication of a modification to the calculated insulin dose to obtain a modified insulin dose in response to the user input received in response to the interaction with the user interface by the user; and/or use the control algorithm to generate second dose control signals to administer second insulin doses to the subject over a second time period based on the modified insulin dose.
  • the system of the preceding paragraph can include any combination and/or sub-combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least output an indication of the calculated insulin dose on a display; where the calculated insulin dose comprises a calculated basal rate and the modified insulin dose comprises a modified basal rate; where the calculated basal rate is one of a plurality of calculated basal rates; where at least one calculated basal rate corresponds to a different segment of a day than at least one other calculated basal rate of the plurality of calculated basal rates; where the modification to the calculated insulin dose comprises a modification to each calculated basal rate of the plurality of calculated basal rates; where the modification to the calculated insulin dose comprises a modification to at least one calculated basal rate of the plurality of calculated basal rates; where the modification to the calculated insulin dose omits a modification to at least one calculated basal rate of the plurality of calculated basal rates; where the indication of the modification to the calculated insulin dose comprises a scaling factor
  • Certain embodiments of the present disclosure relate to a computer- implemented method of modifying an autonomously generated insulin dose generated by a control algorithm that generates a dose control signal that causes glucose control therapy to be provided to a subject.
  • the autonomously generated insulin dose may be modified responsive to user input received in response to interaction with a user interface by a user.
  • the computer-implemented method may be implemented by a hardware processor of a glucose level control system configured to generate the dose control signal.
  • the computer-implemented method may include: generating a calculated insulin dose based at least in part on therapy provided to the subject over a first time period; where the control algorithm is configured to generate first dose control signals to administer first insulin doses to the subject based on the calculated insulin dose; receiving an indication of a modification to the calculated insulin dose to obtain a modified insulin dose in response to the user input received in response to the interaction with the user interface by the user; and/or using the control algorithm to generate second dose control signals to administer second insulin doses to the subject over a second time period based on the modified insulin dose.
  • the computer-implemented method of the preceding paragraph can include any combination and/or sub-combination of any one or more of the following features: where the method further comprises outputting an indication of the calculated insulin dose on a display; where the calculated insulin dose comprises a calculated basal rate and the modified insulin dose comprises a modified basal rate; where the calculated basal rate is one of a plurality of calculated basal rates; where at least one calculated basal rate corresponds to a different segment of a day than at least one other calculated basal rate of the plurality of calculated basal rates; where the modification to the calculated insulin dose comprises a modification to each calculated basal rate of the plurality of calculated basal rates; where the modification to the calculated insulin dose comprises a modification to at least one calculated basal rate of the plurality of calculated basal rates; where the modification to the calculated insulin dose omits a modification to at least one calculated basal rate of the plurality of calculated basal rates; where the indication of the modification to the calculated insulin dose comprises a scaling factor to apply to the calculated insulin dose; where
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify an autonomously generated basal rate generated by a control algorithm that generates a dose control signal that causes glucose control therapy to be provided to a subject.
  • the autonomously generated basal rate may be modified responsive to user input received in response to interaction with a user interface by a user.
  • the glucose level control system may include: a medicament delivery interface configured to operatively connect to a medicament pump for infusing medicament into the subject; a memory configured to store specific computer-executable instructions; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: generate an indication of a basal rate via a control algorithm configured to control a glucose level in the subject; where the basal rate is determined by the control algorithm based at least in part on preceding periods of glycemic control in the subject; generate a display of a manual basal screen comprising a manual basal control element and a basal recommendation comprising the indication of the basal rate determined by the control algorithm; receive, via user interaction with the manual basal control element, an indication of a modification to the basal rate; modify the basal rate based on the indication of the modification to the basal rate to obtain a modified basal rate; and/or operate the control algorithm for automatic generation of the dose control signal configured to operate the medicament pump to control the glucose level in the subject based
  • the system of the preceding paragraph can include any combination and/or sub-combination of any one or more of the following features: where the system further includes a wireless electronic communications interface configured to receive the indication of the modification to the basal rate from an electronic device remote from the medicament pump; where the hardware processor is further configured to generate the display of the manual basal screen by causing the electronic device remote from the medicament pump to display the manual basal screen; where the indication of the basal rate comprises an indication of a plurality of basal rates, each basal rate of the plurality of basal rates corresponding to a different segment of a day than the other basal rates of the plurality of basal rates; where the modification to the basal rate comprises a modification to at least one basal rate of the plurality of basal rates; where the modification to the basal rate omits a modification to at least one basal rate of the plurality of basal rates; where the indication of the modification to the basal rate comprises a scaling factor to apply to the basal rate to obtain the modified basal rate; where the indication
  • Certain embodiments of the present disclosure relate to a computer- implemented method of modifying an autonomously generated basal rate generated by a control algorithm that generates a dose control signal that causes glucose control therapy to be provided to a subject.
  • the autonomously generated basal rate may be modified responsive to user input received in response to interaction with a user interface by a user.
  • the computer- implemented method may be implemented by a hardware processor configured to generate the dose control signal.
  • the computer-implemented method may include: generating an indication of a basal rate via a control algorithm configured to control a glucose level in the subject; where the basal rate is determined by the control algorithm based at least in part on preceding periods of glycemic control in the subject; generating a display of a manual basal screen comprising a manual basal control element and a basal recommendation comprising the indication of the basal rate determined by the control algorithm; receiving, via user interaction with the manual basal control element, an indication of a modification to the basal rate; modifying the basal rate based on the indication of the modification to the basal rate to obtain a modified basal rate; and/or operating the control algorithm for automatic generation of the dose control signal configured to operate a medicament pump to control the glucose level in the subject based at least in part on the modified basal rate.
  • the computer-implemented method of the preceding paragraph can include any combination and/or sub-combination of any one or more of the following features: where said generating the display of the manual basal screen comprises causing an electronic device remote from the medicament pump to display the manual basal screen; where the indication of the basal rate comprises an indication of a plurality of basal rates, each basal rate of the plurality of basal rates corresponding to a different segment of a day than the other basal rates of the plurality of basal rates; where the modification to the basal rate comprises a modification to at least one basal rate of the plurality of basal rates; where the modification to the basal rate omits a modification to at least one basal rate of the plurality of basal rates; where the indication of the modification to the basal rate comprises a scaling factor to apply to the basal rate to obtain the modified basal rate; where the indication of the modification to the basal rate comprises an indication of a new nominal basal rate; where the indication of the modification to the basal rate comprises an indication
  • Certain embodiments of the present disclosure relate to a glucose control system configured to modify an operating mode of a control algorithm that generates a dose control signal that causes glucose control therapy to be provided to a subject; and/or where the operating mode is associated with an adaptation range of a control parameter of the control algorithm.
  • the glucose control system may include: a medicament delivery interface configured to operatively connect to a medicament pump for infusing medicament into the subject; a memory configured to store specific computer-executable instructions and therapy data; and/or a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions.
  • the computer-executable instructions may be configured to at least: receive a glucose level signal from a glucose level sensor operatively connected to the subject; cause first therapy to be delivered to the subject during a first therapy period; where the first therapy is delivered based at least in part on a first value of the control parameter of the control algorithm used to generate the dose control signal;where the first value is selected from a first adaptation range associated with a first operating mode of the control algorithm; receive an indication to operate the control algorithm in a second operating mode; where the indication is received in response to a user interacting with a user interface; switch the control algorithm from the first operating mode to the second operating mode responsive to receiving the indication to operate in the second operating mode; where the second operating mode is associated with a second adaptation range that results in a higher medicament response than the first adaptation range within a glucose response period after the glucose level signal indicates a glucose excursion in the subject; and cause second therapy to be delivered to the subject during a second therapy period occurring after the control algorithm is switched to the second operating mode; where the second therapy is delivered based at least
  • the system of the preceding paragraph can include any combination and/or sub-combination of any one or more of the following features: where the second operating mode is associated with more aggressive treatment of the subject than the first operating mode; where the second operating mode is associated with more glucose control therapy of the subject than the first operating mode; where the second adaptation range comprises a subset of the first adaptation range; where the second adaptation range at least partially overlaps the first adaptation range; where a step size between values of the second adaptation range is larger than a step size between values of the first adaptation range; where a range between a minimum and maximum value of the second adaptation range and a range between a minimum and maximum value of the first adaptation range is the same; where the hardware processor is further configured to execute the specific computer-executable instructions to at least: automatically switch the control algorithm from the second operating mode to the first operating mode responsive to a trigger; and cause third therapy to be delivered to the subject during a third therapy period occurring after the control algorithm is automatically switched to the first operating mode; where automatically switching the control algorithm to the first operating mode from the second operating
  • Certain embodiments of the present disclosure relate to a computer- implemented method of modifying an operating mode of a control algorithm that generates a dose control signal that causes therapy to be provided to a subject using a glucose level control system; where the operating mode is associated with an adaptation range of a control parameter of the control algorithm.
  • the computer-implemented method may be performed by a hardware processor configured to generate the dose control signal for the glucose level control system.
  • the computer-implemented method may include: receiving a glucose level signal from a glucose level sensor operatively connected to the subject; causing first therapy to be delivered to the subject during a first therapy period; where the first therapy is delivered based at least in part on a first value of the control parameter of the control algorithm used to generate the dose control signal; where the first value is selected from a first adaptation range associated with a first operating mode of the control algorithm; receiving an indication to operate the control algorithm in a second operating mode; where the indication is received in response to a user interacting with a user interface; switching the control algorithm from the first operating mode to the second operating mode responsive to receiving the indication to operate in the second operating mode; where the second operating mode is associated with a second adaptation range that results in a higher medicament response than the first adaptation range within a glucose response period after the glucose level signal indicates a blood glucose excursion in the subject; and causing second therapy to be delivered to the subject during a second therapy period occurring after the control algorithm is switched to the second operating mode; where the second therapy is delivered based at least
  • the method of the preceding paragraph can include any combination and/or sub-combination of any one or more of the features identified with respect to the aforementioned system. Further, the method of the preceding paragraph can include any combination and/or sub-combination of any one or more of the following features: where a breadth of the second adaptation range is less than a breadth of the first adaptation range; where the first adaptation range and the second adaptation range comprise discrete values of the control parameter of the control algorithm; where a step size between values of the second adaptation range is larger than a step size between values of the first adaptation range; where the method further includes automatically switching the control algorithm from the second operating mode to the first operating mode responsive to a trigger; and causing third therapy to be delivered to the subject during a third therapy period occurring after the control algorithm is automatically switched to the first operating mode; where the trigger is based on a statistical comparison of first glycemic control of blood glucose in the subject when using the first adaptation range and second glycemic control of blood glucose in the subject when using the second adaptation range; where
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event indicated by a low glucose level or after the subject receives carbohydrate treatment.
  • the glucose level control system may include: a medicament delivery interface configured to operatively connect to the ambulatory medicament pump for delivering medicament to the subject; where the medicament includes insulin or an insulin analog; a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; a memory configured to store specific computer-executable instructions and a control algorithm configured to generate a dose control signal for causing delivery of medicament by the ambulatory medicament pump; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: receive a glucose level signal from a glucose sensor operatively connected to the subject; based on the glucose level signal, determine a glucose level of the subject; determine that the glucose level is equal to or greater than a first threshold glucose level; in response to determining that the glucose level is equal to or greater than the first threshold glucose level, operate the glucose level control system in a first mode in which the control algorithm generates the dose control signal based on the glucose level signal to cause the ambulatory medicament pump to administer glucose control therapy including basal doses
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one hypoglyce
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event indicated by a low glucose level or after the subject receives carbohydrate treatment.
  • the glucose level control system may include: a medicament delivery interface configured to operatively connect to the ambulatory medicament pump for delivering medicament to the subject; where the medicament includes insulin or an insulin analog; a memory configured to store specific computer-executable instructions and a control algorithm configured to generate a dose control signal for causing delivery of medicament by the ambulatory medicament pump; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: based on a glucose level signal associated with the subject, determine a glucose level of the subject; determine that the glucose level is equal to or greater than a first threshold glucose level; in response to determining that the glucose level is equal to or greater than the first threshold glucose level, operate the glucose level control system in a first mode in which the control algorithm generates the dose control signal based on the glucose level signal to cause the ambulatory medicament pump to administer glucose control therapy including basal doses and correction doses of medicament to the subject; determine that at least one hypoglycemic event criterion selected from a plurality of hypoglyce
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the system further includes a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; where the plurality of hypoglycemic event criteria includes determining that user input signals received via the user interface controller correspond to a user indication of carbohydrate treatment; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level signal from a glucose sensor operatively connected to the subject; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level of the subject from a user input; where the plurality of hypoglycemic event criteria includes determining that the glucose level signal indicates carbohydrate treatment by the subject and determining that a physiological sensor other than the glucose sensor indicates carbohydrate treatment by the subject; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine that the glucose level is equal to or greater than a recovery threshold glucose level while the glucose
  • the system of the preceding two paragraphs can include any combination and/or sub combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one hypog
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event indicated by a low glucose level or after the subject receives carbohydrate treatment
  • the glucose level control system including: a medicament delivery interface configured to operatively connect to the ambulatory medicament pump for delivering medicament to the subject; where the medicament includes insulin or an insulin analog; a memory configured to store specific computer-executable instructions and a control algorithm configured to generate a dose control signal for causing delivery of medicament by the ambulatory medicament pump; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: receive a glucose level signal from a glucose sensor operatively connected to the subject; based on the glucose level signal, determine a glucose level of the subject; determine that the glucose level is equal to or greater than a first threshold glucose level; in response to determining that the glucose level is equal to or greater than the first threshold glucose level, operate the glucose
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the system further includes a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; where the plurality of hypoglycemic event criteria includes determining that user input signals received via the user interface controller correspond to a user indication of carbohydrate treatment; where the plurality of hypoglycemic event criteria includes determining that a physiological sensor other than the glucose sensor indicates carbohydrate treatment by the subject; where the hardware processor is further configured to execute the specific computer-executable instructions to at least in response to determining that the at least one hypoglycemic event criterion is met, operate the glucose level control system in the recovery mode in which the control algorithm does not cause administration of the at least one of basal doses or correction doses of medicament to the subject for a recovery duration; where the recovery duration is a minimum recovery duration; where the recovery duration is a maximum recovery duration; where the maximum recovery duration includes at least one of 3 hours, 2 hours, 1.5 hours
  • the system of the preceding two paragraphs can include any combination and/or sub combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one hypog
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event indicated by a low glucose level or after the subject receives carbohydrate treatment
  • the glucose level control system including: a medicament delivery interface configured to operatively connect to the ambulatory medicament pump configured to deliver medicament to the subject; a memory configured to store specific computer-executable instructions and a control algorithm configured to generate a dose control signal for causing delivery of medicament by the ambulatory medicament pump; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: based on a glucose level signal associated with the subject, determine a glucose level of the subject; determine that the glucose level is equal to or greater than a first threshold glucose level; operate the glucose level control system in a first mode in which the control algorithm generates the dose control signal based on the glucose level signal to cause the ambulatory medicament pump to administer glucose control therapy including basal doses and
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the medicament includes insulin or an insulin analog; where the system further includes a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; where the at least one of hypoglycemic event criterion includes determining that user input signals received via the user interface controller correspond to a user indication of carbohydrate treatment; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level signal from a glucose sensor operatively connected to the subject; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level of the subject from a user input; where the at least one of hypoglycemic event criterion includes determining that the glucose level is equal to or less than a low glucose level corresponding to the hypoglycemic event, determining that the glucose level signal indicates carbohydrate treatment by the subject, and determining that a physiological sensor other than the glucose sensor indicates carb
  • the system of the preceding two paragraphs can include any combination and/or sub - combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event indicated by a low glucose level or after the subject receives carbohydrate treatment
  • the glucose level control system including: a medicament delivery interface configured to operatively connect to the ambulatory medicament pump configured to deliver medicament to the subject; a memory configured to store specific computer-executable instructions and a control algorithm configured to generate a dose control signal for causing delivery of medicament by the ambulatory medicament pump; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: based on a glucose level signal associated with the subject, determine a glucose level of the subject; determine that the glucose level is equal to or greater than a first threshold glucose level; operate the glucose level control system in a first mode in which the control algorithm generates the dose control signal based on the glucose level signal to cause the ambulatory medicament pump to administer glucose control therapy including basal doses and
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the medicament includes insulin or an insulin analog; where the system further includes a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; where the at least one of hypoglycemic event criterion includes determining that user input signals received via the user interface controller correspond to a user indication of carbohydrate treatment; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level signal from a glucose sensor operatively connected to the subject; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level of the subject from a user input; where the at least one of hypoglycemic event criterion includes determining that the glucose level is equal to or less than a low glucose level corresponding to the hypoglycemic event, determining that the glucose level signal indicates carbohydrate treatment by the subject, and determining that a physiological sensor other than the glucose sensor indicates carb
  • the system of the preceding two paragraphs can include any combination and/or sub - combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event indicated by a low glucose level or after the subject receives carbohydrate treatment
  • the glucose level control system including: a medicament delivery interface configured to operatively connect to the ambulatory medicament pump configured to deliver medicament to the subject; a memory configured to store specific computer-executable instructions and a control algorithm configured to generate a dose control signal for causing delivery of medicament by the ambulatory medicament pump; and a hardware processor in communication with the memory and configured to execute the specific computer-executable instructions to at least: based on a glucose level signal associated with the subject, determine a glucose level of the subject; determine that the glucose level is equal to or greater than a first threshold glucose level; operate the glucose level control system in a first mode in which the control algorithm generates the dose control signal based on the glucose level signal to cause the ambulatory medicament pump to administer glucose control therapy including basal doses and
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the medicament includes insulin or an insulin analog; where the system further includes a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; where the at least one of hypoglycemic event criterion includes determining that user input signals received via the user interface controller correspond to a user indication of carbohydrate treatment; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level signal from a glucose sensor operatively connected to the subject; where the hardware processor is further configured to execute the specific computer-executable instructions to at least receive the glucose level of the subject from a user input; where the at least one of hypoglycemic event criterion includes determining that the glucose level is equal to or less than a low glucose level corresponding to the hypoglycemic event, determining that the glucose level signal indicates carbohydrate treatment by the subject, and determining that a physiological sensor other than the glucose sensor indicates carb
  • the system of the preceding two paragraphs can include any combination and/or sub combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one hypog
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to update a dose control signal to cause an ambulatory medicament pump to suspend delivery of at least one of basal doses or correction doses of medicament to a subject, to determine that at least one reactivation criterion of a plurality of reactivation criteria is satisfied, and to update the dose control signal to cause the ambulatory medicament pump to resume delivery of the at least one of basal doses or correction doses of medicament to the subject
  • the glucose level control system including: a medicament delivery interface configured to operatively connect to an ambulatory medicament pump for delivering medicament to the subject; where the medicament includes insulin or an insulin analog; a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; a data interface configured to connect to a glucose sensor operatively connected to the subject; a non-transitory memory configured to store specific computer- executable instructions and a control algorithm configured to generate a dose control signal for causing delivery of medicament by the ambulatory medicament pump; and
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the critical low threshold level is about 65 mg/dl; where the reactivation threshold level is between about 110 mg/dl and about 140 mg/dl; where causing the ambulatory medicament pump to resume delivery of the at least one of basal doses or correction doses of medicament to the subject includes causing the ambulatory medicament pump to gradually increase, over a second period of time, the at least one of basal doses or correction doses of medicament includes basal doses of medicament to the subject; where the second period of time includes between about 5 minutes and about 120 minutes; and/or where causing the ambulatory medicament pump to resume delivery of the at least one of basal doses or correction doses of medicament to the subject includes causing the ambulatory medicament pump to deliver, after passage of the second period of time, basal doses at a constant rate.
  • the system of the preceding two paragraphs can include any combination and/or sub - combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one
  • Certain embodiments of the present disclosure relate to a glucose level control system configured to generate a dose control signal configured to cause an ambulatory medicament pump to administer modified basal doses of medicament to a subject and to generate the dose control signal configured to cause the ambulatory medicament pump to administer ramp-up basal doses of medicament to the subject
  • the glucose level control system including: a data interface configured to connect to a glucose sensor operatively connected to the subject; a non-transitory memory configured to store specific computer-executable instructions and a control algorithm configured to generate the dose control signal for causing delivery of medicament by an ambulatory medicament pump; and a hardware processor in communication with the non-transitory memory and configured to execute the specific computer-executable instructions to at least: determine a glucose level of the subject; initiate a first intervention including generating the dose control signal configured to cause the ambulatory medicament pump to administer glucose control therapy including basal doses and correction doses of medicament to the subject; determine that one or more of a plurality of critical low criteria are satisfied; in response to determining that
  • the system of the preceding paragraph can include any combination and/or sub combination of any one or more of the following features: where the system further includes: a medicament delivery interface configured to operatively connect to the ambulatory medicament pump for delivering medicament to the subject; where the medicament includes insulin or an insulin analog; a user interface controller configured to receive user input signals corresponding to user interaction with a user interface; where the hardware processor is further configured to execute the specific computer-executable instructions to at least: receive, via the data interface from the glucose sensor, a glucose level signal associated with the subject; where determining the glucose level of the subject includes estimating the glucose level of the subject; where a critical low threshold level is about 65 mg/dl; where the plurality of critical low criteria includes a determination that the glucose level of the subject is less than or equal to a critical low threshold level; where the determination that the glucose level of the subject is less than or equal to the critical low threshold level includes at least one of: receiving a measured glucose level of the subject that is less than or equal to the critical low threshold level; or estimating that
  • the system of the preceding two paragraphs can include any combination and/or sub - combination of any one or more of the following features: where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine a value for the recovery threshold glucose level based on the glucose level of the subject when it is determined that the at least one hypoglycemic event criterion is met; where the value is at least one of 170 mg/dl when the glucose level of the subject is 40 mg/dl, 150 mg/dl when the glucose level of the subject is 45 mg/dl, 135 mg/dl when the glucose level of the subject is 50 mg/dl, 130 mg/dl when the glucose level of the subject is 55 mg/dl, or 120 mg/dl when the glucose level of the subject is 65 mg/dl; where the hardware processor is further configured to execute the specific computer-executable instructions to at least determine the value for the recovery threshold glucose level to be relatively higher the lower the glucose level of the subject is determined to be when it is determined that the at least one
  • any of the aforementioned embodiments may be combined.
  • a single automated blood glucose control system may be configured to implement one or more of the aforementioned embodiments.
  • FIG. 1A illustrates an example glucose level control system that provides glucose level control via an ambulatory medicament pump.
  • FIG. IB illustrates another example glucose level control system that provides glucose level control via an ambulatory medicament pump.
  • FIG. 1C illustrates a further example glucose level control system that provides glucose level control via an ambulatory medicament pump.
  • FIG. 2A shows a block diagram of an example glucose level control system.
  • FIG. 2B shows a block diagram of another example glucose level control system.
  • FIG. 2C shows a block diagram of another example glucose level control system.
  • FIG. 2D shows a block diagram of another example glucose level control system.
  • FIG. 3 is a schematic of an example glucose level control system that includes an electronic communications interface.
  • FIG. 4A shows a block diagram of an example glucose level control system in online operation mode.
  • FIG. 4B shows a block diagram of an example glucose level control system in offline operation mode.
  • FIG. 5 illustrates a block diagram of a glucose level control system in accordance with certain embodiments.
  • FIG. 6 illustrates a block diagram of a controller system in accordance with certain embodiments.
  • FIG. 7 presents a flowchart of an example carbohydrate therapy equivalence tracking process in accordance with certain embodiments.
  • FIG. 8 presents a flowchart of an example backup therapy protocol generation process in accordance with certain embodiments.
  • FIG. 9 presents a flowchart of an example control parameter modification tracking process in accordance with certain embodiments.
  • FIG. 10 illustrates an example backup therapy protocol in accordance with certain embodiments.
  • FIG. 11 illustrates an example control parameter modification report in accordance with certain embodiments.
  • FIG. 12 illustrates an example meal selection report that may be included as part of some implementations of the control parameter modification report of FIG. 11 in accordance with certain embodiments.
  • FIG. 13 presents a flowchart of an example automated glucose level control refinement process in accordance with certain embodiments.
  • FIG. 14A illustrates a simulation of glucose level control of a subject with Tmax set to 65 minutes.
  • FIG. 14B illustrates a simulation of glucose level control of a subject with Tmax set to 15 minutes.
  • FIG. 14C illustrates a simulation of glucose level control of a subject with Tmax set to 130 minutes.
  • FIG. 15 illustrates an example of glucose level signal (CGM trace) and some of the parameters associated with glycemic control using a glucose level control system.
  • FIG. 16 presents a flowchart of an example automated glucose level control refinement process based on an adjustment function in accordance with certain embodiments.
  • FIG. 17 illustrates some examples of statistical quantities that may be generated and utilized by the glucose level control system as part of statistical analysis.
  • FIG. 18 presents a flowchart of an example automated glucose level control refinement process in accordance with certain embodiments.
  • FIG. 19 presents a flowchart of an example dose mode transition process in accordance with certain embodiments.
  • FIG. 20 presents a flowchart of an example automated dose mode transition process in accordance with certain embodiments.
  • FIG. 21 presents a flowchart of a second example automated dose mode transition process in accordance with certain embodiments.
  • FIG. 22 shows an example glucose-time plot showing oscillations in a glucose level of a hypothetical subject.
  • FIG. 23 shows an example glucose level control system configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event indicated by a low glucose level or after the subject receives carbohydrate treatment.
  • FIG. 24 shows another example glucose-time plot showing a recovery threshold duration that initiates after a glucose level drops below a low glucose level.
  • FIG. 25 shows another example glucose-time plot showing a hypothetical scenario where the recovery threshold duration is not satisfied until after a glucose level has reached a reactivation threshold level.
  • FIG. 26 shows another example glucose-time plot showing a hypothetical scenario where the recovery threshold duration is not satisfied until after a glucose level has reached a reactivation threshold level.
  • FIG. 27 shows another example glucose-time plot showing a hypothetical scenario where the recovery threshold duration is not satisfied until after a glucose level has reached a reactivation threshold level.
  • FIG. 28 shows a flow diagram illustrating an example method that may be used by a glucose level control system to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event.
  • FIG. 29 shows another flow diagram illustrating an example method that may be used by a glucose level control system to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after the subject experiences a hypoglycemic event.
  • FIG. 30 shows a logical flow diagram illustrating an example method that may be used by a glucose level control system to enter a recovery mode and/or a reactivation mode after the subject experiences a hypoglycemic event.
  • FIG. 31A illustrates a perspective view of an example ambulatory medical device.
  • FIG. 3 IB illustrates a cross sectional view of the ambulatory medical device shown in FIG. 5 A.
  • FIG. 32 illustrates different systems included in an example ambulatory medical pump (AMP).
  • AMP example ambulatory medical pump
  • FIG. 33A shows an example of glucose level data that includes artifacts.
  • FIG. 33B shows an example of temporal variation of a glucose level artifact associated with a velocity of a subject’s glucose level.
  • FIG. 33C shows an example of temporal variation of a glucose level artifact associated with an acceleration of a subject’s glucose level.
  • FIG. 34 shows an example of glucose level data that includes glucose level artifacts and an example of modified glucose data determined by the glucose level control system to replace the portion of the glucose level data that includes the glucose level artifacts.
  • FIG. 35 is a flow diagram showing an example of a computer-implemented method that may be used by the glucose level control system to manage glucose control therapy delivered to a subject in the presence of a glucose level artifact in the glucose levels associated with the glucose level signals received from a glucose sensor.
  • FIG. 36 is a flow diagram showing another example of a computer-implemented method that may be used by the glucose level control system to manage glucose control therapy delivered to a subject in the presence of a glucose level artifact in the glucose levels associated with the glucose level signals received from a glucose sensor.
  • FIG. 37 is a flow diagram showing another example of a computer-implemented method that may be used by the glucose level control system to manage glucose control therapy delivered to a subject in the presence of artifacts in the glucose level data decoded from glucose level signals received from a glucose sensor.
  • FIG. 38 is a flow diagram showing another example of a computer-implemented method that may be used by the glucose level control system to manage glucose control therapy delivered to a subject in the presence of artifacts in the glucose level data decoded from glucose level signals received from a glucose sensor.
  • FIG. 39 is a flow diagram showing another example of a computer-implemented method that may be used by the glucose level control system to manage glucose control therapy delivered to a subject in the presence of a glucose level artifact in the glucose level data decoded from glucose level signals received from a glucose sensor.
  • FIG. 40 is a diagram showing a glucose level control system with a dose control signal generation system configured to compensate for glucose level artifacts.
  • FIG. 41 illustrates a flowchart of an example process directed to manual modification of an autonomously generated medicament dose in accordance with certain embodiments.
  • FIG. 42 illustrates a flowchart of an example of a manual basal rate modification process in accordance with certain embodiments.
  • FIG. 43 is a schematic illustrating a computer system that can be implemented in various embodiments of the described subject matter.
  • Some embodiments described herein pertain to medicament infusion systems for one or more medicaments and the components of such systems (e.g., infusion pumps, medicament cartridges, cartridge connectors, lumen assemblies, infusion connectors, infusion sets, etc.). Some embodiments pertain to methods of manufacturing infusion systems and components thereof. Some embodiments pertain to methods of using any of the foregoing systems or components for infusing one or more medicaments (e.g., pharmaceutical, hormone, etc.) to a subject.
  • an infusion system may include an infusion pump, which can include one or more medicament cartridges or can have an integrated reservoir of medicament.
  • An infusion system may include medicament cartridges and cartridge connectors, but not a pump.
  • An infusion system may include cartridge connectors and an infusion pump, but not medicament cartridges.
  • An infusion system may include infusion connectors, a lumen assembly, cartridge connectors, an infusion pump, but not medicament cartridges or an infusion set.
  • a glucose level control system can operate in conjunction with an infusion system to infuse one or more medicaments, including at least one glucose level control agent, into a subject.
  • An infusion system may include a glucose sensor interface that can receive glucose level signals from a glucose sensor operatively connected to a subject. The glucose level signals may be received via a wireless link established between the glucose sensor and the infusion system.
  • the infusion system may have a controller that controls the infusion of the medicament from the medicament cartridge to the subject based at least in part on the received glucose level signals.
  • the controller of the infusion system may analyze the glucose level data associated with the received glucose level signals to identify glucose level artifacts based on the temporal behavior or the magnitude of the glucose level and determine the medicament dose and delivery time based at least in part on the identified glucose level artifacts.
  • Any feature, structure, component, material, step, or method that is described and/or illustrated in any embodiment in this specification can be used with or instead of any feature, structure, component, material, step, or method that is described and/or illustrated in any other embodiment in this specification. Additionally, any feature, structure, component, material, step, or method that is described and/or illustrated in one embodiment may be absent from another embodiment.
  • certain embodiments disclosed herein relate to a glucose level control system that is capable of supporting different operating modes associated with different adaptation ranges used to generate dose control signals for delivering medicament to a subject.
  • the different adaptation ranges may be associated with a value or a change in value of one or more control parameters used by a control algorithm that controls the administering of medicament to a subject.
  • control parameter may be associated with the quantity of medicament, a delivery rate of medicament, a step -size or graduation used to modify the quantity of medicament between administrations of the medicament, a timing of supplying medicament to the subject, a glucose absorption rate, a time until the concentration of insulin in blood plasma for a subject reaches half of the maximum concentration, a time until the concentration of insulin in blood plasma for a subject reaches a maximum concentration, or any other control parameter that can impact a timing or quantity of medicament (e.g., insulin or counter-regulatory agent) supplied or administered to a subject.
  • a timing or quantity of medicament e.g., insulin or counter-regulatory agent
  • supporting different operating modes enables a user (e.g., a healthcare provider, parent, guardian, the subject receiving treatment, etc.) to modify the operating mode of an ambulatory medicament device.
  • the operating mode may be modified automatically.
  • modifying the operating mode enables different dosing modes to be supported.
  • supporting different dosing modes enables an ambulatory medicament device to be used by different types of subjects, and/or a subject under different conditions (e.g., when exercising, before, during, or after puberty, under different health conditions, etc.).
  • Other patients use medicament pumps to help manage their diabetes.
  • These medicament pumps may be controlled manually or may be closed using an autonomous system.
  • a glucose level control system may operate in a closed loop mode that enables the glucose level control system to automatically determine insulin dosing using a control algorithm and one or more sensor signals received at a sensor interface from one or more sensors.
  • These sensors may include continuous glucose monitoring (CGM) sensors operatively coupled to a subject.
  • the CGM sensors may provide measurements of glucose levels of the subject to the glucose level control system, which may autonomously determine the insulin dose using the measurements.
  • Glucose level control systems that autonomously determine a quantity of medicament (e.g., insulin or counter-regulator agent, such as Glucagon) to supply to a patient are becoming more common.
  • medicament e.g., insulin or counter-regulator agent, such as Glucagon
  • the use of glucose level control systems and medicament pumps free the patient from the inconvenience of injection therapy.
  • the automated closed-loop control algorithms are generally more accurate and provide better disease maintenance than other diabetes management options. For example, using test strips to measure glucose levels and performing injection therapy based on the test strips tends to be less accurate as it may not account for previously injected insulin or recent food consumption.
  • glucose level control system of the present disclosure can account for unusual activity, some glucose level control systems may not and/or the patient may not feel comfortable relying on the glucose level control system to account for the unusual activity.
  • patients also referred to as “subjects”
  • users e.g., parents, guardians, etc.
  • Closed loop or hybrid closed loop automated insulin delivery systems may use basal rates as a starting point from which insulin delivery is modulated. In some systems these may be entered manually or set autonomously. Embodiments of the present disclosure describe a system and method for adjusting these basal rates in order to optimize glucose control. Further, embodiments of the present disclosure describe a system and method for adjusting insulin (or other medicament) doses or dose rates (e.g., meal dose rates, corrective dose rates, etc.). [0117] In certain embodiments, a user can enter or adjust a basal rate or basal rate segment (e.g., daytime or nighttime basal rate). The adjusted rate may be used by a control algorithm to modulate delivery of insulin, or other medicament.
  • a basal rate or basal rate segment e.g., daytime or nighttime basal rate
  • the ability to have a user manually adjust the basal rate may be particularly useful for experienced users who want more control of their diabetes management.
  • Detailed descriptions and examples of systems and methods according to one or more illustrative embodiments of the present disclosure may be found, at least, in the section entitled Manual Control of an Autonomous Glucose Level Control System and also in FIGS. 41-42 herein.
  • components and functionality for supporting manual control of an autonomous glucose level control system may be configured and/or incorporated into the systems and devices described with respect to FIGS. 1-6.
  • a glucose level control system is used to control glucose level in a subject.
  • glucose level may comprise blood glucose level, or glucose level in other parts or fluids of the subject’s body.
  • glucose level may comprise a physiological glucose level of the subject that can be a concentration of glucose in subject’s blood or an interstitial fluid in part of the subject’s body (e.g., expressed in milligram per deciliter (mg/dl)).
  • Glucose level control systems (GLCSes) or glucose control systems which can be referred to herein as glucose level systems or glucose control systems, can include a controller configured to generate dose control signals for one or more glucose control agents that can be infused into the subject.
  • Glucose control agents can be delivered to a subject via subcutaneous injection, via intravenous injection, or via another suitable delivery method. In the case of glucose control therapy via an ambulatory medicament pump, subcutaneous injection is most common.
  • Glucose control agents may include regulatory agents that tend to decrease a glucose level (e.g., blood glucose level) of the subject, such as insulin and insulin analogs, and counter-regulatory agents that tend to increase a glucose level of the subject, such as glucagon or dextrose.
  • a glucose level control system configured to be used with two or more glucose control agents can generate a dose control signal for each of the agents. In some embodiments, a glucose level control system can generate a dose control signal for an agent even though the agent may not be available for dosing via a medicament pump connected to the subject.
  • a GLCS may include or can be connected to an ambulatory medicament pump (AMP).
  • An ambulatory medicament pump is a type of ambulatory medical device ("AMD"), which is sometimes referred to herein as an ambulatory device, an ambulatory medicament device, or a mobile ambulatory device.
  • ambulatory medical devices include ambulatory medicament pumps and other devices configured to be carried by a subject and to deliver therapy to the subject. Multiple AMDs are described herein. It should be understood that one or more of the embodiments described herein with respect to one AMD may be applicable to one or more of the other AMDs described herein.
  • a GLCS can include a therapy administration system and an AMD that is in communication with the therapy administration system.
  • the AMD may comprise an AMP.
  • a GLCS implements algorithms and medicament or glucose control functionality discussed herein to provide medicament or glucose control therapy without being connected to an AMD.
  • the GLCS can provide instructions or dose outputs that direct a user to administer medicament to provide glucose control therapy.
  • the user may use, for example, a medicament pen to manually or self-administer the medicament according the GLCS’s dose outputs.
  • the user may also provide inputs such as glucose level readings into the GLCS for the GLCS to provide dose outputs.
  • the user inputs into the GLCS may be in combination with inputs from other systems or devices such as sensors as discussed herein.
  • the GLCS can provide glucose control therapy based on user inputs without other system or device inputs.
  • the GLCS includes a memory that stores specific computer- executable instructions for generating a dose recommendation and/or a dose control signal.
  • the dose recommendation and/or the dose control signal can assist with glucose level control of a subject via medicament therapy.
  • the dose recommendation or dose output of the GLCS can direct a user to administer medicament to provide medicament therapy for glucose level control, including manual administration of medicament doses.
  • the GLCS includes the memory and a delivery device for delivering at least a portion of the medicament therapy.
  • the GLCS includes the memory, the delivery device, and a sensor configured to generate a glucose level signal. The GLCS can generate the dose recommendation and/or the dose control signal based at least in part on the glucose level signal.
  • the dose recommendation and/or the dose control signal can additionally be based at least in part on values of one or more control parameters.
  • Control parameters can include subject- specific parameters, delivery device-specific parameters, glucose sensor-specific parameters, demographic parameters, physiological parameters, other parameters that can affect the glucose level of the subject, or any combination of one or more of the foregoing.
  • the ambulatory medical device is an electrical stimulation device, and therapy delivery includes providing electrical stimulation to a subject.
  • An example of an electrical stimulation device is a cardiac pacemaker.
  • a cardiac pacemaker generates electrical stimulation of the cardiac muscle to control heart rhythms.
  • Another example of an electrical stimulation device is a deep brain stimulator to treat Parkinson’s disease or movement disorders.
  • FIG. 1A-FIG. 1C show examples of glucose level control systems that provide glucose level control via an ambulatory medical device or AMD, such as an ambulatory medicament pump (AMP), connected to a subject.
  • AMD ambulatory medical device
  • AMP ambulatory medicament pump
  • the AMD 100 is connected to an infusion site 102 using an infusion set 104.
  • the AMD 100 may include a medicament pump and an integrated user interface 106a that permit a user to view pump data and change therapy settings via user interaction with the user interface elements of the user interface 106a.
  • An analyte sensor 110 such as a glucose level sensor or a glucose sensor, generates a glucose level signal that is received by the glucose level control system.
  • the analyte sensor 110 can include an insulin level sensor that can generate an insulin level signal that can be received by the glucose level control system.
  • the analyte senor 110 can include a glucose level sensor and/or an insulin level sensor.
  • the analyte senor 110 may include a continuous glucose monitor (CGM).
  • CGM continuous glucose monitor
  • the glucose level control system includes the AMD 100 (e.g., a medicament pump) communicates with an external electronic device 108 (such as, for example, a smartphone) via a wireless data connection. At least some of the pump controls can be manipulated via user interaction with user interface elements in the user interface 160b of the external electronic device 108.
  • the glucose level sensor 110 can also communicate with the AMD 100 (that includes a medicament pump) via a wireless data connection.
  • Example user interfaces that can be implemented by one or more of the external electronic device 108, the AMD 100, a remote electronic device (not shown), and/or other electronic devices are shown and described in PCT Patent Application Publication Nos. WO 2021/067767 and WO 2021/011699, the entire contents of which are hereby incorporated by reference herein and made a part of this specification.
  • the AMD 100 (e.g., a medicament pump) includes an integrated cannula that inserts into the infusion site 102 without a separate infusion set.
  • At least some of the pump controls can be manipulated via user interaction with user interface elements 106b of an external electronic device 108.
  • pump controls can be manipulated via user interaction with user interface elements generated by a remote computing environment (not shown), such as, for example, a cloud computing service, that connects to the AMD 100 (medicament pump) via a direct or indirect electronic data connection.
  • Glucose level control systems typically include a user interface configured to provide one or more of therapy information, glucose level information, and/or therapy control elements capable of changing therapy settings via user interaction with interface control s.
  • the user can provide an indication of the amount of the manual bolus of medicament from an electronic device remote from the medicament pump.
  • the user interface can be implemented via an electronic device that includes a display and one or more buttons, switches, dials, capacitive touch interfaces, or touchscreen interfaces, or voice interfaces.
  • at least a portion of the user interface is integrated with an ambulatory medicament pump that can be tethered to a body of a subject via an infusion set configured to facilitate subcutaneous injection of one or more glucose control agents.
  • at least a portion of the user interface is implemented via an electronic device separate from the ambulatory medicament pump, such as a smartphone.
  • FIGS. 2A-2D illustrate block diagrams showing example configurations of four embodiments (200a/200b/200c/200d) of a glucose level control system.
  • a glucose level control system 200a may comprise an ambulatory medical device (AMD) 100 that includes a controller 202a having an electronic processor 204a and a memory 210a that stores instructions 208a executable by the electronic processor 204a.
  • the controller 202a and a pump 212 e.g., a medicament pump
  • the pump 212 can be integrated into AMD 100.
  • the pump 212 can be an infusion pump for administering regulatory agent and/or counter- regulatory agent.
  • the AMD 100 can include at least one pump 212.
  • the AMD 100 may include at least one pump and a wireless connection interface or a transceiver.
  • the AMD 100 can include a wireless electronic communications interface (e.g., the transceiver 214a) for wireless data (e.g., digital data) communications with external electronic devices.
  • the controller 202a can implement at least a portion of a control algorithm that generates dose control signals for one or more glucose control agents based on time-varying glucose levels of the subject (e.g., received from a glucose level sensor 110 that is in communication with the AMP 100) and one or more control parameters.
  • the dose control signals when delivered to the pump 212, result in dosing operations that control a glucose level of the subject.
  • the pump 212 may be controlled by at least one pump controller.
  • the pump controller may be included in the pump 212.
  • the pump controller receives the dose control signals and controls the operation of the pump 212 based on the received dose control signals.
  • the pump controller may be integrated with the pump.
  • the controller may be included in the AMP 100, or in an external electronic device 108 or a remote computer 206, that are connected to the AMP 100 via wired or wireless communication links.
  • a glucose level control system may comprise an ambulatory medicament pump AMP 100 (also referred to as ambulatory medicament pump or AMP) that includes a medicament pump, and at least one controller that controls the medicament pump.
  • the controller may be included in the AMD 100, or in an external electronic device 108 or a remote computer 206, that are connected to the AMD 100 via wired or wireless communication links.
  • a glucose level control system 200b can operate at least partially via execution of instructions 208b by an electronic processor 204b of an external electronic device 108 separate from the AMD 100.
  • the external electronic device 108 can include a transceiver 214b capable of establishing a wireless data connection to the AMD 100, and a controller 202b can implement at least a portion of a control algorithm via execution of instructions 208b stored in memory 210b.
  • the controller 202b can implement at least a portion of a control algorithm that generates dose control signals for one or more glucose control agents based on time-varying glucose levels of the subject and one or more control parameters.
  • the dose control signals when delivered to the pump controller of the pump 212, result in dosing operations that control the glucose level of a subject.
  • the dose control signals are transmitted from the electronic device transceiver 214b to the AMD transceiver 214a over a short-range wireless data connection 216.
  • the AMD 100 receives the dose control signals and passes them to the pump controller of the pump 212 for dosing operations.
  • a glucose level control system 200c may include a remote computer 206 that is in communication with the AMD 100 (e.g., an ambulatory medicament pump).
  • the glucose level control system 200c can operate at least partially via execution of instructions 208c by an electronic processor 204c integrated with the remote computer 206, such as, for example, a cloud service (e.g., remote computing environment).
  • the controller 202c can implement at least a portion of a control algorithm that generates dose control signals for one or more glucose control agents based on time-varying glucose levels of the subject and one or more control parameters.
  • the dose control signals when received by the pump controller of the pump 212, may result in dosing operations that control the glucose level of a subject.
  • the dose control signals are transmitted from the remote computer 206 from wide area network (WAN) connection interface of the remote computer 206 (e.g., WAN connection interface 220c) to a WAN connection (e.g., WAN connection interface 220a) of the AMD 100 over an end-to-end wireless data connection 218.
  • WAN wide area network
  • the AMD 100 receives the dose control signals and passes them to the pump 212 (or the controller that controls the pump 212) for dosing operations.
  • a glucose level control system 200d that includes a remote computer 206 that is in communication with an external electronic device 108 (e.g., an electronic device of the subject), and the AMD 100, which is in communication with the electronic device 108.
  • the glucose level control system 200d can have two or more controllers 202a, 202b, 202c (e.g., located in different subsystems) that cooperate to generate a dose control signal for dosing operations by the pump 212.
  • the remote computer 206 can transmit or receive data or instructions passed through a WAN connection interface 220c via an end-to-end wireless data connection 218 to a WAN connection interface 220b of the external electronic device 108.
  • the external electronic device 108 can transmit or receive data or instructions passed through a transceiver 214b via a short- range wireless data connection 216 to a transceiver 214a of an AMD 100.
  • the electronic device 108 can be omitted, and the controllers 202a, 202c of the AMD 100 and the remote computer 206 cooperate to generate dose control signals that are passed to the pump 212 (or the pump controller that controls pump 212).
  • the AMD 100 may have its own WAN connection interface to support a direct end-to-end wireless data connection to the remote computer 206.
  • a glucose level control system 200 may include circuitry that implements an electronic communications interface (ECI) 302 configured to send and receive electronic data from one or more electronic devices.
  • ECI includes a sensor interface 304 (e.g., a glucose sensor interface) configured to receive a glucose level signal from a sensor 110 (e.g., an analyte sensor or a glucose level sensor) such as a continuous glucose monitor (CGM).
  • a sensor 110 e.g., an analyte sensor or a glucose level sensor
  • CGM continuous glucose monitor
  • the sensor 110 can be a continuous glucose monitor (CGM).
  • Some CGMs may generate glucose level signals at fixed or periodic measurement intervals, such as five-minute intervals.
  • the sensor 110 can be operatively connected to a subject in order to generate a glucose level signal that corresponds to a glucose level estimate or measurement of the subject.
  • the glucose level signal can be used by the controller 202b to generate a dose control signal.
  • the dose control signal can be provided to a pump 212 via a pump interface 306 (or a delivery device interface or an infusion motor interface).
  • the sensor interface 304 connects to the sensor 110 via a short-range wireless connection 308.
  • the pump interface 306 connects to the pump 212 via a short-range wireless connection 310.
  • the pump interface 306 connects to the pump 212 via a local data bus, such as when the controller 202b, the ECI 302, and the pump 212 are integrated into an AMD 100.
  • the sensor 110 can be an insulin level sensor that can detect insulin levels.
  • the sensor interface 304 can be configured to receive an insulin level signal from the sensor 110, which can correspond to an insulin level estimate or measurement of the subject (e.g., a concentration of insulin in subject's blood).
  • the insulin level signal can be used by the controller 202b to generate a dose control signal, which can be provided to the pump 212 via the pump interface 306.
  • the sensor 110 can include a glucose sensor and an insulin sensor.
  • the controller 202b can be configured to generate the dose control signal using a control algorithm that generates at least one of a basal dose, a correction dose, and/or a meal dose (or food intake).
  • a control algorithm that generates at least one of a basal dose, a correction dose, and/or a meal dose (or food intake). Examples of some control algorithms that can be used to generate these doses are disclosed in U.S. Patent Application Publication Nos. 2008/0208113, 2013/0245547, 2016/0331898, and 2018/0220942 (referenced herein as the “Controller Disclosures”), or in the PCT Patent Application Publication No. WO 2021/067856, the entire contents of which are incorporated by reference herein and made a part of this specification.
  • the correction dose can include regulatory or counter-regulatory agent and can be generated using a model-predictive control (MPC) algorithm and/or other algorithms such as those disclosed in the Controller Disclosures.
  • the basal dose can include regulatory agent and can be generated using a basal control algorithm such as disclosed in the Controller Disclosures.
  • the meal dose can include regulatory agent and can be generated using a meal control algorithm such as disclosed in the Controller Disclosures. In some cases, a meal dose can be generated by the subject via a user interface of the glucose level control system 200a/200b/200c/200d. Additional aspects and improvements for at least some of these controllers are disclosed herein.
  • the dose control signal can be transmitted to pump 212 via the ECI 302 or can be transmitted to the pump 212 via an electrical conductor when the controller 202b is integrated in the same housing as the pump 212, such as discussed herein for controller 202a.
  • FIG. 4A shows a block diagram of an example glucose level control system in online operation mode.
  • the controller 400 can be configured to operate in “online mode” (or “automatic mode”) during time periods when the controller 400 receives a glucose level signal 402 from the sensor 110 (e.g., a glucose level sensor) and/or an insulin level signal 402 from the sensor 110 (e.g., an insulin level sensor).
  • the control algorithm In online mode, the control algorithm generates a dose control signal 404 that implements regular correction doses based on values of the glucose level signal 402 and/or insulin level signal 402 and control parameters of the control algorithm.
  • the pump 212 is configured to deliver at least correction doses and basal doses to the subject without substantial user intervention while the controller 400 remains in online mode.
  • the ambulatory medicament pump 212 can include one or more medicament cartridges or can have an integrated reservoir 408 of medicament.
  • the reservoir 408 may be integrated with the pump 212.
  • a medicament stored in the reservoir 408 can be delivered to the subject by operation of the pump 212.
  • a pump motor of the pump 212 can direct medicament for infusion in response to one or more dose control signals as discussed herein.
  • the operation of the pump 212 can be controlled by the controller 400.
  • the controller 400 may generate the dose control signal 404 using a control scheme such as described in U.S. Patent No. 7,806,854, the contents of which are hereby incorporated by reference in its entirety herein.
  • FIG. 4B shows a block diagram of an example glucose level control system in offline operation mode.
  • the controller 400 can be configured to operate in “offline mode” during time periods when the controller does not receive a glucose level signal 402 and/or insulin level signal 402 from a sensor 110, at least during periods when the glucose level signal 402 is expected but not received. Additionally, the controller 400 may operate in “offline mode” during time periods when one or more glucose level signals received from the sensor 402 are identified as artifacts (e.g., suspected artifacts). In the offline mode, the controller may generate dose control signals as described in U.S. Patent No. 10,543,313, the entire contents of which are hereby incorporated by reference in its entirety herein.
  • the control algorithm In offline mode, the control algorithm generates a dose control signal 404 that implements correction doses in response to isolated glucose measurements 406 (such as, for example, measurements obtained from the subject using glucose test strips) and/or insulin measurements 406 and based on control parameters of the control algorithm.
  • the pump 212 is configured to deliver basal doses to the subject without substantial user intervention and can deliver correction doses to the subject in response to isolated glucose measurements 406 and/or isolated insulin measurements 406 while the controller 400 remains in offline mode.
  • FIG. 5 illustrates an automated glucose level control system 510 for regulating the glucose level of an animal subject (subject) 512, which may be a human.
  • the automated glucose level control system 510 is an example of a medicament infusion system and may include any of the embodiments described herein with respect to medicament infusion systems.
  • the subject 512 may receive doses of insulin from one or more delivery devices 514, for example infusion pump(s) coupled by catheter(s) to a subcutaneous space of the subject 512.
  • the delivery devices 514 may also deliver a counter-regulatory agent or hyperglycemic agent, such as glucagon or dextrose, for control of the glucose level under certain circumstances.
  • a counter-regulatory agent such as glucagon or dextrose
  • the delivery devices 514 may be mechanically driven infusion mechanisms having dual cartridges for insulin and the counter -regulatory agent, respectively.
  • insulin herein is to be understood as encompassing all forms of insulin - like substances including natural human or animal insulin as well as synthetic insulin in any of a variety of forms (commonly referred to as “insulin analogs”).
  • a glucose sensor 516 is operatively coupled to the subject 512 to continuously or continually sample a glucose level of the subject 512.
  • the glucose sensor 516 may be referred to as a continuous glucose monitoring (CGM) sensor, which may continuously or periodically (continually) measure or sense glucose levels of the subject 512 for at least a period of time. Sensing may be accomplished in a variety of ways, generally involving some form of physical coupling 521 between the subject 512 and the glucose sensor 516.
  • a controller 518 may control operation of the delivery device(s) 514 as a function of a glucose level signal 519 from the glucose sensor 516 and subject to programmed input parameters (P ARAMS) 520 which may be provided by a user such as the subject 512, a parent or guardian of the subject 512, or a healthcare provider (e.g., a clinician or doctor).
  • P ARAMS programmed input parameters
  • One input parameter for automatic operation may include the weight of the subject 512.
  • the glucose level control system 510 can provide effective automated control without receiving explicit information regarding either meals that the subject 512 has ingested or any other “feedforward” information, which is achieved in part by an adaptive aspect to operation of the controller 518.
  • the glucose level control system 510 can use received information regarding either meals that the subject ingested, or plans to ingest, or other “feedforward” information to modify control of blood glucose and/or delivery of insulin or counter-regulatory agent.
  • the controller 518 is an electrical device with control circuitry that provides operating functionality as described herein.
  • the controller 518 may be realized as a computerized device (e.g., a hardware processor) having computer instruction processing circuitry that executes one or more computer programs each including respective sets of computer instructions.
  • the processing circuitry will generally include one or more processors 530 along with memory 540 and input/output circuitry 532 coupled to or in communication with the processor(s) 530, where the memory 540 stores computer program instructions and data, and the input/output circuitry 532 can provide interface(s) to external devices such as the glucose sensor 516 and delivery device(s) 514.
  • the input/output circuitry 532 may provide a user interface, or may operate with one or more processors (e.g., the controller 518 or a separate processor 530 included in the glucose level control system 510 or in a separate computing system, such as a smartphone, a laptop computer, a desktop computer, a smartwatch, and the like) to provide a user interface to a user (e.g., the subject 512, a parent or guardian, or a clinician).
  • the input/output circuitry 532 may include a touchscreen and/or a touchscreen controller 538 configured to control a touchscreen (not shown).
  • the controller 518 may perform all of the functionality of the glucose level control system 510.
  • the processor 530 may be optional or omitted.
  • the controller 518 may perform at least automated glucose level control of the subject 512, and one or more separate processors 530 may perform one or more additional operations of the glucose level control system 510 (or medicament pump), such as tracking occurrences of hyperglycemic or hypoglycemic events or risk events, outputting data to a user, controlling or initiating communication with another computing system, regulating access to the glucose level control system 510, or other operations unrelated to operation of a medicament pump or the delivery devices 514.
  • the input/output circuitry 532 may control communication with one or more other computing systems and/or with a user.
  • the input/output circuitry 532 may include one or more separate interface circuits or controllers to facilitate user interaction and/or communication.
  • the input/output circuitry 532 may include user interface circuitry 534, network interface circuitry 536, and/or a touchscreen controller 538.
  • the user interface circuitry 534 may include any circuitry or processors that may output a user interface to a user and/or receive user input from the user via the user interface.
  • the user interface circuitry 534 may receive one or more signals from a processor 530 corresponding to a user interface.
  • the user interface circuitry 534 may control a display to present the user interface to a user based on the one or more signals received from the processor 530.
  • the user interface circuitry 534 may include any circuitry that can receive a signal corresponding to an interaction by a user with a user interface and can provide the signal to the processor 530 and/or controller 518 for further processing.
  • the user interface circuitry may be replaced by a touchscreen controller 538 that can control a touchscreen interface. In other cases, the touchscreen controller 538 may be in addition to the user interface circuitry 534.
  • the network interface circuitry 536 may include any circuitry that enables communication with a wired or wireless network.
  • the network interface circuitry 536 may include one or more network interface cards and/or wireless radios (e.g., a Bluetooth radio, a Bluetooth Low Energy (BLE) radio, a 4g LTE radio, a 5G radio, a ND-LTE radio, and the like).
  • wireless radios e.g., a Bluetooth radio, a Bluetooth Low Energy (BLE) radio, a 4g LTE radio, a 5G radio, a ND-LTE radio, and the like.
  • the memory 540 can include non-volatile memory and/or volatile memory.
  • the non volatile memory may include flash memory or solid-state memory.
  • the control system 510 is also able to operate in an offline manner in which it is used to provide delivery of insulin (and potentially glucagon as well), independent of or without receipt of glucose levels reported by the sensor 516.
  • the glucose level control system 510 may operate in an offline manner without input from the sensor 516.
  • overall operation may be divided between online periods each including a succession of sampling intervals when a glucose level signal 519 is available, and offline periods each including a succession of sampling intervals when the glucose level signal 519 is either completely or intermittently unavailable.
  • online and “offline” for these periods.
  • offline operation may be user-selected for some reason even when a glucose level signal 519 is available for use.
  • User control inputs may be provided via a local or remote user interface of some type.
  • the user interface may resemble that of conventional insulin pumps or similar devices, e.g., by including control buttons for commanding the delivery of a bolus and perhaps a small display.
  • the system may have a wired or wireless interface to a remote device that may incorporate a fuller-function user interface, such as a smartphone, smartwatch, laptop computer, desktop computer, cloud computing service, or other wearable device or computing device.
  • the wireless interface may provide access to a local area network, such as a personal home network, a company network, or otherwise.
  • the wireless interface may provide a direct connection between local devices available to a user (e.g., via Bluetooth or other near field communication technologies).
  • the wireless interface may provide access to a wide area network, such as, but not limited to, the Internet.
  • the wireless interface may include a cellular interface that permits access to a network via a 4G or 5G cellular connection.
  • the cellular interface may be a low power interface, such as narrowband LTE or other Internet of Things (IoT) interfaces.
  • IoT Internet of Things
  • a user may provide one or more blood glucose measurements to the control system 510 to facilitate automatic operation of the control system 510. These measurements may be provided over a particular time period. Alternatively, or in addition, the glucose level control system 510 may use a therapy history and/or a history of prior glucose level control measurements to facilitate automatic operation of the control system 510 for at least a particular time period.
  • the description herein refers to a “user” as the source of the user control inputs 523.
  • the “user” as used herein may be the subject 512, a parent or guardian of the subject 512, a healthcare provider (e.g., a clinician, doctor, or other person who may provide medical care to the subject), or any other user who may be authorized to help manage therapy of the subject 512.
  • the glucose level control system 510 is a personal device worn by a subject 512 for continual glucose control.
  • the user and subject 512 may be the same person.
  • there may be another person involved in the care of the subject 512 and providing control input and in such implementations, that other person has the role of user.
  • FIG. 6 shows an example structure of the controller 518 in accordance with certain embodiments.
  • the controller 518 illustrated in FIG. 6 may represent a physical structure with different controllers or processors, or a logical structure that is implemented by one or more physical processors.
  • a single processor may be used to implement each of the controllers illustrated in FIG. 6, each controller may be implemented by its own processor, or certain processors may implement multiple, but not necessarily all, of the controllers illustrated in FIG. 6 as part of the controller 518.
  • the controllers of FIG. 6 are illustrated as part of the controller 518, in some implementations, one or more of the controllers may be separate from the controller 518.
  • the controller 518 may include four separate controllers, namely a glucagon (or counter-regulatory agent) controller 622, a basal controller 624, a corrective insulin controller 626 (or model predictive controller), and a priming insulin controller 628 (or meal controller).
  • the basal controller 624 includes a nominal rate controller 630 and a modulating controller 632.
  • the glucagon controller 622 generates a glucagon dose control signal 634 provided to a glucagon delivery device 514-1.
  • Respective outputs 636-640 from the controllers 624, 626, 628 may be combined to form an overall insulin dose control signal 642 provided to insulin delivery device(s) 514-2.
  • the output signal 636 from the basal controller 624 may be formed by a combination of respective outputs of the nominal rate controller 630 and a modulating controller 632.
  • the insulin delivery device(s) 514-2 may include devices tailored to deliver different types and/or quantities of insulin, and the exact configuration may be known to and/or under the control of the controllers 624-628.
  • the collection of one or more insulin delivery devices 514-2 is referred below to in the singular as an insulin delivery device 514-2.
  • input/output signals of the various controllers including the glucose level signal 519, input parameters 520 and user control inputs 523 as well as a set of inter-controller signals 644.
  • the inter-controller signals 644 enable communication of information from one controller, where the information is developed or generated, to another controller where the information may be used for that controller's control function.
  • the controllers 622, 624, 626, 628 may be operated in either the online/automatic mode or in the offline mode.
  • the corrective insulin controller 626 regulates glucose level using a control scheme such as described in US Patent No. 7,806,854, the contents of which are hereby incorporated by reference in its entirety herein.
  • the basal controller 624 and priming insulin controller 628 may perform adaptive automated control as described in International Patent Application Publication WO 2012/058694 A2, the contents of which are hereby incorporated by reference in its entirety herein.
  • the controllers 622, 624, 626, 628 generally employ control methods or algorithms that include control parameters that are mathematically combined with reported glucose values to generate an output value that is converted (either directly or via additional conditioning) into the dose control signals 634, 642.
  • the control scheme described in US Patent No. 7,806,854 includes a generalized predictive control (GPC) method that incorporates a variety of control parameters.
  • the control algorithms are generally adaptive, meaning that control parameters are dynamically adjusted during operation to reflect changing operating circumstances and a “learning” aspect — by monitoring its own operation, the algorithm adjusts its operation to be more specifically tailored to the individual user, enhancing the algorithm's effectiveness and reducing or avoiding a need for additional explicit input information about the user.
  • the input parameters 520 may form part of the control parameters used by the control algorithm.
  • Other control parameters are internal parameters according to the specifics of the algorithm, and selected ones of those internal control parameters are dynamically adjusted to realize the adaptation of the control algorithm.
  • One feature of operation is the ability of the controllers to learn from recent past periods of online operation and to use that learning during offline operation.
  • a second method automatically calculates the correct size of a meal bolus of insulin and administers it in response to a user control input. Both methods utilize information obtained during past periods of online operation to automatically calculate correct values, freeing the user of a need to make the calculation or provide a correction factor.
  • Hyperglycemia is a condition that occurs when the levels of sugar or glucose in the blood exceeds a particular level (e.g., 180 mg/dL). This condition may occur in diabetics.
  • a subject may use an automated glucose level control system, which may automatically provide insulin to a subject using a medicament pump. The administered insulin may help control the glucose level of the subject by consuming glucose in the subject.
  • Hypoglycemia is a condition that occurs when the levels of sugar or glucose in the blood are below a particular level (e.g., 70 mg/dL). This condition may have adverse consequences including loss of consciousness, seizures, and death.
  • the levels of blood sugar that lead to hyperglycemia and hypoglycemia may vary from patient to patient.
  • a subject may consume carbohydrates to increase blood sugar. Because of the severe consequences associated with a hypoglycemic event, subjects usually consume carbohydrates that metabolize quickly. These carbohydrates are often unhealthy but are preferable to the occurrence of a hypoglycemic event.
  • the carbohydrates may include candy bars with a lot of refined sugar.
  • a bi-hormonal glucose-control system may reduce the risk of occurrence of hypoglycemia by including, in addition to insulin, a counter-regulatory agent (e.g., Glucagon) that can be administered to a subject when the glucose level drops too low (e.g., below 50 mg/dL).
  • a counter-regulatory agent e.g., Glucagon
  • understanding the amount of carbohydrate therapy consumed or avoided can be important in monitoring the subject’s nutrition intake. While monitoring nutrition in take is important for all people, it is particularly important for diabetics because diabetics must balance eating healthy with ensuring that their blood sugar is maintained in a particular range to avoid both hyperglycemia and hypoglycemia.
  • the present disclosure relates to a system that can perform a computer-implemented method of generating an indication of total carbohydrate therapy over a time period in a subject using a medicament pump configured to deliver at least insulin therapy to the subject.
  • the system may be an automated glucose level control system (e.g., the glucose level control system 510) that includes a hardware processor (e.g., controllers 518) for determining dose control signals to provide the medicament pump (e.g., delivery devices 514).
  • the medicament pump may be configured to deliver both insulin therapy and counter- regulatory agent (e.g., Glucagon) therapy.
  • the system may be separate from the glucose level control system but may receive blood glucose information from the glucose level control system.
  • the system may be personal computing system or a cloud computing system that can received blood glucose information from the glucose level control system.
  • the system may receive or determine a glucose level of a subject (e.g., subject 512).
  • the glucose level of the subject may be determined based on a signal (e.g., a glucose level signal) received from a continuous glucose monitoring (CGM) sensor (e.g., glucose sensor 516) that corresponds to the glucose level of the subject.
  • CGM continuous glucose monitoring
  • the glucose level may be determined from an isolated glucose measurement, such as may be obtained using a glucose measurement kit and/or glucose paper.
  • the system can determine whether a triggering event for raising the subject’s glucose level has occurred.
  • the triggering event may include a glucose level that indicates an occurrence of a hypoglycemic event or a risk of the occurrence of a hypoglycemic event exceeding a risk threshold within a particular period of time.
  • a risk of a hypoglycemic event may be determined when a glucose level of the subject falls below a glucose threshold. This glucose threshold may vary for different subjects and may, in some cases, be specified by the subject or a caregiver (e.g., healthcare provider, parent, or guardian).
  • the system may determine an amount of counter- regulatory agent to administer, or an amount of counter-regulatory agent that would be administered if the glucose level control system included the capability of administering a counter-regulatory agent.
  • the counter-regulatory agent is administered by, for example, the automated glucose level control system.
  • the counter-regulatory agent is not administered.
  • the automated glucose level control system may not be capable of delivering the counter-regulatory agent.
  • the automated glucose level control system may be capable of delivering the counter-regulatory agent but may not have a dose of the counter-regulatory agent available.
  • the system can use the indication of the counter-regulatory agent that is administered or that would be administered to determine a corresponding amount of carbohydrates.
  • the corresponding amount of carbohydrates may be indicative of the amount of carbohydrates that were consumed to prevent the hypoglycemic event, to reduce the risk of the hypoglycemic event, or in response to an occurrence of a hypoglycemic event.
  • the corresponding amount of carbohydrates may be indicative of the amount of carbohydrates that would have been consumed if the counter-regulatory agent were not available.
  • the corresponding amount of carbohydrates may be obtained from a mapping between amounts of a counter-regulatory agent and amounts of carbohydrates.
  • the mapping may be based on a measured equivalency between carbohydrates and a counter- regulatory agent.
  • the mapping may be between a determined amount of counter-regulatory agent and an amount of carbohydrate a subject indicates he or she normally consumes when determining that a hypoglycemic event may occur.
  • the mapping may be implemented by a lookup table that maps different amounts of counter-regulatory agent to different corresponding amounts of carbohydrates.
  • a single quantity of counter-regulatory agent may map to different amounts of carbohydrates depending on the type of carbohydrate consumed (e.g., simple vs complex carbohydrates, or the type of candy bar consumed, etc.).
  • the mapping may be based on a formula that converts an amount of counter-regulatory agent to an amount of carbohydrates based on a correspondence between the amount of counter-regulatory agent and the amount of carbohydrates.
  • the determination of a relationship between the counter -regulatory agent and carbohydrates may be based on clinical tests comparing carbohydrates to the counter - regulatory agent (e.g., Glucagon, dextrose, etc.). Further, the mapping may be based at least in part on a subject’s preferred carbohydrate source and/or characteristics of the subject (e.g., weight).
  • the system can track a number of hypoglycemic events or a number of occurrences of a trigger indicating an impending risk of a hypoglycemic event within a particular time period.
  • the time period may be days, weeks, months, years, or any other period of time over which it is desirable to determine a relationship between carbohydrates consumed or avoided based on the lack of availability or availability of a counter -regulatory agent.
  • the tracking of carbohydrate therapy may be based on a number of hypoglycemia events or hypoglycemia risk events instead of or in addition to a time period.
  • the system can determine an estimate of the carbohydrate therapy saved or that would have been saved by having access to the counter - therapy agent.
  • the system can generate a report for the time period that indicates the total carbohydrate saved or that would have been saved with access to counter -regulatory agent.
  • the report may include an aggregate or sum of the carbohydrate therapy required or saved during the time period. This time period may be days, weeks, months, years, or since a particular time (e.g., since the subject starting using the system).
  • the report may indicate the type of carbohydrates typically consumed by the subj ect when responding to a hypoglycemic event or a risk of an impending hypoglycemic event.
  • This report can be presented to the subject, a healthcare provider, and/or a parent or guardian of the subject.
  • the healthcare provider can use this report to help care for the subject.
  • the healthcare provider can use the report to generate a nutrition plan for the subject that accounts for the carbohydrates consumed to maintain the glucose level within a desired or setpoint range.
  • the report may include a range of carbohydrate therapy avoided or likely consumed to address the risk of hypoglycemia events.
  • the report may include an amount of calories saved or not consumed, an amount of sugar avoided, an amount of food not consumed, a likely weight gain avoided, etc. based on the use of a counter-regulatory agent in place of carbohydrate therapy.
  • FIG. 7 presents a flowchart of an example carbohydrate therapy equivalence tracking process 700 in accordance with certain embodiments.
  • the process 700 may be performed by any system that can track the glucose level of a subject over time and identify hypoglycemic events, or occurrences when a risk of a hypoglycemic event satisfies a threshold (e.g., when the risk of the hypoglycemic event matches or is above a particular probability).
  • the process 700 may be performed by one or more elements of the glucose level control system 510.
  • At least certain operations of the process 700 may be performed by a separate computing system that receives indications of glucose levels of the subject 512 from the glucose level control system 510 and/or indications of hypoglycemic events (or identified above threshold hypoglycemic risk events).
  • a separate computing system that receives indications of glucose levels of the subject 512 from the glucose level control system 510 and/or indications of hypoglycemic events (or identified above threshold hypoglycemic risk events).
  • the process 700 begins at block 702 where the glucose level control system 510 receives a glucose level of a subject 512.
  • Receiving the glucose level may include receiving a glucose level signal corresponding to a glucose level of the subject.
  • the glucose level signal may be received from the glucose sensor 516 (e.g., a CGM sensor).
  • the glucose level may be received from a user that provides the glucose level to the glucose level control system 510 via a user interface, such as a user interface generated by the processor 530 that may be output on a touchscreen by the touchscreen controller 538.
  • the glucose level received from the user may be a glucose level measured using an alternative sensor or measurement mechanism (e.g., diabetes measurement strips) that may be used in place of the glucose sensor 516.
  • the glucose level control system 510 determines based at least in part on one or more of the glucose level or an indication from a different sensor that a triggering event for raising the glucose level of the subject 512 has occurred.
  • the triggering event may include a determination that a hypoglycemic event or an episode of hypoglycemia is present or is occurring in the subject 512.
  • the triggering event may include a determination that there is an impending risk of hypoglycemia in the subject 512, or an impending risk that a hypoglycemic event will occur within a particular amount of time in the subject 512.
  • the triggering event may occur in response to the triggering of a hypoglycemic event criterion, described herein.
  • a hypoglycemic event criterion can include, for example, determining that the glucose level signal indicates carbohydrate treatment by the subject and/or that a physiological sensor (e.g., a heartrate sensor, a breath rate sensor, a blood pressure sensor, etc.) other than the glucose sensor indicates carbohydrate treatment by the subject.
  • a physiological sensor e.g., a heartrate sensor, a breath rate sensor, a blood pressure sensor, etc.
  • the determination of the hypoglycemic event or the risk of a hypoglycemic event occurring may be determined by comparing the glucose level of the subject to a glucose threshold.
  • the determination of the hypoglycemic event or the risk of a hypoglycemic event occurring may be determined by comparing a trend and/or rate of change (e.g., rate of decrease) in the glucose level to a threshold.
  • the particular glucose level and the trend in the glucose level may be combined to determine a risk of hypoglycemia. For example, if the glucose level is low (e.g., below a particular threshold, such as 60 mg/dL), but a determined trend in the glucose level is upwards, then a risk of hypoglycemia may be lower than if the glucose level is above the threshold, but the determined trend in the glucose level is downwards towards a threshold.
  • the threshold(s) used to determine whether a hypoglycemic event is occurring or to determine that there is an above threshold risk of hypoglycemia occurring may vary based on physiological characteristics of the subject 512.
  • the physiological characteristics may be based on physiological characteristics associated or shared among groups of patients (e.g., gender, age, weight) or may be specific to the particular subject 512.
  • thresholds associated with a risk of hypoglycemia may be determined based on determined glucose levels of the subject 512 during prior occurrences of hypoglycemia as determined by the glucose level control system 510 or based on clinical data specific to the subject 512.
  • the glucose level control system 510 determines an amount of counter-regulatory agent at block 706.
  • the glucose level control system 510 may determine the amount of counter-regulatory agent based at least in part on the glucose level of the subject 512, the amount or percentage of risk of hypoglycemia occurring (e.g., a 99% risk or probability of hypoglycemia may trigger a larger counter- regulatory agent dose than a 75% risk or probability of hypoglycemia), physiological characteristics of the subject 512, a trend in the glucose level of the subject 512, or a type of counter-regulatory agent.
  • the glucose level control system 510 may use a delivery device 514- 1 to deliver the determined amount of counter-regulatory agent to the subject 512.
  • the counter-regulatory agent may be delivered to the subject 512 in response to the impending risk of hypoglycemia or the episode of hypoglycemia, and/or in response to the glucose level satisfying or falling below a threshold glucose level.
  • the threshold glucose level or the determination of whether to deliver the counter-regulatory agent may be based on physiological characteristics of the subject 512 and/or the risk tolerance of the subject 512 to a hypoglycemic event. It should be understood that, in the present context, risk tolerance generally does not refer to a user’s subjective propensity for risk.
  • the risk tolerance is typically an objective determination of how likely the subject 512 is to have a hypoglycemic event, or for symptoms of hypoglycemia to occur, when the glucose level of the subject 512 is at a particular level.
  • This risk tolerance may be determined based on a history of hypoglycemia, or lack thereof, in the subject 512 at particular glucose levels and/or based on clinical data obtained for the subject 512.
  • the glucose level control system 510 may stop delivery of insulin and implement other intervention methods as discussed herein in response to a hypoglycemic event or a risk of a hypoglycemic event.
  • the glucose level control system 510 may not deliver counter- regulatory agent to the subject 512 because, for example, the glucose level control system 510 may not be capable of delivering counter-regulatory agent or because the cartridge holding the counter-regulatory agent may be empty or have less than a threshold amount of counter- regulatory agent remaining.
  • the glucose level control system 510 determines a dose of carbohydrate therapy based at least in part on the counter-regulatory agent.
  • the carbohydrate therapy may refer to carbohydrates consumed to prevent or respond to an occurrence of hypoglycemia.
  • the carbohydrates may include any type of carbohydrate that the subject 512 may consume to prevent or respond to an occurrence of hypoglycemia, and typically includes fast-acting carbohydrates, which may include sugary foods that are easily converted into sugars in the human body.
  • the carbohydrate may be a candy bar, soda, fruit juice, or other foods that may have a lot of sugar or refined sugars.
  • Determining the dose of carbohydrate therapy may include accessing a mapping between the counter-regulatory agent and carbohydrates. This mapping may be stored in, and accessed from, the memory 540 and/or may be accessed from another computing device.
  • the glucose level control system 510 may determine the dose of carbohydrate therapy based at least in part on the mapping and the amount of the counter-regulatory agent. In some cases, the mapping may vary based on the type of counter -regulatory agent and/or the type of carbohydrates.
  • the type of counter-regulatory agent may be identified by a user or may automatically be determined based on a medicament cartridge installed or inserted into the glucose level control system 510.
  • the type of carbohydrates may be specified by a user and may include an identity of the type of carbohydrates usually consumed by the subject 512 when responding to an occurrence or a risk of an occurrence of hypoglycemia.
  • the user may specify, via a user interface, whether the subject usually consumes a candy bar or fruit juice, or the size of the carbohydrate usually consumed when responding to an occurrence or a risk of an occurrence of hypoglycemia.
  • the mapping between the counter-regulatory agent and carbohydrates may be generated based on a clinical comparison of the counter -regulatory agent to the carbohydrates. Alternatively, or in addition, the mapping may be based at least in part on a physiological characteristic of the subject 512.
  • the mapping may be stored in a lookup table or other data structure that can store relationships between different carbohydrates and counter-regulatory agents.
  • the mapping may be between different quantities and/or types of carbohydrates and different quantities and/or types of counter-regulatory agent.
  • the mapping may be a formula that relates the carbohydrates to the counter-regulatory agent or vice versa.
  • the glucose level control system 510 may use the determined amount of counter- regulatory agent as an index to a lookup table to determine a corresponding quantity of carbohydrates.
  • the glucose level control system 510 may apply the determined amount of counter-regulatory agent to a formula to calculate a corresponding quantity of carbohydrates. This formula may be generated based on the type of counter -regulatory agent and/or carbohydrates, physiological characteristics of the user, and/or clinical data.
  • the mapping may vary based on the glucose level control system 510.
  • the glucose level control system 510 may include a first mapping when the glucose level control system 510 (or medicament pump thereof) is a bi-hormonal pump configured to deliver insulin and counter-regulatory agent therapy to the subject, and may include a second mapping when the glucose level control system 510 is not configured to deliver the counter-regulatory agent therapy to the subject 512.
  • the glucose level control system 510 may store both mappings in the memory 540. For example, the glucose level control system 510 may use the first mapping when counter -regulatory agent is available and may use the second mapping when counter-regulatory agent is not available.
  • mappings may vary for a number of reasons including because a bi-hormonal glucose level control system 510 may more precisely control the occurrence of hypoglycemic events due to the availability of counter-regulatory agent, which may therefore alter the frequency and type of carbohydrates that a subject may consume.
  • the glucose level control system 510 outputs an indication of the dose of carbohydrate therapy.
  • Outputting the indication of the dose of carbohydrate therapy may include outputting an indication of the dose of carbohydrate therapy on a display for presentation to a user.
  • the indication of the dose of carbohydrate therapy may be transmitted to another computing system for display or aggregation with other therapy data associated with the subject 512, such as therapy data used by a clinician to help manager the subject’s 512 care.
  • the indication of the dose of carbohydrate therapy may be included in a report corresponding to care of the subject 512.
  • the operations of the process 700 are performed or repeated over a period of time.
  • the operations associated with the block 702-708 may be repeated one or more times over the period of time.
  • the determined doses of carbohydrate therapy may be aggregated for the period of time to determine a total carbohydrate therapy for the period of time.
  • the block 710 may include outputting an indication of the dose of carbohydrate therapy for each individual time that a dose of carbohydrate therapy is determined and/or the aggregated determined doses of carbohydrate therapy for the period of time.
  • the period of time may be any time period.
  • the period of time may be a day, week, month, year, since the subject 512 began using the glucose level control system 510, since a user obtained or ceased obtaining access to a counter - regulatory agent, or any other period of time.
  • the period of time is defined by the occurrences of hypoglycemic events or occurrences of the risk of hypoglycemia satisfying a threshold.
  • the period of time may be the time associated with 5, 10, 15, 100, or any other number of hypoglycemic events or occurrences of the risk of hypoglycemia satisfying a threshold.
  • the indication of total carbohydrate therapy may correspond to a reduction in carbohydrates consumed by the subject 512 because, for example, of the availability of counter-regulatory agent to the glucose level control system 510, and consequently, the subject 512.
  • the indication of total carbohydrate therapy may correspond to a reduction in carbohydrates achievable by an availability to the subject 512 of the counter -regulatory agent.
  • the indication of total carbohydrate therapy may correspond to an amount of counter-regulatory agent provided or that can be provided to the subject as a substitute for carbohydrates.
  • the particular carbohydrates consumed, or the amount of carbohydrates consumed by each subject or during each hypoglycemic event may vary.
  • a subject 512 may consume a particular candy bar when the subject’s 512 measured blood sugar level is too low or when the subject feels that the blood sugar level is likely low (e.g., begins to feel some hypoglycemic effects).
  • the subject may consume the whole candy bar or may consume a portion. Some of the candy bar may be lost to the subject (e.g., fall on the ground). In other cases, the subject may have different candy bars available, or other refined sugar sources, during different hypoglycemic events.
  • the amount of carbohydrates consumed or avoided due to the availability of counter-regulatory agent may vary for each hypoglycemic event. Accordingly, the indication of total carbohydrate therapy avoided, or that could be avoided if counter-regulatory agent were available, may indicate a range of carbohydrates that may potentially be replaced by the availability of counter -regulatory agent.
  • the indication of carbohydrate therapy or total carbohydrate therapy may include one or more of an indication of calories, an indication of carbohydrates, an indication of a measure of sugar, an indication of a quantity of food, or an indication of weight of the subject attributable to the carbohydrate therapy.
  • the indications may be associated with what is consumed due to a lack of counter-regulatory agent, or what is avoided based on the availability of counter-regulatory agent.
  • the indication of calories may be the number of calories not consumed because of the presence of the counter -regulatory agent.
  • the availability of therapy information relating to the carbohydrate therapy or avoided carbohydrate therapy can assist in patient care. For example, a subject can reduce refined sugar consumption that can have a number of health consequences. Further, a healthcare provider can better help a subject control his or her weight based on the carbohydrate information.
  • the indication of carbohydrate therapy may be presented to a user in any presentable form.
  • the indication of carbohydrate therapy may be presented as a table, a chart, a graph, a histogram, or other data presentation tool for indicating the reduction in carbohydrates over time that is achieved by the presence of counter -regulatory agent or that could be achieved by the use of counter-regulatory agent for the particular subject 512.
  • the indication of carbohydrate therapy data may vary for different users due to differences in physiological characteristics of the users, differences in the diabetes of each user, differences in lifestyle of each user, among other factors.
  • management of the subject’s 512 glucose level can be personalized.
  • Certain embodiments of the present disclosure relate to a method for translating an amount of online counter-regulatory dosing (e.g.
  • the method may include a mapping between the online counter-regulatory dosing, which was delivered to treat or prevent low glucose levels, and oral carbohydrates that are estimated to have otherwise been required to achieve a comparable safe control situation (had the counter-regulatory dosing not been delivered).
  • the method may include a mapping between the computed online counter-regulatory dosing and an estimated amount of oral carbohydrates that the subject will likely have been spared from needing to consume to treat or prevent low glucose levels had the counter-regulatory agent been available and its doses actually delivered.
  • embodiments disclosed herein include an autonomous glucose-control system where the counter-regulatory agent is glucagon.
  • the counter-regulatory agent is glucagon.
  • the method may include relating computed online glucagon dosing with consumed oral carbohydrates for the treatment or prevention of low glucose levels (“treatment carbs”) as observed in real use (e.g., during clinical studies) in the insulin-only configuration, and relating the relationship between the counter-regulatory agent and carbohydrates to a similar relationship between delivered online glucagon doses (or other counter-regulatory agent) and similarly consumed oral carbohydrates in the bi-hormonal (insulin-glucagon) configuration.
  • treatment carbs computed online glucagon dosing with consumed oral carbohydrates for the treatment or prevention of low glucose levels
  • treatment carbs relating the relationship between the counter-regulatory agent and carbohydrates to a similar relationship between delivered online glucagon doses (or other counter-regulatory agent) and similarly consumed oral carbohydrates in the bi-hormonal (insulin-glucagon) configuration.
  • Ci 0 the consumed treatment carbs in an insulin-only configuration
  • Gc the online computed (but not delivered) glucagon dosing
  • Ci 0 Ri 0 (x) * Gc
  • Ri 0 (x) may be a relating factor that can be a function of several dependencies that are included in vector x.
  • Such dependencies can include the specific insulin and/or glucagon being used (e.g., their clinical properties), and/or the pharmacokinetic settings assumed by the control system in relation to insulin and/or glucagon.
  • the dependencies can also include the user’s body mass and the glucose target used by the glucose -control system.
  • Rio(x) may be a constant, or Rio(x) o Rio, for a system exhibiting limited variation in the relationship between Ci 0 and G c (e.g., due to limited effect, or limited or no variation in the associated dependencies).
  • the quantities Ci 0 , G c , C bh , and G d can refer to daily amounts, as averaged over some period of use (e.g., a week).
  • the quantities Ci 0 , G c , C bh , and G d can refer to average daily amounts per body mass of the user, in which case dependency on body mass can be eliminated from x.
  • G c In cases where G c is computed, but no glucagon is actually delivered in an insulin- only system, G c has no effect on glucose insofar as treating or preventing low glucose levels, which in turn is generally expected to invoke further computed glucagon dosing (e.g., goes towards increasing the magnitude of G d for a given situation).
  • G d since G d is delivered in a bi-hormonal system, it is expected to have an effect in preventing or reducing the frequency, extent, or duration of low glucose levels, which in turn is expected to limit the overall magnitude of glucagon dosing (e.g., limits G d for a given situation).
  • real-use cases where the insulin-only system is used can be re-simulated while assuming a bi-hormonal system is available, where glucagon is assumed to be delivered. Since the control system may take delivered doses into account when issuing subsequent nearby glucagon doses, the simulated glucagon dosing may exhibit a reduction relative to the original G c of the insulin-only system. With the glucose profile kept unaltered in a simulation, the simulation may lack reflecting any resulting glucose excursions in response to the assumed delivered glucagon dosing. The simulation in turn may lack reflecting the full reduction in glucagon dosing down to G d that may have been observed if the glucose excursions had in fact benefited from glucagon being delivered.
  • the reduced glucagon dosing that is observed in the simulation, pseudo delivered glucagon G d may arguably be exaggerated in magnitude relative to what would have been the “real G d ”.
  • G c can be mapped to a corresponding amount Ci 0 in the insulin-only configuration
  • G d can be mapped to a corresponding amount C bh in the bi-hormonal configuration.
  • the simulation results therefore, can map the reduction “G c - to an estimate “Ci 0 - C bb ' of treatment carbs that the user would spare had they been using the bi-hormonal system.
  • the estimates may be conservative estimates.
  • mapping can be utilized when a bi-hormonal system is being used, where the observed dosing G d is mapped back to a pseudo computed glucagon G c and the resulting associated difference “C 10- C bh ” provides a (in some cases, conservative) estimate of the treatment carbs that the user had likely saved by virtue of being on the bi-hormonal system.
  • Certain embodiments include a system that comprises a controller for automatic control of a glucose level of a subject.
  • the controller may be operative to generate an insulin dose control signal based on time-varying glucose levels of the subject as represented by a glucose level signal over time.
  • the glucose level signal can be generated by a glucose sensor operative to continually sense a glucose level of the subject.
  • the insulin dose control signal may control the delivery of doses of insulin by a delivery device.
  • the controller can operate at a regular frequency to generate an insulin dose control signal to regulate the glucose levels in the subject.
  • the controller can employ a control algorithm that generates a glucagon dosing signal, which may be mapped to an associated amount of oral carbohydrates.
  • the oral carbohydrates may be associated with the prevention or treatment of low glucose levels. Further, the mapping between the glucagon dosing signal and the oral carbohydrates may be derived from analysis of clinical data.
  • the glucagon dosing signal may be computed, but not delivered in an insulin-only system configuration.
  • the glucagon dosing signal can be computed, and glucagon can be delivered in an insulin- glucagon system configuration.
  • the computed glucagon dosing in an insulin -only system configuration can be mapped to an amount of oral carbohydrates that is estimated to have been saved had glucagon dosing been delivered if an insulin-glucagon system configuration had instead been used.
  • the delivered glucagon dosing in an insulin-glucagon system configuration can be mapped to an amount of oral carbohydrates that is estimated to have been saved if an insulin-only system configuration had instead been used.
  • the mapping may be dependent on the clinical properties of the insulin and glucagon being used, and settings in the control system related to the action and effect of insulin and glucagon. Further, the mapping may be dependent on the subject’s body mass.
  • An ambulatory medicament device such as a glucose level control system (e.g., an insulin pump or a combined insulin and counter-regulatory agent (e.g., Glucagon) pump), can provide personalized therapy to a subject.
  • the ambulatory medicament device may provide medicament that is specific to a subject’s physiology, condition, activity, and the like.
  • some ambulatory medicament devices monitor a condition of the subject to determine when to provide therapy, what type of therapy to provide (e.g., insulin or counter- regulatory agent therapy), and/or how much therapy to provide.
  • the therapy provided by the ambulatory medicament device may be ongoing and, in some cases, lifesaving. Thus, it is important that ambulatory medicament device function uninterrupted.
  • the ambulatory medicament device may break, a subject may run out of or not have access to a necessary disposable (e.g., a replacement insulin cartridge, a site kit for changing the site of the ambulatory medicament device, a replacement battery, and the like), or the subject may forget to charge a battery of the ambulatory medicament device or not be in a location where a power source is available to charge the ambulatory medicament device.
  • a necessary disposable e.g., a replacement insulin cartridge, a site kit for changing the site of the ambulatory medicament device, a replacement battery, and the like
  • the subject may forget to charge a battery of the ambulatory medicament device or not be in a location where a power source is available to charge the ambulatory medicament device.
  • the ambulatory medicament device may not be available or may need replacing.
  • the ambulatory medicament device When the ambulatory medicament device is not available, or when a replacement (temporary or permanent) ambulatory medicament device is being used, it may be desirable to have an indication of the therapy settings from the ambulatory medicament device. For example, if a user (e.g., a subject, healthcare provider, parent, or guardian) is providing alternative therapy (e.g., injection therapy) while the ambulatory medicament device, it may be necessary to know the quantity of therapy to provide under particular circumstances or at particular times.
  • alternative therapy e.g., injection therapy
  • a healthcare provider may have access to therapy information that may have been previously determined, for example, via clinical testing.
  • This therapy information may include any type of information that can be used to determine therapy to provide to a subject at a particular time or under particular conditions.
  • the therapy information may indicate a setpoint insulin range for the subject, a quantity of insulin to provide to the user to adjust glucose levels, an amount of time for insulin to reach max concentration in the subject, or any other information that might impact the timing or amount of dosing of a medicament.
  • the therapy information available to the healthcare provider may be insufficient.
  • the subject may not be able to reach the healthcare provider to obtain the therapy information at a point in time when the information is needed.
  • the information may be outdated because, for example, the ambulatory medicament device may have refined the therapy over time. If the refinements have occurred recently, it is possible that the outdated values of the healthcare provider may be sufficient until a replacement ambulatory medicament device can repeat the refinement process of the original ambulatory medicament device.
  • the outdated therapy information may be insufficient because, for example, the refinements were significant or the subject may have had physiological changes (e.g., weight gain or weight loss, or metabolism changes) since the last time a clinical test was performed. Using outdated therapy information may be less effective and may cause discomfort or harm to a subject.
  • Certain embodiments of a system disclosed herein can generate backup therapy data.
  • a subject or user
  • the subject can maintain a level of therapy care that matches or more closely matches what was being provided by the ambulatory medicament device than clinical data, which may be outdated if available at all.
  • the system can include an automated glucose level control system (e.g., the glucose level control system 510) configured to generate a backup therapy protocol comprising insulin therapy instructions derived from autonomously determined doses of insulin.
  • the system may receive glucose level signals from a sensor operatively configured to determine glucose levels in a subject.
  • the sensor can include any type of sensor that can determine glucose levels.
  • the sensor may be a Continuous Glucose Monitoring (CGM) sensor.
  • CGM Continuous Glucose Monitoring
  • the system may autonomously determine and/or generate a dose control signal using a control algorithm.
  • the determination and/or generation of the dose control system may be performed without any user action or interaction with the glucose level control signal.
  • the lack of user action or interaction with the glucose level control system refers to conscious action and may exclude sensor measurements of physiological characteristics of the subject.
  • the control algorithm may autonomously determine doses of insulin to be infused into the subject for the purpose of controlling blood glucose of the subject based at least in part on the glucose level signal.
  • the control algorithm may include any type of control algorithm.
  • the control algorithm may be a bi -exponential pharmacokinetic (PK) model that models the accumulation of insulin doses in the blood plasma of the subject.
  • the automated blood glucose system may control delivery or administering of insulin or a counter- regulatory agent based on the bi-exponential PK model and one or more blood glucose measurements of the subject.
  • the bi -exponential PK model may model the absorption of subcutaneously administered insulin into blood and/or a rate of diminishing glucose in the blood.
  • the control algorithm may include a linear algorithm that models diminishing glucose or the accumulation of glucose in the subject based on a linear reduction rate. For example, the control algorithm may determine that a particular dose, D, of insulin is to be administered to the subject. The control algorithm may then estimate that 0.25*D of the insulin is absorbed into the blood plasma per hour over 4 hours. Similarly, the control algorithm may estimate that the insulin diminishes at a rate of 0.33 *D per hour over three hours upon the insulin reaching maximum concentration within the blood plasma. [0204] Regardless of the control algorithm used, the automated glucose level control system may administer insulin and, in some cases, a counter-regulatory agent one or more times over a particular time period.
  • the automated glucose level control system may provide a basal does of insulin on a periodic basis in an attempt to maintain a steady glucose level in the blood plasma of the subject.
  • the automated glucose level control system may supply mealtime boluses of insulin to account for an expected amount of glucose to be consumed as part of a meal.
  • the mealtime bolus may be an amount specified by a user or may be an amount of insulin administered in response to an indication of meal size by the subject. This indication of meal size may be subjective.
  • the size of the bolus of insulin for an identified meal size may be a fixed or constant value.
  • the size of the bolus of insulin for an identified meal size may vary over time as the automated glucose level control system learns or refines the amount of insulin to administer to a subject to keep the subject’s blood glucose within a target setpoint.
  • the automated glucose level control system may learn or refine the optimal insulin to administer based on a comparison of expected glucose level measurements to actual glucose level measurements when the subject (or other user) makes a subjective identification of meal size.
  • the automated glucose level control system may also supply correction doses of insulin to the subject based on the glucose level signal.
  • the correction doses of insulin may be supplied in response to a model predictive controller (MPC) determining or estimating that a user’s level of insulin is expected to fall below a threshold in some future period of time based on glucose level readings.
  • the MPC may execute a control algorithm that can regulate glucose concentration to a reference setpoint while simultaneously minimizing both the control signal aggressiveness and local insulin accumulation.
  • a mathematical formulation describing the subcutaneous accumulation of administered insulin may be derived based on nominal temporal values pertaining to the pharmacokinetics of insulin in the subject.
  • the mathematical formulation may be in terms of the insulin absorption rate, peak insulin absorption time, and/or overall time of action for the insulin (or another medicament). Examples of an MPC controller that may be used with embodiments of the present disclosure are described in U.S. Patent No. 7,806,854, issued on October 5, 2010, the disclosure of which is hereby incorporated by reference in its entirety herein for all purposes.
  • the automated glucose level control system may track insulin therapy administered to the subject over a tracking period.
  • the tracking period is not limited in length and may generally be any period of time, typically the tracking period is at least a minimum period of time sufficient for the automated glucose level control system to learn or refine the amount of medicament (e.g., insulin) to administer to the subject under particular conditions (e.g., when particular glucose levels are detected or when particular meal sizes are identified).
  • the automated glucose level control system may initially administer 6 units of insulin for lunch and 10 units of insulin for dinner. These initial values may be set be a healthcare provider and/or a subject based, for example, on clinical data for the subject.
  • the automated glucose level control system may determine that providing 7 units of insulin for lunch and 8 units of insulin for dinner maintains the subject’s glucose level closer to the median of the setpoint range than did the initial configuration.
  • each unit of insulin is 1/100 th of a milliliter of insulin.
  • the tracking period can be any length of time.
  • the tracking period could be 1 day, 3 days, 5 days, 7 days, anything in between, or more.
  • the tracking period is at least long enough to provide sufficient time to learn or refine initial settings of the automated glucose level control system for the subject.
  • the tracking period may be 1 or 2 days.
  • the tracking period may be from a particular time period until a current time period.
  • the tracking period may be from the start of therapy until a current point in time.
  • the tracking period may be a moving or shifting window.
  • the tracking period may be the least week, two weeks, month, or year.
  • the tracking period may differ based on the amount of time sufficient to determine or refine medicament control values for the subject.
  • the tracking period may a window of a particular length. This window may be a moving window.
  • the window may be the previous 7 days. As time passes, the window moves to continue to encompass the previous 7 days.
  • Tracking the insulin therapy may include storing the autonomously determined doses of insulin delivered to the subject. These autonomously determined doses of insulin may include one or more of basal insulin doses, mealtime insulin boluses, or correction insulin doses. Moreover, tracking the insulin therapy may including tracking the type of insulin used.
  • the type of insulin may include any type of insulin, such as fast-acting insulin (e.g., Lispro, Aspro, or Glulisin), regular or short-acting insulin (e.g., Humulin R, Novolin R, or Velosulin R), intermediate-acting insulin (e.g., Humulin N, Novolin N, ReliOn), long-acting insulin (e.g., detemir (Levemir), and glargine (Basaglar, Lantus)), or Ultra long -acting insulin (e.g., degludec (Tresiba), glargine u-300 (Toujeo)).
  • tracking the insulin therapy may include tracking counter-regulatory agent (e.g., Glucagon) therapy.
  • tracking the insulin therapy may include calculating average therapy provided over a period of time (e.g., over the tracking window). For example, the tracking the insulin therapy may include determining a moving average of the past 7 days of nominal basal doses during each dosing interval. Assuming basal therapy is provided every five minutes, the moving average may be calculated based on the previous 288 doses (e.g., over 1 day) or 2016 doses (e.g., over 7 days). This calculation can be used to obtain a basal rate profile for backup therapy. In some cases, the time period may be broken up into different time segments that may be associated with different rates of therapy.
  • basal therapy periods there may be 4 basal therapy periods (e.g., 10pm-4am, 4am-10am, 10am-4pm, and 4pm-10pm).
  • a separate moving average may be calculated for each of the basal therapy periods over a day, or over some other time period (e.g., 7 days).
  • the calculated averages may be used to calculate a backup basal rate that can be used to program an automated glucose level control system.
  • the basal rate profile may include aggregating the doses across the day to determine a dose of long-acting insulin that can be used for injection therapy.
  • a moving average of correction doses can be calculated to determine a correction bolus of insulin to supply via a pump or injection therapy.
  • the moving average of correction doses in combination with measurements of blood glucose of the subject over time may be used to determine a rate of change of blood glucose from a unit of insulin provided during correction therapy.
  • Mealtime boluses may also be calculated using a moving average. Further, a separate moving average may be calculated for each meal (e.g., breakfast, lunch, and dinner) dose over some period of time (e.g., 7 previous days of mealtimes). In some cases, each of the moving averages may be calculated using different windowing functions. For example, the moving average may be calculated using a Hann window or a Hamming window. In some cases, different levels of dosing may be determined for different meal sizes and different doses may be determined for different meals.
  • different meals may have different dosing despite similarity in size due, for example, to differences in the subject’s glucose levels when they wake up versus when they usually have lunch, or because differences in types of foods consumed at breakfast versus lunch. Further, in some cases, differences in metabolisms of different subjects may result in different mealtime boluses.
  • the insulin therapy may be stored in a therapy log, or any other type of data structure.
  • the insulin therapy may be stored in a memory of the automated blood glucose system, on a companion device, on a computing device of the subject or user (e.g., a laptop or desktop), in a cloud computing environment, or in any other storage system capable of receiving the insulin therapy information from the automated glucose level control system.
  • the automated blood glucose system, or a computing system with access to the therapy log or tracked insulin data may generate a backup insulin therapy protocol.
  • the backup insulin therapy protocol may include a backup injection therapy protocol or a backup pump therapy protocol.
  • the backup injection therapy protocol may include one or more amounts of insulin (or other medicament) to administer using injection therapy (e.g., manually provided shots) at one or more times to help maintain the subject’s condition within a normal or desired physiological range or condition.
  • the backup pump therapy protocol may include data and/or instructions for a replacement medicament pump of the same type or of a different type to supply therapy to the subject.
  • the replacement medicament pump may be a permanent replacement or a temporary replacement.
  • the backup pump therapy protocol may be the same as and/or include the same type of information as the backup injection therapy protocol. Alternatively, or in addition, the backup pump therapy protocol may include different values than the backup injection therapy protocol.
  • the backup pump therapy protocol may include an indication of basal therapy to provide periodically on relatively short increments (e.g., every 5 minutes, every half hour, every hour, etc.). Because an insulin pump may automatically administer insulin, it is possible to provide a steady or periodic drip of insulin. It may be impractical for a subject using injection therapy to administer insulin manually on similar short increments. Instead, a user might administer therapy on a less regular basis (e.g., once every roughly 4-5 hours or 6-8 hours, prior to mealtimes, after waking, and/or before sleeping, etc.). Accordingly, the backup therapy protocol for a pump and for injection may differ. Further, the type of insulin used or identified in the backup protocol may differ. For example, the backup protocol may call for use of long-acting insulin, such as, for example, insulin glargine, or intermediate - acting insulin, such as, for example human recombinant insulin.
  • long-acting insulin such as, for example, insulin glargine
  • intermediate - acting insulin such as, for example human re
  • the backup pump therapy protocol may be used to manually refine pump settings for a replacement glucose level control system to be used by the subject.
  • the replacement glucose level control system may automatically configure itself based on the backup therapy protocol. For example, a user may cause the backup therapy protocol to be provided to the replacement glucose level control system, which may use the information to self-calibrate.
  • therapy data may be useful in determining whether the subject is satisfied with therapy provided by the automated glucose level control system or whether the glucose level control system is configured in a way that best matches the subject’s lifestyle or therapy preferences (subjective or otherwise).
  • One way to determine whether the glucose level control system is providing desired therapy, or therapy at a desired rate, is to determine the frequency and/or magnitude of modifications made by the subject, or other user that may help manage a subject’s therapy, to therapy provided by the automated glucose level control system.
  • the automated glucose level control system disclosed herein can track user modifications to a control parameter over a tracking period.
  • the tracking period may include any time period described herein for tracking therapy to generate a backup protocol.
  • the control parameter may include any type of control parameter that may affect the administering of therapy.
  • the control parameter may relate to a quantity of therapy, a timing of delivered therapy, a rate that therapy is delivered, or a trigger of when or whether to deliver therapy, among other control parameters.
  • control parameters may directly affect the delivery of therapy (e.g., specify a time to deliver the medicament or a quantity of medicament to deliver) or may indirectly affect therapy (e.g., adjust a setpoint range to maintain blood glucose or a rate of insulin accumulation in the subject, which may be used to modify a control algorithm for administering therapy).
  • therapy e.g., adjust a setpoint range to maintain blood glucose or a rate of insulin accumulation in the subject, which may be used to modify a control algorithm for administering therapy.
  • the user modifications may include any change to the control parameter or settings of the automated glucose level control system.
  • the automated glucose level control system may track each instance and/or the rate or percentage of times a user reduces or increases a control parameter (e.g., an amount of administered insulin).
  • tracking changes to the control parameter may including tracking how often a user pauses therapy or temporarily adjusted a target blood glucose range, or other control parameter.
  • tracking changes to the control parameter may include tracking when a user makes changes to the control parameter.
  • the user may generally modify the control parameter at night, but leave the daytime parameter unchanged, or vice versa.
  • the automated glucose level control system may track a subject’s weight over time. The weight may be provided by a user and may affect the glucose level control (e.g., an amount of insulin administered may be related to a subject’s weight).
  • the automated glucose level control system may generate a report that tracks user modifications to the control parameter.
  • the report may comprise a measure of the frequency of increases and decreases from the stored control parameter value. Further, the report may include an indicator of a percentage of times a user modified a control parameter higher or lower than the stored control parameter value of the automated glucose level control system over the tracking period. In some cases, the report indicates the number of times that the infusion of insulin is paused over the tracking period, or the speed (e.g., aggressiveness) that insulin is delivered to the subject.
  • a clinician or other healthcare provider can determine whether modifications should be made to a control parameter to better manage a subject’s therapy. For example, if it is determined that a subject is raising a blood glucose target level 4-5 times a week during an evening time or nighttime, the clinician may determine that the target setpoint for the evening should be adjusted to reduce the number of occurrences that a user manually adjusts therapy, or control parameter settings for therapy, provided by the automated glucose level control system. In some cases, the subject may be adjusted therapy based on subjective reasons. In some such cases, the therapy report may enable the clinician or healthcare provider to train the subject on controlling his or her disease. In other cases, the clinician may determine that the subject has a different tolerance for blood glucose than initially determined or than an average subject and may adjust one or more control parameters of the automated glucose level control system accordingly.
  • the automated glucose level control system may automatically adjust one or more control parameters over time based on the report. For example, if the automated glucose level control system determines that over a course of a month the subject adjusted lower a daytime target glucose range 20 out of 30 days, the automated glucose level control system may modify a control parameter to have a lower setpoint range. In some cases, the automated glucose level control system may communicate the change to a user, such as the subject, a parent or guardian, or a healthcare provider.
  • FIG. 8 presents a flowchart of an example backup therapy protocol generation process 800 in accordance with certain embodiments.
  • the process 800 may be performed by any system that can track medicament therapy (e.g., insulin therapy) provided to a subject over time and generate a backup therapy protocol that may be used if a glucose level control system 510 becomes unavailable.
  • the process 800 may be performed by one or more elements of the glucose level control system 510.
  • at least certain operations of the process 800 may be performed by a separate computing system that receives indications of medicament therapy provided to the subject 512 from the glucose level control system 510.
  • one or more different systems may perform one or more operations of the process 800, to simplify discussions and not to limit the present disclosure, the process 800 is described with respect to particular systems.
  • the process 800 begins at block 802 where the glucose level control system 510 receives a glucose level of a subject 512.
  • Receiving the glucose level may include receiving and/or determining a glucose level signal corresponding to a glucose level of the subject.
  • the glucose level signal may be received from the glucose sensor 516 (e.g., a CGM sensor).
  • the glucose level may be received from a user that provides the glucose level to the glucose level control system 510 via a user interface, such as a user interface generated by the processor 530 that may be output on a touchscreen by the touchscreen controller 538.
  • the glucose level received from the user may be a glucose level measured using an alternative sensor or measurement mechanism (e.g., diabetes measurement strips) that may be used in place of the glucose sensor 516.
  • the glucose level control system 510 generates an insulin dose control signal based at least in part on the glucose level signal.
  • the insulin dose control signal may be a medicament control signal configured to control a medicament pump to administer medicament (e.g., insulin, counter-regulatory agent, or other medicament) to a subject 512.
  • medicament e.g., insulin, counter-regulatory agent, or other medicament
  • the dose control signal may be generated using a control algorithm configured to autonomously determine doses of insulin to be administered to or infused into the subject for the purpose of controlling blood glucose of the subject based at least in part on the glucose level or glucose level signal determined at the block 802.
  • the glucose level control system 510 tracks insulin therapy administered to the subject 512 over a tracking period.
  • the tracking period is typically at least one day and may be longer.
  • the tracking period may be 1 day, 2 days, a week, a month, several months, a year, any length of time between the foregoing examples, or even longer.
  • the tracking period may be continuous from a point in time when tracking begins.
  • the tracking period may encompass the entire usage lifetime of the glucose level control system 510 by the subject 512.
  • the process 800 may be repeated periodically, upon request, or upon a triggering event using a new tracking period, of equal or different length.
  • the triggering event may include any event that may render a prior generated backup therapy protocol potentially out-of-date.
  • the triggering event may include a change in medicament type (e.g., different insulin or counter-regulatory agent formulations), a change in physiological characteristics of the subject 512 (e.g., a change in weight, or sensitivity to different glucose levels or medicament), or a change in average activity level of the subject 512.
  • the tracking period is typically at least one day enabling the glucose level control system 510 to determine a backup protocol based on data from a full cycle (e.g., waking and sleeping hours) of glucose level control system 510 use
  • the tracking period may at least initially be less than a day.
  • an initial backup therapy protocol may be generated after a half-day’s activity. This initial backup therapy protocol may be updated as more data becomes available throughout the day’s (and, in some cases, subsequent day’s) use of the glucose level control system 510.
  • the tracking period may be defined by or based on a particular number of insulin administering events.
  • the tracking period may be defined by at least ten instances of generating an insulin dose based on a glucose level signal.
  • the tracking period may be defined by a minimum number of meal events, correction dose events, and/or basal dose events.
  • the tracking period may require 3 meals, or 3 meals of each meal type to occur, 2 correction doses, and/or 100 basal doses. It should be understood that the aforementioned number of doses is just an example, and the tracking period may include more or fewer dose amounts.
  • the tracking period may be defined or specified as a combination of time and occurrences of a particular number of doses of insulin.
  • the tracking period may be variable. For example, if the glucose level control system 510 determines that the insulin dose therapy is inconsistent or erratic over the tracking period (e.g., due to inconsistent exercise or eating habits), the tracking period may be extended.
  • Tracking the insulin therapy may include storing the insulin dose control signal generated based at least in part on the glucose level signal at the block 804.
  • tracking the insulin therapy may include storing an indication of a quantity of insulin (or other medicament) corresponding to the insulin (or another medicament) dose control signal.
  • the insulin dose control signal and/or the indication of the quantity of insulin may correspond to a dose of insulin delivered to the subject 512 as a basal insulin dose, a correction bolus of insulin, and/or as a mealtime bolus of insulin.
  • Storing the insulin dose control signal and/or the indication of the quantity of insulin may include storing the insulin dose control signal and/or the indication of the quantity of insulin in a therapy log or any other type of data structure in the memory 540 of the glucose level control system 510.
  • the glucose level control system 510 may store the insulin dose control signal and/or the indication of the quantity of insulin at a remote data store.
  • This remote data store may be a local computing system with which the glucose level control system 510 may communicate (e.g., a laptop, desktop, smartphone, or other computing device of the subject 512 or a user).
  • the glucose level control system 510 may provide the insulin dose control signal data or the indication of the quantity of insulin to the local computing system via Bluetooth® or other near field communication services, or via a local network.
  • the remote data store may be a remote computing system that the glucose level control system 510 may communicate with over a wide area network, such as a wireless area network, a cellular network using IoT based communication technology, cellular communication technology, or any other communication network.
  • the wide area network may include the Internet.
  • the glucose level control system 510 may include a wireless radio that enables it to communicate with the local or remote computing system.
  • the remote computing system may be a computing system of a data center or a cloud computing environment.
  • the glucose level control system 510 may establish a communication channel with the computing system. This communication channel may be an encrypted channel. Further the communication channel may be a direct end-to-end connection between the glucose level control system 510 and the computing system. Once the communication channel is established, the glucose level control system 510 may transmit the insulin dose control signal data or the indication of the quantity of insulin to the computing system.
  • tracking the insulin therapy may include storing insulin does control signals and/or corresponding indications of quantities of insulin for a plurality of autonomously determined doses of insulin infused into the subject 512 throughout the tracking period.
  • counter-regulatory agent therapy includes administering a counter- regulatory agent (e.g., glucagon) when there is a risk or occurrence of hypoglycemia. Usually, the counter-regulatory agent is not supplied on periodic or daily basis.
  • counter-regulatory agent is administered to the subject 512.
  • it may help a healthcare worker or user guide or adjust care for the subject 512.
  • tracking counter-regulatory agent use may help determine a minimum quantity of counter-regulatory agent that should be accessible to the subject 512, either in a bi-hormonal pump or for use in injection therapy.
  • the block 806 may include tracking the counter-regulatory agent administered during the tracking period. Tracking the counter-regulatory agent therapy may include storing an indication of autonomously determined doses of counter-regulatory agent delivered to the subject 512 responsive to the glucose level signal obtained at the block 802.
  • the glucose level control system 510 generates a backup therapy protocol based at least in part on the tracked insulin therapy.
  • the backup therapy protocol may be determined based on an average quantity or rate of insulin administered to the user over the tracking period, over different portions (e.g., breakfast, lunch, and dinner, or waking and sleeping hours, etc.) of the tracking period, or in response to particular events (e.g., when eating, when glucose level exceeds a threshold level, etc.).
  • the backup therapy protocol may include a backup injection protocol and/or a backup pump therapy protocol.
  • the backup injection protocol may provide a user (e.g., the subject 512, a parent or guardian, or other caretaker for the subject 512) with quantities of insulin that may be administered to the subject 512 via injection.
  • the backup injection therapy may indicate times that the insulin may be administered.
  • the backup injection therapy may indicate quantities of insulin to be administered at particular mealtimes.
  • the backup injection therapy may indicate an effect that a unit of insulin may have on the subj ect 512 enabling a user to calculate how much insulin to administer to the subject 512 when a blood glucose reading indicates that the glucose level of the subject 512 is too high (e.g., above a desired setpoint range).
  • the backup pump therapy protocol may provide a user (e.g., the subject 512, a parent or guardian, or other caretaker for the subject 512) with quantities of insulin that may be administered to the subject 512 via a medicament pump.
  • a user may configure the medicament pump to administer the quantities of insulin identified.
  • the backup pump therapy protocol may be used to configure the medicament pump when access to a CGM sensor is unavailable (e.g., the subject 512 does not possess a CGM sensor, or the medicament pump or CGM sensor has a fault, etc.). Further, the backup pump therapy protocol may be useful for providing an initial configuration to a replacement glucose level control system.
  • the backup injection therapy protocol and the backup pump therapy protocol may be the same. However, often at least the recommended basal therapy settings may differ. It is generally not practicable for insulin to be administered to a subject 512 more than a few times a day via injection therapy.
  • the backup injection therapy protocol may identify long-acting insulin units or doses that may be administered on a limited basis (e.g., once or twice a day).
  • the medicament pump may more easily administer insulin on a more than limited basis (e.g., every hour, every half hour, every 5 minutes, etc.).
  • the backup pump therapy protocol may identify a basal rate of insulin that may be administered once every time unit (e.g., once per hour or once per 15 minutes, or once per five minutes), or continuously at a particular rate (e.g., 0.5 or 0.6 units) per time unit (e.g., per hour).
  • the backup pump therapy protocol may identity different rates for different portions of a day (e.g., one rate each half of the day, one rate each quarter of the day, or one rate during typical waking hours and one rate during typical sleeping hours for the subject, etc.).
  • an initial backup therapy protocol may be generated at the block 808.
  • the initial backup therapy protocol may be updated over time as additional insulin therapy data is obtained.
  • Generating the backup therapy protocol may include determining a number of long- acting insulin units based at least in part on an average total basal insulin provided to the subject 512 per day over the tracking period.
  • the averaged total basal insulin provided per day may be included in a backup injection therapy protocol as a single dose of long-acting insulin that is configured to help maintain the basal insulin level of the subject 512 throughout the day.
  • the averaged total basal insulin provided per day may be included in a backup injection therapy protocol as multiple doses of insulin (e.g., 2 or 3 doses throughout the day).
  • the basal insulin may be included in the backup therapy protocol, such as in a backup pump therapy protocol, as a dosage rate that may be supplied to a pump to provide a rate of basal insulin throughout the day.
  • each day of the tracking period may be divided into a plurality of sub -periods.
  • each day of the tracking period may be divided into two, three, four, or more time periods, or equal or different length.
  • generating the backup therapy protocol may include determining an hourly basal rate for each sub-period of the plurality of sub-periods. This hourly basal rate may be determined by averaging the corresponding sub -periods for each day of the tracking period.
  • the basal rate supplied during the first sub-period throughout the tracking period may be averaged and the basal rate supplied during the second sub-period throughout the tracking period may be averaged to determine two basal rates for inclusion in the backup therapy protocol.
  • the basal rate may be determined on an hourly rate or based on any other time period.
  • the basal rate may be determined based on an amount of time that a particular quantity (e.g., one unit) of insulin is recommended to be administered to the subject 512 as part of the backup therapy protocol.
  • the backup therapy protocol may indicate the basal rate to be one unit every 1.125 hours.
  • the backup therapy protocol may indicate a basal rate of 0.89 units per hour.
  • generating the backup therapy protocol may include determining an average correction bolus provided to the subject per day over the tracking period.
  • the average correction bolus may be determined by adding the total amount of correction doses administered each data and dividing by the number of days in the tracking period.
  • the average correction bolus may be included in the backup therapy protocol as guidance for the user.
  • the correction bolus is supplied in response to a determination that a subject’s glucose level is spiking or exceeding a threshold, and not necessarily as a daily dose of insulin.
  • the average correction bolus may be included as part of the backup therapy protocol to facilitate the user understanding an amount of insulin that is likely to be required during an average day, which may be useful for the user (e.g., the subject) to determine how much insulin to have accessible to use, for example, in injection therapy.
  • one or more days, or time periods, of the tracking period may be omitted when determining the average correction bolus because, for example, the one or more days or time periods may be determined to be outliers. The outliers may be omitted to provide a more accurate understanding of average insulin needs or consumption.
  • the glucose level control system 510 may determine an average change in blood glucose at least partially attributable to a unit of insulin provided as a correction bolus to the subject during the tracking period. In some cases, the glucose level control system 510 may correlate each correction bolus applied during the tracking period to a change in the glucose level of the subject 512.
  • Generating the backup therapy protocol may include determining, for each mealtime of a plurality of mealtimes per day, an average mealtime bolus of insulin provided to the subject over the tracking period.
  • the average mealtime bolus may be determined for particular meals (e.g., breakfast, lunch, and dinner), while other periods of food intake (e.g., snacks or teatime) may be omitted or ignored.
  • the average mealtime boluses may be associated with particular meal sizes as identified by a user.
  • the glucose level control system 510 may determine an average mealtime bolus for a small and a large meal, or for a small, a medium, and a large meal.
  • the average mealtime bolus may be determined by averaging an amount of insulin the glucose level control system 510 determines should be administered to the subject 512 using a control algorithm of the glucose level control system 510 for each mealtime and identified meal size.
  • the backup therapy protocol may include data relating to the administering of counter-regulatory agent.
  • the backup therapy protocol may include an indication of total counter-regulatory agent and/or daily counter-regulatory agent provided to the subject over the tracking period.
  • the glucose level control system 510 outputs the backup therapy protocol.
  • Outputting the backup therapy protocol may include displaying the backup therapy protocol on a display enabling a user to implement the backup therapy protocol.
  • outputting the backup therapy protocol may include transmitting the backup therapy protocol to a computing device of a user for display and/or storage.
  • the backup therapy protocol may be stored at the glucose level control system 510 and may be accessed in response to a user interaction with a user interface of the glucose level control system 510.
  • the process 800 can be combined at least in part with the process 900 described herein.
  • the backup therapy protocol may further include a record of user modifications to one or more control parameters used by the control algorithm of the glucose level control system 510 to autonomously determine doses of insulin to be infused into or administered to the subject.
  • This record of user modifications may include an identity of instances of user modification to the control parameter and/or a percentage of times a user modified the control parameter during each day of the tracking period and/or during the entire tracking period.
  • FIG. 9 presents a flowchart of an example control parameter modification tracking process 900 in accordance with certain embodiments.
  • the process 900 may be performed by any system that can track user interactivity with glucose level control system 510, and more specifically, occurrences of a user modifying a control parameter used by the glucose level control system 510 to help control medicament delivery to the subject 512.
  • the process 900 may be performed by one or more elements of the glucose level control system 510.
  • At least certain operations of the process 900 may be performed by a separate computing system that receives indications of changes to control parameter settings of the glucose level control system 510 from the glucose level control system 510 and/or from user interaction with a user interface at the separate computing system prior to transmitting the modification to the glucose level control system 510.
  • a separate computing system that receives indications of changes to control parameter settings of the glucose level control system 510 from the glucose level control system 510 and/or from user interaction with a user interface at the separate computing system prior to transmitting the modification to the glucose level control system 510.
  • the process 900 begins at block 902 where the glucose level control system 510 receives a glucose level of a subject 512.
  • the block 902 can include one or more of the embodiments previously described with respect to the block 802.
  • the glucose level control system 510 generates an insulin dose control signal based at least in part on the glucose level signal and a control parameter.
  • the insulin dose control signal may be generated based on a control algorithm that enables the glucose level control system 510 to autonomously determine doses of insulin to be infused into or administered to the subject to control the glucose level of the subject.
  • the control algorithm may determine the doses of insulin based at least in part on the control parameter.
  • the control parameter may include any parameter that can affect the operation or output of the control algorithm, or the operation of the glucose level control system 510, and that is modifiable by a user (e.g., the subject 512 or a user that is at least partially responsible for care of the subject 512 (e.g., a parent or guardian)).
  • the control parameter may be, or may correspond to, a target setpoint for the glucose level of the subject 512.
  • the control parameter may correspond to whether the glucose level control system 510 is to generate the insulin dose control signal for at least a period of time.
  • the control parameter may relate to whether at least some operation of the glucose level control system 510 is paused or active.
  • the block 904 can include one or more of the embodiments previously described with respect to the block 804.
  • the glucose level control system 510 tracks one or more user modifications to the control parameter over a tracking period.
  • the tracking period may be one day, less than a day, or it may be longer than one day (e.g., 2 days, 3 days, a week, a month, etc.). Further, the tracking period may include one or more periods of time as previously described with respect to the process 800.
  • the user may be the subject 512 or any other user (e.g., a parent or guardian, or a healthcare provider) that may be permitted to modify a control parameter of the glucose level control system 510.
  • the user may modify the control parameter using a user interface that may be generated and/or output by the glucose level control system 510.
  • the user interface may be generated and/or output by a computing system that can communicate with and/or modify the control parameter at the glucose level control system 510.
  • the computing system may be a smartphone, a smartwatch, a laptop, or desktop computer, or any other type of computing device that may be used to configure the glucose level control system 510.
  • the user interface may be output on a touchscreen with which the user may interface to modify the control parameter.
  • the user may interact with a control parameter selection element or other user interface element to select and/or modify the control parameter.
  • the user may provide the control parameter with any value supported by the glucose level control system 510.
  • the user may be limited to selecting particular values for the control parameter, which may be less than the supported capability of the glucose level control system 510 or less than what other users are permitted to select. For example, a clinician may be granted a greater modification range than a parent for modifying the control parameter.
  • Tracking the one or more user modifications may include storing in the one or more user modifications in a therapy log, database, or other data structure. Further, tracking the one or more user modifications may include tracking or storing whether each of the user modifications comprises an increase or a decrease in the control parameter. The determination of whether the control parameter has been increased or decreased may be determined based on whether a value for the control parameter has been increased or decreased relative to a reference value. The reference value may include a current value of the control parameter, a default value, a clinical value supplied to the glucose level control system 510, and/or a value determined by the glucose level control system 510. Further, tracking the one or more user modifications may include storing a time and/or one or more conditions under which the control parameter is modified.
  • the glucose level control system 510 may store a time of day, an activity level of the subject 512 as determined from one or more physiological sensors and/or as identified by a user, a meal being consumed or not consumed, and the like.
  • tracking the insulin therapy may include storing an indication of the autonomously determined doses of insulin delivered or administered to the subject 512.
  • the tracking period may be divided into a plurality of sub -periods. The sub-periods may correspond to different portions of a day within the tracking period. For example, each day of the tracking period may be divided into two equal halves corresponding roughly to day and night, or into 3 or 4 different periods corresponding to a particular number of hours in the day.
  • the sub-periods may be of equal or unequal length. Tracking the one or more user modifications may include tracking the occurrence of modifications to the control parameter within the sub -periods of the tracking period. Further, the occurrence of modifications within a sub -period of a day within the tracking period may be combined with the occurrence of modifications within a corresponding sub -period of another day within the tracking period. In other words, each occurrence of a modification of a control parameter in a sub-period defined from 9:00-21:00 may be aggregated across days of the tracking period. [0252] In some cases, a different reference value may be determined for the control parameter for each sub-period. In some such cases, tracking the one or more user modifications may include tracking modifications to the control parameter value with respect to the reference value for the sub -period.
  • the glucose level control system 510 generates a report of user modifications to the control parameter.
  • the repot may be generated by another computing system, such as a cloud computing system or a computing system of a healthcare provider based on data (e.g., occurrences of user modification of the control parameter value) received from the glucose level control system 510.
  • the report may include a measure of frequency of increases and decreases from the stored control parameter value. Further, the report may indicate a number of times that operation of one or more features of the glucose level control system 510 has been paused or suspended, or a percentage of the tracking period that operation of one or more features of the glucose level control system 510 has been paused or suspended. Moreover, the report may indicate a magnitude of the modification to each control parameter for each occurrence, in total, and/or on average. In some cases, the report may indicate a percentage of user modifications that are higher or lower than the reference value over the tracking period.
  • the report may include a measure of frequency of increases and decreases from a reference value for the control parameter for each sub -period of the tracking period.
  • the report may include an identity of user activity that occurred when, or within a threshold time period, of a user modification to a value of the control parameter. For example, the report may identify whether a user was exercising (e.g., swimming, running, dancing, etc.) when a user modification to the control parameter value was made.
  • the block 908 may include storing the generated report at the glucose level control system 510 (e.g., in the memory 540) and/or at a storage of another computing device.
  • the computing device may be a computing device of the subject 512 (or parent or guardian). Further, the computing device can be a computing device of a healthcare provider. In some cases, the computing device may be a computing device of a cloud computing service.
  • the report may be obtained from the glucose level control system 510 by a wired connection (e.g., a USB cable). Alternatively, or in addition, the report may be obtained via a wireless connection to the glucose level control system 510.
  • the glucose level control system 510 may establish an encrypted connection to a computing system of a healthcare provider, which may receive the report from the glucose level control system 510.
  • the glucose level control system 510 may establish an encrypted communication channel with a cloud computing provider, which can receive the report from the glucose level control system 510. This report may then be accessed by any authorized users.
  • a healthcare provider can use the report to help manage care of the subject 512. For example, if the healthcare provider determines that a user is modifying the control parameter more than a threshold number of times or during particular time periods, the healthcare provider may use this information to modify the care being provided to the subject 512 and/or to educate the subject 512 on optimal care. For example, the rate of therapy may need to be modified or the amount of insulin may be too low for the subject’s comfort. For example, in some cases, a subject 512 may have a different tolerance to a glucose level than the average user leading the user to modify a setpoint range.
  • the process 900 may be combined with the process 800.
  • a report may be generated that includes both backup therapy protocols and a record of the number of times a user may a modification to one or more control parameters of the glucose level control system 510.
  • the processes 800 and 900 may be triggered and/or performed independently.
  • FIGS. 10-12 illustrate one non-limiting example of a backup therapy report, or a set of reports, that may be generated using one or more of the embodiments disclosed herein.
  • the reports of FIGS. 10-12 may be portions of a single report generated by the glucose level control system 510 or may be separate reports that are concurrently generated or that are generated based on different data and/or over different tracking periods.
  • the report may be generated by the automated glucose level control system 510, or by another computing system that may receive therapy data from the automated glucose level control system.
  • FIGS. 10-12 represent just one non-limiting example of a report or set of reports that may be generated. It is possible for other reports to be generated that include more or less data.
  • the backup injection therapy protocol and the backup pump therapy protocol illustrated in FIG. 10 may be separated into two separate reports that may be separately generated and/or accessed.
  • FIG. 10 illustrates an example backup therapy protocol report 1000 in accordance with certain embodiments.
  • the amount of insulin recommended under different ties and/or conditions may be displayed in units.
  • the report 1000 may identify the quantity of insulin included in a unit and/or the type of insulin.
  • the report 1000 may be an interactive report that enables a user to modify a type of insulin or a unit size of insulin.
  • the table 1002 may update the recommended number of units of insulin to administer under particular times or conditions based on the type of insulin and or unit size of insulin selected.
  • the report 1000 may identify the length of the tracking period 1006 used to determine the backup therapy protocol. Further, the report 1000 may identify the time or date range 1008 during which the tracking period 1006 occurred.
  • knowing the tracking period 1006 may help determine an amount of trust to place in the recommendations included in the backup therapy protocols. The longer the tracking period, the more likely that the recommendations are accurate. A shorter tracking period is more susceptible to less accurate recommendations because, for example, the tracking period may encompass more days that are outliers for the subject’s typical condition or activity level. For example, a tracking period of one day that occurs on a day when a subject consumed larger than normal meals or exercised significantly more than normal may result in backup therapy recommendations that do not match the subject’s typical lifestyle.
  • knowing when the tracking period occurred may be useful to determine how current the recommendations are and whether they are a reliable indicator of an amount of insulin a subject should administer. For example, if the time or date range 1008 of the tracking period 1006 is a year old, and the subject has gained or lost significant weight over the year, the backup therapy protocol may no longer be a reliable indication of recommended injection therapy. In such cases, a user may adjust the recommendation and/or trigger a new occurrence of the process 800.
  • the table 1002 illustrates an example backup injection therapy protocol, which may indicate various insulin doses that may be administered to the subject 512 at various times or under various conditions using injection therapy.
  • the table 1002 identifies an amount of insulin the subject 512 may inject when consuming a usual -sized meal for breakfast, lunch, or dinner.
  • the usual-sized meal may refer to the size of a meal that the particular subject 512 usually consumes or has been advised to consume by a healthcare provider.
  • the units of insulin specified may refer to an amount of insulin that the automated glucose level control system 510 provides the subject 512 on average when the user consumes the identified usual size meal.
  • the table 1002 may further include recommended insulin doses for different size meals.
  • each breakfast may illustrate three different values (e.g., 5 units, 6 units, and 8 units) corresponding to light or smaller than usual breakfast, usual size breakfast, and heavy or larger than usual size breakfast.
  • the amount of insulin delivered may vary over time and/or based on the condition of the patient at a particular time.
  • the recommendations in the backup therapy protocols are suggested for temporary use for a particular quantity of time (e.g., up to 72 hours in the illustrated example).
  • the quantity of time for which the recommendations are valid may vary based on the subject 512, the amount of historical data collected (e.g., the size of the tracking period), the amount of daily variation in the subject’s glucose level, or any number of other factors that may affect the amount of time that the backup therapy protocol can be safely followed.
  • the backup injection therapy protocol may further identify an amount of long-lasting insulin a subject 512 is recommended to administer each day (or at certain times throughout the day). This long-lasting insulin may be used in place of the basal insulin that the glucose level control system 510 may provide on a periodic basis.
  • the table 1002 identifies the reduction in glucose level attributable to one unit of insulin. For example, as illustrated in the table 1002, the automated glucose level control system 510 has determined that one unit of insulin (e.g., 1/100th of a milliliter of insulin) may reduce a subject’s 512 glucose level by 9 mg/dL.
  • a user implementing injection therapy may measure a subject’s 512 glucose level, determine a difference between the measured glucose level and a desired setpoint or threshold glucose level, and divide the difference by 9 to determine a number of units of insulin to inject in response to a determination that a correction dose is warranted (e.g., that blood glucose is outside of a desired setpoint range).
  • the table 1004 of the report 1000 provides an example of a backup pump therapy protocol.
  • the backup pump therapy protocol may have the same therapy information as the backup injection therapy protocol for mealtimes and for the correction factor.
  • the long-acting insulin units of the injection therapy may be replaced with a basal rate indicating a rate at which the backup or replacement pump should administer insulin to the subject.
  • the basal rate may vary over time. In the illustrated example, a basal rate is supplied for four different time periods constituting a 24-hour day.
  • the basal rate may be divided into a fewer (e.g., 2 twelve-hour blocks) or greater (e.g., every four hours) number of periods, with each time period potentially having a different basal rate as determined based on the historical therapy data provided by an automated glucose level control system.
  • the report 1000 may include additional data that may be tracked over the tracking period. This additional data may include any data that may facilitate care of the subject 512 and/or maintenance of the automated glucose level control system 510.
  • additional data may be tracked and included in a report using, for example, the process 800 or 900 are illustrated in chart 1010 of the report 1000.
  • the report may include the average glucose level of the subject 512 over the tracking period and/or the corresponding estimated AIC percentage.
  • the report 1000 may indicate the amount or percentage of time that the subject’s glucose level is within a desired setpoint range and/or is above the desired setpoint range.
  • the report 1000 may indicate the amount or percentage of time that the subject’s glucose level is below a threshold glucose level.
  • the report 1000 may indicate the average number of meal announcements per day. As illustrated in the chart 1010, the subject 512 from which the example report 1000 was generated made an average of 4.2 meal announcements indicating that on average, the subject consumed more than 3 meals a day. In some cases, the report may further indicate the types of meals announced (e.g., two breakfasts, one lunch, and one dinner). The second breakfast may be a large snack that is roughly equivalent in size to a small breakfast for the subject. Thus, the subject may have made an additional breakfast meal announcement. In some cases, the automated glucose level control system 510 may support a separate snack or other meal announcement option.
  • the report 1000 may further include the total amount of insulin administered to the subject per day, and/or the total amount of counter-regulatory agent (e.g., glucagon) administered to the subject per day.
  • the report 1000 may indicate the amount of percentage of time that the automated glucose level control system 510 is able to connect or communicate with the CGM sensor over the tracking period, which may correspond to the amount of time that the automated glucose level control system 510 functions in an online mode during the tracking period.
  • FIG. 11 illustrates an example control parameter modification report 1100 in accordance with certain embodiments.
  • the report 1100 may be a separate report generated using, for example, the process 900. Or the report 1100 may be included as a second within the report 1000.
  • the report 1100 may generally provide an indication of the number or percentage of times that a user modified one or more control parameters of the automated glucose level control system 510 during a tracking period. Further, as with the report 1000, the report 1100 may identify the time or date range 1008 during which the tracking period 1006 occurred. In some cases, a user may interact with the report 1100 to determine the number of percentage of times that the user modified one or more control parameters during a subset of the tracking period. Similarly, the user may filter or narrow the date range to view other data described herein for a subset (e.g., a selected data range) of the tracking period.
  • a subset e.g., a selected data range
  • the report 1100 may include a graph 1102 that illustrates the subject’s glucose level with respect to the desired target setpoint range over the course of a day during the tracking period. This day can be an average of the values obtained for each day over the tracking period, or it can illustrate a particular selected day.
  • the report 1100 may include a table 1104 that indicates the percentage of times that a user modified the blood glucose target during specific time periods.
  • the table 1104 of the non-limiting example report 1100 indicates two time-periods, daytime and nighttime. However, it should be understood that the table 1104 may indicate fewer or more time periods. Further, the time periods may indicate specific times (e.g., from 9:00 to 21:00 and from 21 :00 to 9:00) for the time periods.
  • the table 1104 may indicate the percentage of times that a user increased or decreased glucose target setpoints.
  • the report may indicate the percentage of times that the user did not modify, or left as usual, the glucose target setpoint.
  • This target setpoint indicated in the table 1104 may refer to a single target value (e.g., 110 mg/dL, 125 mg/dL, 130 mg/dL, etc.), or may refer to a target setpoint range (e.g., 70-180 mg/dL).
  • the report 1100 may indicate the number of times that a user set a temporary glucose target during the tracking period (the temporary target count 1106) or a selected data range.
  • the report may also indicate a number of times that the user paused therapy during the tracking period (e.g., the paused insulin therapy count 1108) and/or the selected date range.
  • the blood glucose of a subject may be affected by a subject’s weight. Accordingly, the subject may provide updates of weight to the automated glucose level control system.
  • the report may indicate a change in weight and when the weight parameter was modified (e.g., body weight data 1110).
  • the report 1100 may be filtered to show data before and after a weight change separately.
  • the body weight data may be helpful for the healthcare provider to, for example, determine whether weight change may at least in part have been a basis for user modifications to target glucose levels.
  • the automated glucose level control system 510 e.g., using blood glucose readings
  • the subject 512 may feel differently.
  • the ability to collect the modification data relating to a user’s modification of the automated glucose level control system 510 and to correlate the data with weight changes can assist a healthcare provider in better treating the subject 512 by, for example, adjusting settings of the automated glucose level control system 510, changing insulin prescriptions, educating the subject 512, or any other action that may improve care of the subject 512.
  • the report may omit changes to blood glucose target settings that are below a threshold. In other words, minor changes that may be statistical noise may be ignored. Further, in some cases, the report may indicate when control parameters (e.g., at bedtime, with respect to a particular meal, such as dinner, etc.) are modified. In some cases, the report may also indicate the duration of the change to the glucose target setpoint, or other control parameter.
  • control parameters e.g., at bedtime, with respect to a particular meal, such as dinner, etc.
  • the report may also indicate the duration of the change to the glucose target setpoint, or other control parameter.
  • FIG. 12 illustrates an example meal selection report 1200 that may be included as part of some implementations of the control parameter modification report 1100 of FIG. 11 in accordance with certain embodiments.
  • the meal selection report 1200 may include a table 1202 identifying the average number of times per day that a user (e.g., the subject 512) announces each meal type. Typically, a user will announce a meal 0 or 1 times a day. However, in some cases, a user may announce a particular mealtime more than 1 time to account, for example, for large snacks that may be similar in size to a particular meal. Smaller snacks often may be handled by the control algorithm of the automated glucose level control system 510 (e.g., by the corrective insulin controller 626) without a meal announcement.
  • the automated glucose level control system 510 e.g., by the corrective insulin controller 626
  • the table 1202 may identify the number of times over the tracking period, or selected time period within the tracking period, that meals of particular sizes are announced by a user. For example, the table 1202 may indicate the number of times that a usual size meal is announced, a smaller than usual size meal is announce, or a larger than usual size meal is announced.
  • An ambulatory medical device may include a control system that autonomously provides therapy to a subject, for example, based on a health condition of a subject (e.g., determined based on one or more measured physiological indicators or parameters of the subject).
  • the control system may determine the therapy time and/or the intensity of the therapy during each therapy delivery based on one or more measured physiological parameters (e.g., using one or more subject sensors, such as a CGM sensor) and according to a predictive model that may include one or more control parameters.
  • the predictive model may be used to estimate a physiological effect of the therapy in order to adjust the therapy delivery according to an intended physiological effect.
  • the AMD may be an ambulatory medicament device that regulates the level of an analyte in subject’s blood.
  • an ambulatory medicament device is an automated glucose level control system (e.g., the glucose level control system 510) that may automatically provide insulin and/or a counter-regulatory agent (e.g., Glucagon) to a subject 512 to help control the glucose level (BGL) of the subject 512.
  • a counter-regulatory agent e.g., Glucagon
  • a control algorithm may be implemented by the automated blood level glucose level control system 510 to determine when to deliver insulin and/or how much insulin to provide to the subject 512. Further, the control algorithm may control both an ongoing or periodic delivery of insulin (e.g., a basal dose), and a correction bolus that may be provided to adjust a subject’s glucose level to within a desired range.
  • the control algorithm may use glucose level readings obtained from a subject sensor (e.g., a sensor measuring one or more physiological parameters of the subject in real time), such as a continuous glucose monitoring (CGM) sensor, that obtains automated blood glucose measurements from the subject.
  • CGM continuous glucose monitoring
  • the control algorithm may deliver a bolus of insulin in response to an indication of a meal to be consumed or being consumed by the subject 512.
  • Insulin may be administered subcutaneously into blood of a subject 512.
  • the glucose level control system may subcutaneously deliver a medicament (e.g., insulin, glucagon) via an infusion set connected to a site on subject’s body.
  • a medicament e.g., insulin, glucagon
  • PK pharmacokinetic
  • pharmacodynamic (PD) delay there might be a delay , referred to as pharmacodynamic (PD) delay, between variation of the amount of insulin in the subject’s blood plasma and the resulting variation of glucose level in the subject’s blood.
  • the value of pharmacodynamic (PD) delay may be used to estimate BGL based on an estimated concertation of insulin in patient’s blood.
  • the glucose level control system may implement a predictive algorithm based on a pharmacokinetic (PK) model to estimate the accumulation of insulin in the blood plasma of the subject over time, following the subcutaneous administration of insulin to a subject.
  • PK pharmacokinetic
  • the PK delay may be subject specific and/or change overtime.
  • the PK model may include one or more parameters, referred to as control parameters, that may be subject specific and/or change overtime.
  • factors and parameters that may influence the PK delay and/or the control parameters of the PK model may include, type of insulin, glucose level (e.g., at the insulin administration time), physiological characteristics of the subject, health condition of the subject, one or more physiological parameters of the subject, time of the administration, location at which the infusion set is placed, the amount of insulin administered and the like.
  • the physiological characteristics may include characteristics shared among large portions of the population (e.g., weight, gender, age, etc.) as well as characteristics that may be unique or specific to the subject, or shared among few people (e.g., characteristics related to genetics). Differences between the physiologies of different subjects may result in differences in the optimal blood glucose range for each subject, or some subset of subjects.
  • the glucose level control system 510 may implement a method to adaptively change the one or more control parameters in of the PK model used in its control algorithm to modify its predictions, in order to maintain the BGL within a desired range.
  • the glucose level control system may use readings from one or more subject sensors (e.g., a CGM) and/or information received from the subject (e.g., using a user interface of the AMD), to modify one or more control parameters.
  • a blood glucose system such as an automated glucose level control system 510, may control delivery or administering of insulin, or a counter -regulatory agent, based on a PK model and one or more glucose level measurements of the subject.
  • the PK model can be a bi -exponential PK model that may be used to estimate or determine the absorption or accumulation of subcutaneously administered insulin into blood and/or a decay rate of the insulin level in the subject’s blood for a given value of delivered dose of insulin.
  • the absorption of insulin over time according to a bi-exponential PK model may be represented by the following equation: where Uo is the subcutaneous dose in units (U), K is a scaling constant, and ai and 012 are time constants that may be used as the control parameters of the model.
  • Tmax the peak time of absorption of insulin, starting from the time that subcutaneous dose (Uo) is administered, may be referred to as Tmax and can be determined based on the following equation:
  • Tmax alone may be used as the control parameter of the bi -exponential PK model.
  • Tmax may be referred to the time at which the concentration of insulin in subject’s blood reaches a maximum level (e.g., starting from the time that subcutaneous dose is administered).
  • the bi -exponential PK model may be used to estimate or determine the accumulation of counter-regulatory agent or hormone (e.g., glucagon) in subject’s blood.
  • Equation 2 may be used to calculate the pending effect of the accumulated amount of insulin in the subcutaneously administered dose, as that can be taken to be the difference between the total area (/ 0 ⁇ p(t)dt, which can describe a measure of the total amount of hormone (e.g., insulin) that can be absorbed due to a dose Uo) and which can represent a measure of the expended portion of Uo at time.
  • hormone e.g., insulin
  • the glucose level control system is configured to maintain a subject’s blood glucose within a particular range (e.g., a desired or predetermined range).
  • a glucose level control system may administer particular amounts of insulin or counter-regulatory agent to the subject to bring the glucose level of the subject back to within a desired range or closer to a desired setpoint.
  • a PK model e.g., the bi-exponential PK model
  • the PK model (e.g., the bi-exponential PK model) may be used to predict the concentration of insulin glucose level of the subject over time as insulin or counter-regulatory agent is administered.
  • the control parameter values of the PK model may be set by a healthcare provider based on default values obtained through clinical trials and/or based an individualized treatment plan for the subject as may be determined based on clinical tests of the subject and/or on the healthcare provider’s evaluation of the subject, which may be determined based on tests of the subject.
  • the pharmacokinetic delay and the control parameters of the PK model may be subject specific and/or change overtime due to various factors.
  • clinical data may determine optimal or recommended values of the control parameters for an average subject through one or more trials, the determined data may not be optimal for a particular subject.
  • individualized treatment plans are typically based on point-in-time measurements. These point-in-time measurements may provide a good guideline for treatment, but the optimal values of the control parameters for a subject may vary at different times of day, due to different activities, due to changes in the subject over his or her lifetime, or for any other number of reasons.
  • the glucose level control system 510 of the present disclosure can implement a method or process to autonomously and/or automatically modify one or more control parameters of a control algorithm, or the model used by the control algorithm, to modify therapy provided to the subject using the glucose level control system 510.
  • the method may be performed by a hardware processor 530 and/or a controller 518 that controls the administering of therapy.
  • the system can provide therapy (e.g., insulin) to a subject in response to a determination of a glucose level of the subject.
  • the glucose level may be determined based at least in part on a glucose level signal obtained from a glucose sensor that is operatively connected to a subject.
  • the determination of the therapy may be based at least in part on the glucose level and/or the bi-exponential model. Moreover, the determination of therapy may be based at least in part on a value or setting of one or more control parameters of the glucose level control system.
  • the one or more control parameters may be, or may correspond to, one or more parameters of the bi-exponential PK model, or any other model or control algorithm used to control the administering of therapy to the subject.
  • the system 510 may provide the therapy based on the value or setting of the one or more control parameters.
  • the value or setting of the one or more control parameters may be based on an initial configuration of the glucose level control system 510 by a healthcare provider, subject, or other user. Further, the initial configuration may be based on clinical data or data obtained that is specific to the subject.
  • a control parameter may be a time constant used by a control algorithm of the glucose level control system (e.g., Tmax in a bi-exponential PK model). This time constant may be used in a calculation of an accumulation of insulin in the subject by the control algorithm.
  • control parameter may be used to control an insulin dosing response of the control algorithm to a blood glucose excursion in the subject as indicated by a glucose level signal obtained from a glucose sensor.
  • control parameter may be, or may be related to, Tmax (e.g., defined by equation 2).
  • the control parameter may be an estimate of Tmax or a fraction (e.g., 0.5) of Tmax.
  • Tmax may be the peak time of absorption of insulin, or the amount of time until the concentration of insulin from an insulin dose reaches maximum concentration in the blood of the subject.
  • control parameter may be associated with a setpoint or target glucose level, or a blood glucose range.
  • the control parameter could relate to a point in time when an estimated amount of “insulin on board” (e.g., an amount of insulin in the subject as determined by a model of insulin accumulation and/or utilization in the subject) falls below a threshold value.
  • the control parameter can be a clearance time for insulin boluses (e.g., an estimate of an amount of time for an administered bolus of insulin to be utilized by the subject).
  • the control parameter may relate to Tl/2, which corresponds to a time when the concentration of insulin in the blood plasma reaches half of the maximum concentration in the blood plasma.
  • the control parameter may be a parameter that can be used to calculate Tmax or Tl/2.
  • the system 510 may determine an effect of the supplied therapy (herein referred to as therapy effect or effect).
  • the therapy effect may be determined by analyzing a glycemic control of blood glucose (e.g., variation of BGL or supplied therapy over a measurement period) in the subject’s blood as indicated by the glucose level signal received from the glucose sensor (e.g., a CGM sensor).
  • the control system may measure or determine the effect of the supplied therapy over time.
  • the therapy effect may be determined based on variation of BGL and/or the amount of therapy delivered over time.
  • the system may continue to supply therapy to the subject over several therapy delivery times or instances and may average or otherwise aggregate the measured or determined effects of the therapy over the several therapy delivery times or instances.
  • the system 510 may determine the therapy effect based at least in part on an input received from the subject.
  • the input received from the subject may include a subjective or objective effect.
  • the input received from the subject may include manual glucose level measurements obtained using, for example, test strips.
  • Another example of input may be an indication of light-headedness, difficulty breathing, headaches, or any other objective or subjective effect identified by the subject.
  • the control system 510 may autonomously determine a modification to one or more control parameters. For example, the control system may modify Tmax value used by the control algorithm (or the PK model used in the control algorithm), for example, to improve the effect of a subsequent therapy that may be provided to the subject.
  • the directional modification e.g., increase or decrease
  • the control parameter value may depend on the measured or determined effect of the therapy provided based on the initial or prior value of a control parameter.
  • the directional modification of the control parameter value may depend on a difference between the determined or measured effect of the blood glucose therapy and an expected effect of the blood glucose therapy (e.g., calculated based on PK model). In some examples, the directional modification of a control parameter may be determined based on the amount of therapy doses provided and/or measured BGL of the subject, during and between one or more previous therapy deliveries.
  • the pharmacodynamic delay for a subject may be a known value.
  • the amount of absorbed insulin in the subject’s blood may be estimated based on the measured value of BGL received from a glucose sensor.
  • the directional modification may depend on the difference between calculated value of absorbed insulin based on a PK model (e.g., bi -exponential PK model) with a selected value of Tmax, and the estimated value of the absorbed insulin based on the measured value of BGL received from a glucose sensor.
  • the system 510 may determine therapy to deliver to the subject 512 at a therapy delivery time.
  • therapy may be delivered during one or more therapy delivery times based on the modified control parameter.
  • the system may determine the effect of the therapy delivered based on the modified control parameter using one or more of the embodiments previously described with respect to the therapy delivered using the initial control parameter.
  • the control system can compare the measured, determined or reported effects (e.g., physiological effects) from the therapy delivered using the initial value of a control parameter and those from the therapy delivered using the modified value of the control parameter. Based on the comparison, the control system may determine which values of the control parameter is preferable for the subject. In some examples, the comparison may be performed in real-time, or substantially in real-time. Further, the comparison may be performed by the system 510 without user interaction. The comparison may be performed using a comparison method and based on one or more comparison criteria.
  • the measured, determined or reported effects e.g., physiological effects
  • the comparison method may be based on finite number of therapy effects determined or measured at discrete times or based on continuous temporal variations of an effect over a period.
  • the comparison method may involve statistical analysis of the measured or determined effects resulting from usage of the initial value and modified value of the control parameter.
  • the comparison criterion may be based on the effects or based on the temporal variations of the effects over a period.
  • the preferable control parameter value can be a value that causes the glucose level of the subject to stay within a desired range or closer to a setpoint level for the subject. Accordingly, the system can set or maintain the control parameter to have the value that generated glucose levels that are closer to the desired range or setpoint for the subject for subsequent therapy.
  • the system 510 may repeat the process for different control parameter values enabling the system to refine the glucose level control for the subject over time.
  • the initial control parameter value may not be an initial value but may be the most recent selected value for the control parameter based on the determined effects of the control parameter.
  • the determination of a second or modified value for a control parameter, or the modification of the control parameter may be triggered based on a glucose level of the subject not satisfying a threshold.
  • a process of modifying a control parameter value may be triggered based on a difference between an expected glucose value of a subject and an expected glucose value of a subject after the administering of therapy exceeding a threshold.
  • the value of a control parameter may be autonomously modified without interaction by a subject or user with the glucose level control system.
  • the glucose level control system can automatically adjust and/or refine a control parameter used by a control algorithm for glycemic control of the subject.
  • the glucose level control system may provide both insulin therapy and counter-regulatory agent therapy to a subject.
  • the glucose level control system may only provide insulin therapy.
  • the glucose level control system may output an indication of an amount of counter-regulatory agent that may or should be administered to the subject based on a detected condition of the subject.
  • the active control parameter value used by the control parameter may remain active until a subsequent occurrence of the therapy modification process.
  • performance of the therapy modification process is continuously performed with the control parameter value being modified based at least in part on a determined effect of the prior control parameter value.
  • the therapy modification process is performed until the determined effect of the therapy satisfies a desired threshold (e.g., when the detected glucose level is within a threshold of a setpoint or median setpoint value).
  • the therapy modification process is performed a set amount of times and the control parameter value that provides the best outcome (e.g., closes to desired glucose level) is set as the active control parameter for subsequent therapy.
  • providing therapy at different sites on the subject’s body may result in different blood glucose absorption rates (associated with different PK delays).
  • the therapy modification process may be performed each time the infusion set used to deliver the therapy is moved to a different site on the subject.
  • FIG. 13 presents a flowchart of an example automated glucose level control refinement process in accordance with certain embodiments.
  • the process 1300 may be performed by any system that can autonomously and/or automatically modify a control algorithm and/or a control parameter that affects execution of the control algorithm based on feedback (e.g., from a blood glucose signal) relating to therapy administered to a subject 512.
  • the process 1300 may be performed by one or more elements of the glucose level control system 510.
  • at least certain operations of the process 1300 may be performed by a separate computing system that receives blood glucose data from the glucose level control system 510.
  • one or more different systems may perform one or more operations of the process 1300, to simplify discussions and not to limit the present disclosure, the process 1300 is described with respect to particular systems.
  • the process 1300 may be performed automatically and without user interaction.
  • a user may trigger the process 1300 via a command or interaction with a user interface.
  • the process 1300 may be performed automatically.
  • the process 1300 may be performed continuously, periodically, or in response to a trigger.
  • the trigger may be time based and/or based on a measurement of the glucose level of the subject.
  • the trigger may correspond to a determination that a glucose level of a subject differs by more than a threshold from a predicted glucose level that is predicted by a glucose level control algorithm based on the administering of medicament.
  • the trigger may be based on the activation or first-time use of the glucose level control system 510 by the subject 512.
  • the process 1300 begins at block 1302 where the glucose level control system 510 receives a glucose level signal corresponding to the glucose level of a subject 512.
  • the glucose level signal may be received from a glucose sensor capable of measuring the level of glucose in the blood of the subject.
  • the sensor may be a continuous glucose monitoring (CGM) sensor.
  • CGM continuous glucose monitoring
  • the block 1302 can include one or more of the embodiments described herein with respect to the block 802 or 902.
  • the glucose level control system 510 provides a first therapy during a first therapy period to the subject 512.
  • the first therapy may be based at least in part on the glucose level signal and a first value of a control parameter.
  • the control parameter may include any control parameter that affects operation of the glucose level control system 510 and/or performance of a control algorithm of the glucose level control system 510.
  • the control algorithm may include any control algorithm used to determine a dose of medicament (e.g., insulin) to administer to the subject 512.
  • the controller 518 or the processor 530 may use the control algorithm to generate a dose control signal based at least in part on a value (e.g., the first value of the block 1304) of the control parameter to cause the delivery device 514 to administer a dose of insulin or other medicament.
  • a value e.g., the first value of the block 1304
  • control algorithm may be based on the PK model (equation 2).
  • control parameter may be Tmax, which may be calculated using equation 3.
  • control parameter may be Tl/2, which may relate to the amount of time for the dose of insulin in the blood stream to drop to 1 ⁇ 2 of the maximum concentration in the blood attributable to the dose administered to the subject 512.
  • the control parameter corresponds to a time until insulin within blood plasma of the subject reaches a particular concentration level subsequent to administration of an insulin dose.
  • the control parameter may be a parameter that affects the determination of Tmax, such as one or more of the time constants al and a2.
  • control parameter may be used by the control algorithm to account for and/or determine an accumulation of insulin (or other medicament) in the subject 512 and/or a rate of diminishment of the insulin (or other medicament) in the subject 512.
  • control parameter may be used to control an insulin dosing response of the control algorithm to a blood glucose excursion in the subject as indicated by the glucose level signal received at the block 1302.
  • the control parameter may relate to at least one time constant used in a calculation of an accumulation of insulin in the subject by the control algorithm, such as one or more of the time constants al and a2 that may be used in the calculation of Tmax.
  • the control parameter may correspond to a rate of insulin diminishment in the subject 512.
  • the control parameter may relate to a target setpoint or a target setpoint range for maintaining or attempting to maintain the subject’s 512 glucose level.
  • the first therapy may correspond to a single administering of insulin to the subject 512. This single administering of insulin may be any type of insulin administered for any reason.
  • the insulin dose may be a basal insulin dose, a priming dose, a dose supplied in response to a meal announcement, or a correction dose of insulin.
  • the first therapy may be medicament other than insulin, such as counter -regulatory agent (e.g., glucagon).
  • the first therapy may be a plurality of medicament (e.g., insulin and/or counter-regulatory agent) doses supplied or administered to the subject 512 over the first therapy period.
  • the plurality of medicament doses may include a variety of types of medicament doses, such as one or more basal doses, one or more meal doses associated with one or more meal announcements, one or more corrective doses, etc.
  • the first therapy period may be a time period that corresponds to a single medicament dose.
  • the first therapy period may be a time period that encompasses a plurality of medicament doses.
  • the time first therapy period may be a time period associated with a defined length of time.
  • the first therapy period may be defined based on a number of medicament delivery periods. In other words, the time period may vary based on the amount of time it takes to deliver or administer a specified number of doses of medicament (of any type or of a particular type).
  • the first value may be selected based on a prior therapy or a prior performance of the process 1300. In some cases, the first value is selected based on a baseline value. The baseline value may be associated with clinical data, or it may be determined based on initial operation of the glucose level control system 510 for some period of time before performance of the process 1300. Alternatively, or in addition, the first value may be selected based on clinical data or a particular prescription for the subject 512. In some cases, the first value may be based on clinical data for average users or average users that share certain physiological data with the subject 512. In some cases, the first value is determined based on a healthcare provider’s assessment of the subject 512.
  • the first value may be determined based on an infusion site (e.g., back, stomach, leg, etc.) for the glucose level control system 510. In some cases, the first value may be selected based on demographics or characteristics of the subject 512. For example, the first value may be based on the subject’s 512 gender, weight, body mass, or age.
  • the glucose level control system 510 determines a first effect corresponding, or attributable, at least in part to the first therapy. Determining the first effect may include receiving a glucose level signal from the glucose sensor operatively connected to the subject. This glucose level signal may be a subsequent or updated glucose reading that is more recent than the glucose level signal received at the block 1302. The glucose level signal received at the block 1302 may be used to determine therapy to administer to the subject 512 and the glucose level signal received at the block 1306 may be used to determine a result of the administered therapy. It should be understood that glucose level signals may be received continuously or periodically and can be used to both determine therapy to administer and to determine the effect of the administered therapy.
  • determining the first effect may include analyzing glycemic control of blood glucose in the subject as indicated by the glucose level signal. Analyzing the glycemic control of the blood glucose in the subject may include tracking the glucose level of the subject 512 over time. Further, analyzing the glycemic control of the blood glucose in the subject may include comparing the glucose level of the subject 512 over time to a predicted blood glucose for the subject 512 over time as predicted based on the PK model used in the control algorithm using the selected value for the control parameter. As mentioned above, in some examples, the measured glucose level of the subject 512 over time may be used to calculate the accumulation and/or diminishment of the insulin level in subject’s blood.
  • analyzing the glycemic control of the blood glucose in the subject may include determining whether, or to what degree, the calculated accumulation and/or diminishment of insulin (or other medicament) using the PK model (e.g., bi -exponential PK model) and the control parameter values used in the control algorithm matches the accumulation or diminishment of insulin (or other medicament) estimated based on the measured glucose level (e.g., obtained from the CGM sensor).
  • the first effect may, at least partially, be determined by analyzing one or more signals received from one or more subject sensors that measure one or more physiological parameters of the subject (e.g., heart rate, temperature and the like).
  • the first effect may be determined based on an input received from the subject (e.g., using a user interface of the AMD). In some cases, the first effect may be determined based at least in part on an assessment or input provided by the subject 512 (e.g., using a user interface) with respect to the first value or the first effect. For example, if the subject 512 feels woozy, dizzy, lightheaded, nauseous, or otherwise uncomfortable during the first therapy period, the subject 512 may, via, for example, a touchscreen display of the AMD, indicate how the subject 512 is feeling.
  • the glucose level control system 510 obtains a second value for the control parameter.
  • This second value may be autonomously determined. Further, in some cases, the second value may be automatically determined. In some cases, the second value is determined based at least in part on a user triggering the glucose level control refinement process 1300. In some such cases the control system may determine the second value and present it to the user via a user interface circuitry 534 of the control system 510.
  • the second value may be obtained from a user interface circuitry 534 of the glucose level control system 510 (e.g., in response to a user interaction with the user interface).
  • the second value may be obtained from a computing system that is connected to or otherwise in communication with the glucose level control system.
  • the communication connection may be a wired or wireless connection.
  • the wireless connection may be a direct connection (e.g., via Bluetooth or other near field communication technologies) or a connection over a network (e.g., a local area network, a wide area network, a cellular network, etc.).
  • the second value may be an increase or decrease of the control parameter compared to the first value.
  • the second value may be limited to a particular maximum change from the first value.
  • the second value may be selected based at least in part on the first effect. For example, if the first effect corresponding to the first value results in blood glucose being near an upper range of the setpoint range, the second value may be selected in an attempt to being the glucose level closer to the middle of the setpoint range. Further, the second value may be selected based at least in part on characteristics of the subject 512, such as age, weight, gender, or any other characteristics that may affect blood glucose management.
  • the second value may be selected based at least in part on the first effect determined based on an assessment provided by the subject 512, in an attempt to reduce the symptoms felt by the subject 512.
  • the second value of the control parameter may be generated based at least in part on a baseline value of the control parameter and an output of a function defined based on glycemic control of the subject.
  • the glycemic control of the subject may include the measured value of the glucose level in subjects blood (e.g., provided by the CGM) and/or the amount of therapy (e.g., dose of insulin or counter -regulatory hormone) provided during the first therapy period.
  • the baseline value of the control parameter may correspond to the first value used to provide therapy at the block 1304. This baseline value may be a last known optimal value for the subject prior to any changes to the subject (e.g., change in weight, insulin type, or metabolism changes, etc.). Alternatively, or in addition, the baseline value may be a value determined by a healthcare provider. In some cases, the second value of the control parameter is based at least in part on glycemic control indicated by the glucose level signal.
  • the second value may be a modification to Tmax or Tl/2. It should be understood that Tmax and/or Tl/2 may, at least in part, be based on the physiology or biochemistry of the subject 512.
  • the setting of either Tmax or Tl/2for the setting of the first value and the second value may refer to setting a parameter of the control algorithm or the PK model used by the control algorithm, representative of or corresponding to Tmax and/or Tl/2.
  • the setting of the first value and the second value may include setting one or more control parameters that may be used to determined or estimate Tmax and/or Tl/2 for the subject 512.
  • the set value may differ from the actual value of Tmax and/or Tl/2 for the subject 512.
  • Tmax and/or Tl/2 may vary for different subjects, it is not always possible to explicitly set or determine Tmax and/or Tl/2 for a subject. Instead, Tmax and/or Tl/2 may be estimated or determined by comparing the effects and/or glucose levels determined for different control parameter values that correspond, at least in part, to Tmax and/or Tl/2.
  • the control parameter may iteratively approach the actual Tmax and/or Tl/2 for the subject 512, or within a threshold of the actual Tmax and/or Tl/2 for the subject 512.
  • the control parameter (such as one or more of the time constants al and a2) may iteratively approach a value that corresponds to the actual Tmax and/or Tl/2 for the subject 512.
  • the glucose level control system 510 changes the control parameter to the second value.
  • Changing the control parameter to the second value causes a change in the operation or execution of the control algorithm.
  • This change in the execution of the control algorithm may result in a change in one or more factors associated with the provisioning of therapy to the subject 512.
  • the changing in the execution of the control algorithm may result in a change in an amount of medicament delivered, a timing of the delivery of the medicament, a rate at which a dose of medicament is delivered to the subject 512, a target setpoint or target range for the blood glucose of the subject, a threshold used in determining whether to deliver medicament (e.g., a threshold difference from the target setpoint), or any other factor that may affect therapy delivered to the subject 512.
  • the glucose level control system 510 provides second therapy during a second therapy period to the subject 512.
  • the second therapy is based at least in part on the updated control parameter that is updated to the second value at the block 1310.
  • the second therapy may refer to one or a plurality of medicament doses.
  • the second therapy period may refer to a specific amount of time, an amount of time to deliver a particular number of medicament doses, or a particular number of medicament doses.
  • the block 1312 may include one or more of the embodiments described with respect to the block 1304 but using the second value for the control parameter over the second therapy period.
  • the duration of the second therapy period may be equal to the duration of the first period.
  • the number of therapies delivered during the second therapy period may be equal to the number of therapies delivered during the first second therapy period.
  • the glucose level control system 510 determines a second effect corresponding at least in part to the second therapy.
  • the block 1314 may include one or more of the embodiments described with respect to the block 1306, but with respect to the second therapy.
  • the glucose level control system 510 selects one of the first value or the second value based at least in part on a comparison of the first effect and the second effect.
  • the comparison of the first effect and the second effect may be performed autonomously without action by a user.
  • the glucose level control system 510 may select the one of the first value or the second value to be a current or active value for the control parameter based on whether the first effect or the second effect results in improved care (e.g., closer to a desired setpoint for a greater period of time, or less volatility in blood glucose values, or any other factor that a healthcare provider may use to evaluate the success of diabetes management) for the subject 512.
  • the glucose level control system 510 selects a third value to the current or active value for the control parameter.
  • the third value may be selected based on the comparison of the first effect and the second effect. For example, if it is determined that the first effect is preferable to the second effect, the third value may be selected based on a change to the first value in the opposite direction as the change made to the first value to obtain the second value.
  • the first value corresponded to a Tmax of 60 minutes
  • the second value was selected to correspond to a Tmax of a longer time period (e.g., 65 or 70 minutes)
  • the third value may be selected to correspond to a Tmax of a shorter time period (e.g., 50 or 55 minutes).
  • Comparing the first effect and the second effect may include determining whether the first value or the second value brought the subject’s 512 glucose level closer to a target setpoint and/or maintained the subject’s 512 glucose level within a target range for a longer period of time. In some cases, comparing the first effect and the second effect may include determining whether the first value or the second value resulted in a more stable glucose level for the subject 512 or less volatility in the glucose level of the subject 512. In some cases, comparing the first effect and the second effect may include determining whether the first value or the second value resulted in more and/or greater excursions of the subject’s 512 glucose level from a target blood glucose range.
  • Comparison of the first effect and the second effect may be performed in real-time or substantially in real-time accounting for the processing speed of the hardware processor 530 or the glucose level control system 510. Thus, in some cases, the comparison of the first effect and the second effect may be performed upon determination of the second effect. [0325] In some embodiments, the comparison of the first effect and the second effect may include a statistical comparison or statistical analysis of the first effect and the second effect. In some cases, the comparison of the first and second effects may include determining whether the second therapy produced a statistically significant improvement in therapy (e.g., glycemic control) compared to the first therapy. A statistically significant improvement may vary depending on the subject or the condition of the subject.
  • a statistically significant improvement may vary depending on the subject or the condition of the subject.
  • the comparison can also include a determination of whether there was a statistically significant increase in risk factors (e.g., hypoglycemia) during the second therapy period compared to the first therapy period.
  • a statistically significant improvement may be an improvement determined based on a first statistical analysis of a set of data associated with the first effect and a second statistical analysis associated with the second set of data associated with the second effect.
  • the first and second statistical analysis may include calculating the mean and variance of the glucose levels measured during the first and second therapy periods, respectively.
  • an improvement may be determined by comparing the mean value and the variance of the glucose levels measured during the first and second therapy periods.
  • an improvement may be determined by comparing the mean value and the variance of the glucose levels measured during the first and second therapy periods with one or more reference values.
  • the reference values may be values provided by a health care provider or a user and may be stored in the memory 540 of the glucose level control system 510.
  • the first and second therapy period may be long enough to include a plurality of therapy deliveries (e.g., infusion of glucose and/or glucagon) during each period.
  • an improvement may be determined by comparing by other statistical quantities calculated at least in part based on the glucose levels measured during the first and second therapy periods.
  • the statistical quantities may be specific statistical quantities defined for comparing the effects of a therapy (e.g., medicament delivery for controlling the glucose level in a subject).
  • the first and/or second may be output to user (e.g., the subject or a parent) via a user interface of the glucose level control system and/or a computing system (e.g., a smartphone, laptop, personal computer, or the like).
  • the user may use the determined effect to adjust the value of a control parameter.
  • the value that better manages the subject’s 512 blood glucose may be output to a user (e.g., the subject or a parent).
  • the user may then configure the glucose level control system 510 based on the selected control parameter value.
  • the glucose level control system 510 may automatically modify the value of the control parameter.
  • the user may be provided with an opportunity to confirm the modification.
  • the modification may occur automatically without confirmation.
  • the modification may be presented to the user (e.g., the subject or a healthcare provider) and/or logged in a therapy log.
  • the comparison is performed by another computing system that is in communication with the glucose level control system 510.
  • the glucose level control system 510 may transmit the glucose level signal, data determined from the glucose level signal, and/or the assessment received from the subject, indicative of the effect of the glucose level control, to another computing system, such as a local computing system, a smartphone, or a cloud-based computing system.
  • the glucose level control system 510 may transmit data associated with the control parameters values and the administering of medicament to the subject 512 to the computing system.
  • the computing system may determine the value of the control parameter that better manages the subject’s 512 glucose level.
  • the computing system may configure the glucose level control system 510 with the selected value. Alternatively, or in addition, the selected value may be output to a user who can configure the glucose level control system 510 with the selected value.
  • the glucose level control system 510 provides therapy to the subject 512 based on the selected value for the control parameter that is selected at the block 1316.
  • the therapy provided at the block 1318 may be provided during a third therapy period that is at some point after the first and second therapy periods.
  • the first and second values may be used, respectively, for the control parameter to determine the value that results in the better outcome or improved care for the subject 512.
  • the value that resulted in the better outcome for the subject 512 may be used to provide future care for the subject 512.
  • a new value that is neither the first or second value may be used to provide subsequent care in an attempt to find a value for the control parameter that may provide a better or improved level of care (e.g., closer to a desired target glucose level for a longer period of time) for the subject 512.
  • providing therapy to the subject may include generating a dose control signal to a delivery device 514 (e.g., infusion pump coupled by catheter to a subcutaneous space of the subject 512) that delivers an amount of a medicament (e.g., insulin or a counter-regulatory agent) to the subject wherein the amount may be determined by the dose signal.
  • a delivery device 514 e.g., infusion pump coupled by catheter to a subcutaneous space of the subject 512
  • a medicament e.g., insulin or a counter-regulatory agent
  • Providing therapy to the subject 512 based on the selected value may include configuring the glucose level control system 510 to provide therapy to the subject 512 during a third therapy period based at least in part on the active control parameter value.
  • configuring the glucose level control system 510 to provide therapy to the subject 512 based at least in part on the active control parameter value may end the process 1300.
  • the process 1300 may be repeated. Repeating the process 1300 may include using the selected value (e.g., the first or second value from a prior iteration of the process 1300) as the first value when performing the operations associated with the block 1304.
  • the second value generated at the block 1308 may be a new value not used during the prior iteration of the process 1300.
  • the process 1300 may be repeated until a difference between the first effect and the second effect is less than a threshold difference. Alternatively, or in addition, the process 1300 may be repeated a particular number of iterations, periodically, in response to a command, or in response to determining that the subject’s 512 blood glucose does not satisfy a particular threshold for a particular amount of time.
  • the process 1300 may be used to modify more than one control parameters of a glucose system (or a control algorithm used by the control system) .
  • the process 1300 may be used to adjust a first control parameter during a first modification period starting from block 1302 and ending at block 1318, and to adjust a second control parameter during a second modification period again starting from block 1302 and ending at block 1318.
  • the second modification period may be immediately after the first modification period or delayed by a particular time.
  • the control system may determine when a second control parameter should be modified following the modification of a first parameter.
  • the delay may be determined at least in part based on the measured glycemic control based on the glucose signal (e.g., received from a CGM sensor). In some other examples, the delay may be determined based on input received from a user. In some examples, the modification of the second control parameter may be at least partially determined based on the determined modification of the first control parameter. [0334] In some examples, a third control parameter may be adjusted during a third time period after adjusting the first and the second control parameters. The adjustment of the third control parameter may immediately follow the adjustment of the second control parameter or may occur after a delay. The delay may be determined at least in part based on the glycemic control of the subject after the second control parameter is adjusted.
  • the glucose level control system may be configured to sequentially adjust the first and second, or the first, second and third control parameters when the glycemic control of the subject satisfies one or more threshold conditions. In some examples, the duration of the time period during which a control parameter is adjusted may defer from that of the other parameters.
  • a modified version of the process 1300 may be used to determine a value (e.g., an optimal value) of a control parameter. In some such examples, after determining the second effect at block 1314, the control system may skip block 1316 and block 1318, and instead obtain a third value for the control parameter. In some examples, this third value may be determined at least in part based on the determined second effect at block 1314.
  • this third value may be autonomously determined. Further, in some cases, the third value may be automatically determined. In some cases, the third value is determined based at least in part on a user triggering the glucose level control refinement process 1300. In some such cases the control system may determine the third value and present it to the user via a user interface circuitry 534 of the control system 510. In some examples, the third value may be provided by a user via a user interface circuitry 534 of the control system 510. In some examples, after obtaining the third value, the system may provide therapy to the subject based on the third value.
  • This modified version of process 1300 may be repeated several times. In some examples, this modified version may be repeated until a difference between the last two subsequent effects is less than a threshold difference.
  • the modified version of the process 1300 may be repeated a particular number of iterations, periodically, in response to a command, or in response to determining that the subject’s 512 blood glucose does not satisfy a particular threshold for a particular amount of time.
  • the process 1300 may be used to modify one or more control parameters that affect the delivery of insulin.
  • the process 1300 is not limited as such and may be used to modify one or more control parameters that affect the delivery of other medicaments, such as counter-regulatory agent (e.g., glucagon, dextrose, etc.).
  • the process 1300 may be used to recommend a change in insulin and/or counter- regulatory agent delivery without modifying the delivery. This can be advantageous for generating recommendations regarding counter-regulatory agent in a single hormone glucose level control system 510 that does not support counter -regulatory agent, or that supports the use of counter-regulatory agent, but does not have the counter-regulatory agent available.
  • the at least two or more of the control parameters may be related to each other.
  • the control parameters include the time constants al and a2
  • a2 may equal 1.5 times al
  • the value for the control parameter set as the active parameter (e.g., the first value or the second value) at the block 1316 may be used by the control algorithm to provide therapy to the subject 512 for a particular period of time or until the process 1300 is repeated.
  • the process 1300 is repeated periodically and/or in response to a trigger, such as a blood glucose value or an average blood glucose value over a time period, or an indicate of a site change for the connection of the glucose level control system 510 to the subject 512 (e.g., a change in the location of the infusion set used to provide the subcutaneous dose).
  • the peak time of absorption of insulin may be referred to as Tmax.
  • Different types of insulin may result in different amounts of time until peak absorption into the subject’s blood or for different subjects.
  • the aggregate Tmax among subjects for the fast-acting insulin lispro and insulin aspart may be determined to be approximately 65 minutes, while the aggregate Tmax among subjects using ultra-fast-acting insulin, such as, for example, the insulin aspart injection marketed under the Fiasp brand, which has a formulation to decrease time to peak absorption, may be determined to be approximately 40 minutes.
  • Tmax is held constant while varying the type of insulin used.
  • mean glucose drops when Tmax is lowered when using the ultra-fast acting insulin.
  • three cohorts of subjects employ control algorithms that use modified Tmax values when using a glucose level control system with ultra-fast-acting insulin such as Fiasp.
  • the first cohort uses a glucose level control system configured with a Tmax of 65 minutes for a first week of therapy and a lower Tmax (such as, for example, 50 minutes) for a subsequent week of therapy.
  • the second cohort uses the glucose level control system configured with a Tmax of 65 minutes for the first week of therapy and an even lower Tmax (such as, for example, 40 minutes) for a subsequent week of therapy.
  • the third cohort uses the glucose level control system configured with a Tmax of 65 minutes for the first week of therapy and a sharply lower Tmax (such as, for example, 30 minutes) for a subsequent week of therapy.
  • Comparison of the change in Tmax within each cohort and across cohorts demonstrates that the mean glucose level drops when Tmax is lowered, and there is no statistically significant increase or decrease in hypoglycemia.
  • Tmax is shorter than physiological insulin absorption peak time
  • the glucose level control system may stack or administer multiple doses of insulin within a time period. This may occur because the glucose level control system may incorrectly identify a lower blood glucose concentration as a maximum glucose level concentration when Tmax is set below the actual peak insulin absorption time.
  • the control system may determine whether there is a statistically significant difference in mean glucose level during a later period using a different Tmax value compared to an earlier evaluation period.
  • Tmax or a control parameter of the glucose level control system 510 corresponding to Tmax may be set to the newer value, where the change in the control parameter value may occur automatically upon determination of a statistically significant improvement or may occur after generating a notification of the potential improvement and receiving confirmation that the change in control parameter value should occur.
  • the value for Tmax may be lowered by a significant amount from the initial Tmax.
  • control algorithm may automatically change Tmax or an associated time constant to reflect a Tmax reduction of at least 10 minutes, at least 5 minutes, at least 2 minutes, no more than 15 minutes, no more than 20 minutes, no more than 30 minutes, or by a change within a range spanning between any two of the preceding values in this sentence, where the preceding values are included in the range.
  • the system can perform a statistical analysis between the prior data set associated with the higher Tmax, and the current data set associated with the lower Tmax.
  • the system can adopt or recommend the lower Tmax value as the preferred Tmax. This process can be repeated using additional reductions in Tmax. In some cases, each reduction in Tmax may be smaller than the previous reduction. Moreover, if it is determined that there is a not an improvement in the mean glucose level for the subject and/or if there is an increase in hypoglycemia or hypoglycemia risk events, the system may use the prior Tmax or may select a Tmax between the new Tmax and the prior Tmax. Thus, using the process 1300, the system can iteratively modify Tmax to find an optimal value for the subject and/or the selected insulin type.
  • a significant or statistically significant improvement e.g., more than a threshold improvement
  • the real-time process and statistical analysis described herein can be used to analyze other types of biomedical data obtained by one or more subject sensors (e.g., measuring one or more physiological parameters).
  • the additional biomedical data such as data may be received from a smartwatch (e.g., blood pressure, heart rate), from a weight sensor, or any other type of biomedical sensor.
  • the outcomes of the comparative analysis described herein may be used to make additional recommendations to the subject. For example, if it is determined that the actual Tmax for a particular type of insulin is higher than expected for the subject, it may be recommended that the subject modify his or her diet in a particular manner while using that particular type of insulin.
  • Embodiments of an automated glucose level control system 510 that can be adapted for use with embodiments of the present disclosure are described in International Publication No. WO 2015/116524, published on August 6, 2015; U.S. Patent No. 9,833,570, issued on December 5, 2017; and U.S. Patent No. 7,806,854, issued on October 5, 2010, the disclosures of each of which are hereby incorporated by reference in their entirety for all purposes.
  • the automated glucose level control system 510 can autonomously administer insulin doses and account for online accumulation of insulin doses (“insulin on board”) due to the finite rate of utilization of the insulin.
  • the rate the insulin absorption, and in turn accumulation, of insulin doses may be modeled by a pharmacokinetic (PK) model (e.g., the bi-exponential PK model represented by equation 2 with preset values of time constants al and a2).
  • PK pharmacokinetic
  • the peak time for insulin absorption in blood is referred to as Tmax.
  • Tmax may be the time at which the concentration of insulin reaches its maximum value following the delivery of a specific dose of insulin.
  • Tmax may be measured from the time that insulin is provided to the subject (e.g., subcutaneously using an infusion set).
  • setting the time constants in the PK model may be equivalent to setting Tmax that is inherently assumed by the model; conversely, setting Tmax may set the time constants of the PK model. Since the values of the time constants may be used to determine the online calculation of the accumulation of insulin by a control system, the value of the time constants may consequently control the control system’s insulin dosing response to a given glucose level excursion. Thus, varying Tmax or time constants associated with Tmax controls the aggressiveness of the control system’s insulin doses.
  • the control system implements a method to adapt the control system’s PK model’s Tmax (hence time constants) setting online. This method may be performed either by the control system periodically making online assessments and calculations that produce recommendations of modifications in Tmax or by the control system autonomously modulating Tmax online. In either case, the calculations may be based on the control system’s performance over some time period. In some cases, adaptations to Tmax online, whether autonomously occurring or issued as recommendations can be based on the glucose-control performance by the control system over some time interval, including trends in glucose level, mean glucose level, or extent and/or duration of low glucose level (hypoglycemia) and/or high glucose level (hyperglycemia) occurrence.
  • the calculation can be based on the usage of a counter-regulatory agent, the otherwise intended usage of a counter-regulatory agent had it been available (e.g., in insulin-only systems or in cases where the counter-regulatory agent or its delivery channel are temporarily unavailable).
  • the method can impose upper and/or lower (static or dynamic) bounds for the range over which the Tmax can vary.
  • the degree of adaptation in Tmax for a given situation can be different depending, for example, on the specific insulin being administered by the control system.
  • the described method may be applicable regardless of whether the continuous glucose monitor (which can provide the input glucose signal to the control system) is online or offline.
  • the method disclosed herein can be applied to system described in International Publication No. WO 2015/116524.
  • the described method can coexist with other aspects of the system being activated or not, such as, but not limited to, having a glucose target that is adapted automatically by the system, e.g., as in the system described in International Publication No. WO 2017/027459, published on February 16, 2017, which is hereby incorporated by reference herein for all purposes.
  • the absorption of subcutaneously administered insulin into blood may be governed by the bi -exponential PK model of equation 2.
  • Setting the time constants in the PK model may set a measure of the pending effect of the accumulated amount of insulin in the subcutaneously administered dose, as that can be taken to be the difference between the total area (J 0 ⁇ p(t)dt, which can describe a measure of the total action over time due to a dose U0) and which can represent a measure of the expended portion of U0.
  • the peak time, Tmax, of the absorption of insulin doses into blood may be given by equation 3.
  • setting Tmax may set the PK model time constants, which can directly govern the magnitude (e.g., aggressive or conservative) of the control system’s online insulin dosing response to a given glucose profile.
  • the bi -exponential PK model may be used to simulate the relation between a glucose profile and the medicament (e.g., insulin or glucagon) doses delivered to a subject.
  • FIGS. 14A-14C illustrate a simulation demonstrating an effect that increasing or decreasing the Tmax setting, or value for a control parameter corresponding to Tmax, may have on the glucose level control system’s 510 online insulin and glucagon dosing response to a given glucose profile (e.g., temporal variation of glucose level over 24 hours).
  • FIG. 14A illustrates a simulation of glucose level control of a subject with Tmax set to 65 minutes.
  • the graph 1402 illustrates the variation of glucose level (BGL) of a subject over 24 hours.
  • the range 1404 indicates the desired target setpoint range (e.g., between 70 and 120 mg/dL) for the subject’s glucose level.
  • the range 1406 indicates the range in glucose level (e.g., below 60 mg/dL) for the subject that is associated with hypoglycemia or a risk of hypoglycemia.
  • the graph 1410A illustrates the administering of medicament (insulin or glucagon) to the subject over the same 24 -hour time period as graph 1402 based at least in part on the glucose level variation illustrated in the graph 1402.
  • FIG. 14B illustrates a simulation of glucose level control of a subject with Tmax set to 15 minutes.
  • the graph 1410B corresponds to the graph 1410 A, but with Tmax set to 15 minutes instead of 65 minutes. As illustrated by comparing the graph 1410B to 1410A, reducing Tmax to 15 minutes may result in an increase in insulin dosing required to maintain the given glucose profile 1400.
  • FIG. 14C illustrates a simulation of glucose level control of a subject with Tmax set to 130 minutes.
  • the graph and 1410C corresponds to the graph 1410A, but with Tmax set to 130 minutes instead of 65 minutes.
  • increasing Tmax to 130 minutes may result in a decrease in insulin dosing required to maintain the given glucose profile 1400.
  • glucose profile of a subject is unchanged, increasing or decreasing insulin (or counter-regulatory agent) dosing may affect care of the subject 512.
  • the subject may experience different degrees of symptoms (e.g., dizziness, nausea, etc.) attributable to maintenance of the subject’s diabetes.
  • autonomous optimization of one or more control parameters of a glucose level control system may reduce the amount and/or frequency of the medicament doses required to maintain a normal glucose profile.
  • FIGS. 14A-14C illustrate one non-limiting example of the impact of modifying a control parameter of a glucose level control system.
  • different dosing may subsequently lead to different blood glucose excursions which in turn may vary the determined insulin-glucagon doses subsequently.
  • the simulations shown in FIGS. 14A-14C demonstrate the correlation between Tmax as a control parameter and the determined medicament doses by the glucose level control system 510 for each therapy. Further these simulations demonstrate that the determined therapy doses may be used as a feedback to adjust Tmax as descried below.
  • the value of Tmax can be varied automatically online based on glycemic control in a receding time period.
  • Tmax can be described using the following the equation:
  • T max W T ax + f ⁇ y k ,g k ), (4)
  • T ⁇ ac is a baseline value of Tmax
  • f(y k ,g k ) is a parameter control adjustment function (herein referred to as adjustment function), based on glycemic control of the glucose signal, y k , and/or the amount of counter-regulatory dosing, g k , that is computed by the control system (whether delivered or not).
  • Evaluation of f(y k> 9 k ) could be over a time period (e.g., one week, two weeks, four weeks or other time intervals).
  • k may represent a current therapy period and N may indicate a receding time period that may include one or more therapy periods.
  • the parameter control adjustment function f(y k ,g k ) can cause an increase in T max (k ) relative to T ⁇ ac for an increase in hypoglycemia (in severity and/or duration) or impending hypoglycemia in glycemic control of the glucose signal, y k , over the receding time period (that may include one or more therapy periods) and, conversely, can cause a decrease in T max (k ) relative to T ⁇ ax for an increase in hyperglycemia (in severity and/or duration) in glycemic control of the glucose signal, y k , over the receding time period.
  • f(y k , g k ) can cause an increase or decrease in T max (k) relative to T ⁇ ac respectively for an increase or decrease in amount of counter-regulatory dosing, g k , over the receding time period.
  • the adjustment f(y k ,g k ) to T max (k) can be evaluated and effected at discrete times, which can be at scheduled periodic intervals (e.g., once every 24 hours, once every three days, once a week, etc.), in response to a user command, or based on a physiological measurement of the subject.
  • adjustments can be evaluated and effected online when some metric satisfies a threshold or meets certain criteria within the current computation window (e.g., a week, a month, etc.). This criterion can include when hypoglycemia in y k reaches or crosses a certain threshold or the level of counter -regulatory dosing in g k reaches or crosses a certain threshold.
  • the adjustment can be affected after some evaluation related to the glucose signal y k (e.g., mean value) in the current computation window has attained a statistically significant difference from its evaluation in a preceding computation window (e.g., the week before).
  • therapy periods can be scheduled regular or periodic time intervals (e.g., 24 hour periods, two day periods, one week periods, etc.), based on a user command, or based on a physiological measurement of the subject.
  • therapy periods may be defined as the time interval between two subsequent therapy deliveries, and each therapy period may be identified based on the therapy delivery time that marks the beginning of the therapy period.
  • G(t) 1502 e.g., a CGM trace received from a CGM sensor
  • a therapy period starting from tS 1504 and ending at tE 1506
  • one or several doses of insulin and/or a counter -regulatory agent e.g., glucagon
  • an insulin dose of Ui 1508 units may be provided at time tu,i 1510 at a measured glucose level of Gu,i 1512 (where i varies from 1 to the number of insulin deliveries between tS 1504 and at tE 1506).
  • control system may have calculated a dose of Cj 1514 units, that may have been administered or not, a glucose level Gcj 1518 at which glucagon may have been delivered and the time tcj 1516, at which glucagon may have been delivered, (where j varies from 1 to the number of glucagon deliveries between tS 1504 and at tE 1506).
  • the control system may be configured to provide therapy in order to maintain the BGL within a desired or predetermined range defined by an upper bound Gmax 1520 and a lower bound Gmin 1522 and close to a setpoint Gset 1524.
  • the glucose levels above Gmax 1520 may indicate hyperglycemia and glucose levels below Gmin 1522 may be considered hypoglycemia.
  • two instances of hyperglycemia 1526 and two instances of hypoglycemia 1528 may be identified by the control system.
  • the control system may store G(t) 1502, tu,i 1510, tcj 1516, Ui 1508 and Cj 1514, for all therapy deliveries (all values of i and j).
  • the value of one or more control parameters e.g., Tmax, Gset
  • FIG. 16 presents a flowchart of an example automated blood glucose refinement process that may use the above-mentioned modification method to control Tmax and/or other control parameters of a glucose level control system.
  • the process 1600 may be performed by any system that can autonomously and/or automatically modify a control algorithm and/or a control parameter that affects execution of the control algorithm based on feedback (e.g., from a blood glucose signal) relating to therapy administered to a subject 512.
  • the process 1600 can serve as a first intervention (or first mode) for maintaining a glucose level within a predetermined range, such as between a maximum glucose level and a minimum glucose level.
  • the process 1600 may be performed by one or more elements of the glucose level control system 510. In some cases, at least certain operations of the process 1600 may be performed by a separate computing system that receives blood glucose data from the glucose level control system 510. Although one or more different systems may perform one or more operations of the process 1600, to simplify discussion and not to limit the present disclosure, the process 1600 is described with respect to particular systems.
  • the process 1600 may be performed automatically and without user interaction.
  • a user may trigger the process 1600 via a command or interaction with a user interface.
  • the process 1600 may be performed automatically.
  • the process 1600 may be performed continuously, periodically, or in response to a trigger.
  • the trigger may be time based and/or based on a measurement of the glucose level of the subject.
  • the trigger may correspond to a determination that a glucose level of a subject differs by more than a threshold from a predicted glucose level that is predicted by a glucose level control algorithm based on the administering of medicament.
  • the trigger may be based on the activation or first-time use of the glucose level control system 510 by the subject 512.
  • the process 1600 begins at block 1602 where a first value is selected for a control parameter (e.g., a control parameter that may be adaptively modified) of the glucose level control system 510.
  • the control parameter can be a Tmax value used in the control algorithm of the glucose level control system 510.
  • Tmax may be related to one or more parameters in a PK model used by the control algorithm.
  • the control parameter can be a setpoint (e.g., Gset 1524 in FIG. 15) or the target value for the measured value of the blood glucose concentration of a subject 512 (e.g., measured using a CGM sensor).
  • the first value of the control parameter may be selected based on a baseline value.
  • the baseline value may be associated with clinical data, may be determined based on operation of the glucose level control system 510 for some period of time before performance of the process 1600, or may be determined from a prior performance of the process 1600.
  • the baseline value may be selected based on clinical data or a particular prescription for the subject 512.
  • the baseline value may be based on clinical data for average users or average users that share certain physiological data with the subject 512.
  • the baseline value is determined based on a healthcare provider’s assessment of the subject 512.
  • the baseline value may be determined based on an infusion site (e.g., back, stomach, leg, etc.) for the glucose level control system 510.
  • the baseline value may be selected based on demographics or characteristics of the subject 512.
  • the glucose level control system 510 provides therapy over a time period to the subject 512. based at least in part on the first value of the control parameter. Further, the therapy may be provided based at least in part on one or more glucose signals received during the time period.
  • the glucose signals may be received from a glucose sensor (e.g., a CGM) and may correspond to a glucose level of the subject.
  • the time period may include one or more therapy periods. In some examples, the number of therapy periods included in the time period may be equal or unequal therapy periods.
  • a therapy period may be a time period that corresponds to a single delivered medicament dose, which may include an instantaneous delivery or a delivery of the medicament dose over a period of time.
  • a therapy period may be a time period that encompasses a plurality of medicament dose deliveries. Further, a therapy period may be a time period associated with a defined length of time. Alternatively, or in addition, the therapy period may be defined based on a number of medicament periods. In other words, the time period may vary based on the amount of time it takes to deliver or administer a specified number of doses of medicament (of any type or of a particular type).
  • the time of delivery and dose of the plurality of therapies may be based at least in part on the glucose level signal and the first value of a control parameter of the control algorithm used by the glucose level control system 510.
  • the control parameter may include any control parameter that affects operation of the glucose level control system 510 and/or performance of a control algorithm of the glucose level control system 510.
  • control parameter can be Tmax, Tl/2, speed of delivery of a medicament dose, a setpoint for the glucose level, a blood glucose range, a threshold value of glucose level (e.g., a maximum or minimum value) and the like.
  • the control algorithm may include any control algorithm and/or PK model used to determine a dose of medicament (e.g., insulin) to administer to the subject 512.
  • the controller 518 or the processor 530 may use the control algorithm to generate a dose control signal based at least in part on a value (e.g., the first value selected at the block 1602) of the control parameter to cause the delivery device 514 to administer a dose of insulin or other medicament.
  • Each therapy of the plurality of the therapies provided over the time period may correspond to a single administering of insulin to the subject 512.
  • This single administering of insulin may be any type of insulin that may be administered for any reason.
  • the insulin dose may be a basal insulin dose, a priming dose, a dose supplied in response to a meal announcement, or a correction dose of insulin.
  • each therapy provided may be a medicament other than insulin, such as counter-regulatory agent (e.g., glucagon).
  • each therapy delivery may include a plurality of medicament (e.g., insulin and/or counter-regulatory agent) doses supplied or administered to the subject 512 over a therapy period.
  • the plurality of medicament doses may include different types of medicament doses, such as one or more basal doses, one or more meal doses associated with one or more meal announcements, one or more corrective doses, etc.
  • the value of the control parameter that is being adjusted may change from one therapy period to another therapy period during the time window.
  • the value of the control parameter may change by a given amount in the beginning of each therapy period or group of therapy periods.
  • the value of the control parameter may change by a given amount after certain number of therapies.
  • the amount by which the control parameter is changed may be determined based on one or more receding therapy periods in the time window.
  • the block 1604 may include one or more of the embodiments described with respect to the process 1300.
  • therapy data may be obtained and/or stored.
  • therapy data may include the glucose signal, G(t) 1524, the calculated or actual delivery time (tcj 1516) and the estimated or delivered amount of a counter-regulatory agent (Cj 1514).
  • This therapy data may be stored in the memory 540 of the glucose level control system 510. Further, the therapy data may include a total amount of the counter-regulatory hormone administered during a therapy period. Alternatively, or in addition, other parameters and data associated with each therapy period may be stored in the memory 540.
  • the total amount of insulin administered an amounts of insulin delivered (Ui 1508), a delivery time (tu,i 1510) of the insulin delivered during each therapy period, data received from other sensors that may measure one or more physiological parameters of the subject, data received from the subject or user (e.g., via a user interface), and the like.
  • the glucose level control system 510 determines a control parameter adjustment for the control parameter.
  • the control parameter adjustment may be based at least partially on the therapy data.
  • the adjustment may be determined using an adjustment function.
  • the adjustment function may be the function fiy ⁇ g ⁇ ) for modifying Tmax according to equation 4.
  • the control parameter adjustment may be determined by analyzing glycemic control of blood glucose in the subject as indicated by the glucose level signal (e.g., G(t) 1524 or the CGM trace). Analyzing the glycemic control of the blood glucose in the subject may include tracking the glucose level of the subject 512 over time.
  • analyzing the glycemic control of the blood glucose in the subject may include comparing the glucose level of the subject 512 over time to a predicted blood glucose for the subject 512 over time estimated based on the PK model and control parameter values used in the control algorithm.
  • the value of the adjustment function fiy ⁇ g ⁇ ) may be calculated at least in part using the estimated or actual values of tcj 1516, Cj 1514, and Gcj, (where j varies from 1 to the number of counter- regulatory provided during the time period).
  • determination of the adjustment function fiy ⁇ g k may include a statistical analysis based on the estimated or actual values of tcj 1516, Cj 1514, and Gcj, (where j varies from 1 to the number of counter- regulatory provided during the time period).
  • the statistical analysis may be based on statistical quantities and/or the analytical tools described herein.
  • the adjustment to the control parameter may be determined based on the number of hypoglycemia 1528 and/or hyperglycemia 1526 events and/or duration of each event. In some examples, the adjustment to the control parameter may be determined based on the difference between measured glucose level and the setpoint (Gset 1524). In some examples, the adjustment may be determined based on the time intervals during which the glucose level stays within a target range (e.g., between Gmax 1520 and Gmin 1522). In some cases, the adjustment may be determined based on the stability of the measured glucose level for the subject 512 or less volatility in the glucose level of the subject 512. For example, a statistical analysis may be performed to determine the distribution rate of change for G(t) beyond one or more threshold rates.
  • the adjustment to the control parameter may, at least partially, be determined by analyzing one or more signals received from one or more subject sensors that measure one or more physiological parameters of the subject (e.g., heart rate, temperature and the like).
  • the adjustment to the control parameter may be determined based on an assessment or input received from the subject 512 (e.g., using a user interface of the AMD). For example, if the subject 512 feels woozy, dizzy, lightheaded, nauseous, or otherwise uncomfortable during one or a plurality of therapy periods, the subject 512 may, via, for example, a touchscreen user interface or other interface of the AMD, indicate how the subject 512 is feeling.
  • the adjustment may be determined in real-time or substantially in real-time accounting for the processing speed of the hardware processor 530, the glucose level control system 510, or the time for the subject to provide an assessment of his or her condition to the glucose level control system 510.
  • the adjustment to the control parameter may be determined by a computing system that is in communication with the glucose level control system 510.
  • the glucose level control system 510 may transmit the therapy data, to another computing system, such as a local computing system, a smartphone, or a cloud- based computing system.
  • the glucose level control system 510 may transmit the therapy data and data associated with the control parameters values to the computing system.
  • the computing system may determine the adjustment that better manages the subject’s 512 glucose level in the next time period.
  • the glucose level control system 510 adjusts the control parameter using the control parameter adjustment determined at the block 1606.
  • the adjustment may be performed autonomously or automatically.
  • the control parameter adjustment determined at block 1606 may be presented to the subject or other user (e.g., parent, guardian, clinician, etc.) via a user interface (e.g., a touchscreen display).
  • the subject or other user may be able to confirm or modify the control parameter adjustment.
  • the display of the control parameter adjustment may be presented for informational purposes and may not be adjustable by a user.
  • the control parameter may be adjusted only after receiving the user confirmation (e.g., a user interaction with a user interface).
  • the adjustment value may be presented to user via a user interface of the glucose level control system or a user interface of the computing system.
  • the user may adjust the control parameter of the glucose level control system using the adjustment value received from or presented by the computer system.
  • the adjustment at block 1608 may cause a change in the operation or execution of the control algorithm.
  • This change in the execution of the control algorithm may result in a change in one or more factors associated with the provisioning of therapy to the subject 512.
  • the change in the execution of the control algorithm may result in a change in an amount of medicament delivered, a timing of the delivery of the medicament, a rate at which a dose of medicament is delivered to the subject 512, a target setpoint or target range for the blood glucose of the subject, a threshold used in determining whether to deliver medicament (e.g., a threshold difference from the target setpoint), or any other factor that may affect therapy delivered to the subject 512.
  • the adjusted value of the control parameter may be output to a user (e.g., the subject or a parent).
  • the user may then configure the glucose level control system 510 based on the selected control parameter value.
  • the glucose level control system 510 may automatically adjust the value of the control parameter.
  • the user may be provided with an opportunity to confirm the adjustment.
  • the adjustment may occur automatically without confirmation. However, the adjustment may be presented to the user (e.g., the subject or a healthcare provider) and/or logged in a therapy log.
  • the glucose level control system 510 provides therapy based at least in part on the updated control parameter that is updated at the block 1608.
  • the new value of the control parameter may be maintained during a second time period.
  • the second time period may refer to a specific amount of time, an amount of time to deliver a particular number of medicament doses, or a particular number of medicament doses.
  • the process 1600 may be repeated during subsequent time periods.
  • the process may be repeated periodically (every 24 hours, every two days, every week, or other time intervals).
  • the time period may be provided by the subject or a user.
  • the process may be repeated in response to a command.
  • the process may be repeated in response to determining that the subject’s 512 glucose level does not satisfy one or more criteria for a particular amount of time. For example, the process may be repeated when a statistically significant difference between the measured mean value of the BGL and a target BGL exceeds a threshold, or a number of hypoglycemia and/or hyperglycemia detected exceeds a threshold number during a specific amount of time.
  • the process 1600 may be used to adjust several control parameters that affect the therapy delivery by the glucose level control system.
  • the process 1600 may be used to adjust a first control parameter during a time period and to adjust a second control parameter during a second time period.
  • the second time period may be immediately after the first time period or delayed by a particular time.
  • the control system 510 may determine when to adjust the control parameter.
  • a delay between periods of control parameter adjustment may be determined at least in part on the glycemic control of the glucose signal. In some cases, the delay may be determined based on input received from a user. Further, the adjustment of the second control parameter may be at least partially determined based on the determined adjustment for the first control parameter.
  • a third control parameter may be adjusted during a third time period.
  • the adjustment of the third control parameter may immediately follow the adjustment of the second control parameter or may occur after a delay.
  • the delay may be determined at least in part based on the glycemic control of the subject after the second control parameter is adjusted.
  • the glucose level control system may be configured to sequentially adjust the first and second, or the first, second, and third control parameters when the glycemic control of the subject satisfies one or more threshold conditions.
  • the duration of the time period during which a control parameter is adjusted may differ from that of the first and second control parameters.
  • the process 1600 may be used to adjust one or more control parameters that affect the delivery of insulin.
  • the process 1600 is not limited as such and may be used to modify one or more control parameters that affect the delivery of other medicaments, such as a counter-regulatory agent (e.g., glucagon).
  • the process 1600 may be used to recommend a change in insulin and/or counter -regulatory agent delivery without modifying the delivery. This can be advantageous for generating recommendations regarding counter-regulatory agent in a non-bi-hormonal glucose level control system 510 that does not support counter-regulatory agent, or that supports the use of counter-regulatory agent, but does not have the counter-regulatory agent available.
  • a value (e.g., a baseline value or optimal clinical value) of one or more control parameters of a PK model and/or control algorithm used by a glucose level control system 510 may be determined by statistical analysis of therapy data sets (e.g., glycemic control information) collected from multiple cohorts of subjects (e.g., 20, 50, 100, 200 subjects) during a clinical study.
  • the control parameter e.g., Tmax
  • Tmax may be directly measured for the subjects within each cohort (e.g., based on results of blood analysis following manual or automated medicament administrations). These measurements may be used to determine an optimal value of a control parameter (e.g., Tmax) to be used in a glucose level control system.
  • the glucose level (BGL) of the subjects may be controlled and recorded for a given period (e.g., one week, two weeks, one months, or other periods) using identical or nearly identical glucose level control systems.
  • the subjects in each cohort may use the same values for a control parameter of the glucose level control system while the subjects in different cohorts may use different values of the same control parameter.
  • the measured therapy data sets, (e.g., comprising measured and/or determined glycemic control information for the subjects) over the given period may be compared using statistical analysis to evaluate an optimal value of the control parameter.
  • the measured glycemic control of subjects in a first cohort in response to setting Tmax to a first value may be compared to the measured glycemic control of subjects in a second cohort in response to setting Tmax to a second value.
  • Such comparison may include various statistical analysis that can reveal statistically significant differences between measured glycemic controls.
  • the mean value, variance and/or standard deviation of the measured glucose level data obtained from the first and second cohort may be compared to a set of reference values that may be obtained from a third cohort of subjects with normal glucose level (e.g., nondiabetic subjects).
  • Such clinical studies often require several cohorts each comprising a large number of subjects (e.g., large enough to produce enable statistical analysis) and therefore large number of identical glucose level control systems. For example, in some studies 10, 20, 50, or 100 subjects and glucose systems may be required. As such, determining the optimal value of one or more control parameters based on clinical studies can be expensive and time consuming. Moreover, clinical studies typically cannot capture unique physiological characteristics of and real-time physiological changes of a subject (even studies include several large cohorts).
  • a portable glucose level control system that monitors the BGL in real time and autonomously or automatically provides medicament to a subject, may collect and store therapy data sets that, similar to those collected in clinical studies, may include sufficient number data points for a statistical analysis.
  • therapy data may include glycemic control information (e.g., received from a CGM sensor), other physiological effects of the therapy (e.g., obtained from subject sensors or the subject), an amount and type of medicament delivered, medicament delivery times, and the like.
  • these therapy data sets may be used to determine an optimal value of one or more control parameters of the glucose level control system or a value for the one or more control parameters of the glucose level control system that provides improved diabetes management compared to a default value, baseline value, or initial clinically determined value.
  • the optimal or improved values may be determined based on statistical analysis, including the type of statistical analysis that may be used in clinical studies.
  • the statistical analysis may include calculating one or more statistical quantities such as mean, variance, standard deviation, various statistical distributions (e.g., those described with respect to FIG. 17) and the like.
  • On board and real-time (or near real-time) evaluation of values of one or more control parameters of a glucose level control system based on therapy data collected during one or more therapy periods eliminates the need for expensive and time consuming clinical studies and may improve the maintenance of a subject’s diabetes by, for example, taking into account unique physiological characteristics of and real-time physiological changes of a subject.
  • on board evaluation of control parameter values provides for faster and more accurate diabetes evaluation and management compared to clinical testing.
  • the therapy data collected by a glucose level control system may include glycemic control information, information related to medicament delivery times, doses of medicament provided, the BGL level at the time of medicament delivery (e.g., measured based on a glucose signal obtained from a CGM sensor), the physiological effects of the medicament on a subject (e.g., BGL in a time period after medicament delivery, subjects assessment and the like), and any the type of data that may be determined from therapy provided to the subject.
  • the glucose level control system may collect therapy data during one or more therapy periods.
  • the collected and stored therapy data during each therapy period may include, but is not limited to: a CGM trace G(t) 1502, delivered doses (Ui 1508) and delivery times (time tu,i) of insulin, delivered or determined doses (Ci 1514) and delivery times (tc,i 1516), of a counter-regulatory agent (e.g., glucagon) and the like.
  • the therapy data may be stored in a memory (e.g., a flash drive, a solid-state drive, a hard disk, or any other type of non-volatile memory) of the glucose level control system as one or more data sets. Each data set may be associated with one or more categories of therapy data or a specific therapy period during which the therapy data was collected.
  • the value of the one or more control parameters may change from one therapy period to another therapy period. For example, the value of the control parameter may change by a given amount in the beginning of a therapy period or a group of therapy periods. The value of the control parameter may be changed automatically by the glucose level control system 510 or by a user via a user interface.
  • control parameter may be changed by a given amount after certain number of therapy periods.
  • the amount by which the control parameter is changed may be determined based on therapy data collected during one or more preceding therapy periods. Alternatively, or in addition, the amount by which the control parameter is changed may be provided by a user via a user interface.
  • the duration of one or more therapy periods is selected such that the measured or determined data sets are sufficiently large for statistical analysis.
  • an uncertainty associated with an optimal or improved value of a control parameter determined using statistical analysis may depend on the size of the data set used for the analysis.
  • the process 1300 may be used to determine a value (e.g., an optimal value) of a control parameter using statistical analysis. For example, statistical analysis may be used to determine the therapy effects at blockl306, block 1314, or to compare the therapy effects resulting from different control parameter values at block 1316.
  • the second value of the control parameter may be provided by the user (e.g., the subject or the guardian) based at least in part on the first effect and outcomes of the statistical analysis performed on the therapy data collected and/or stored during the first therapy period (block 1304).
  • a statistical analysis may be performed based at least in part on the first effect and the second effect to obtain a comparative assessment.
  • the comparative assessment may be used to determine whether one of a pair or set of values of a control parameter results in an improved glycemic control of the subject compared to the other values used for the control parameter.
  • the determined value of the control parameter at block 1316 may be provided to the subject, a guardian or a healthcare provider via a user interface of the glucose level control system 510 and/or a computing system (e.g., a smartphone, a notebook a personal computer and the like) connected to the glucose level control system (e.g., via a wireless link).
  • the subject, the guardian or the healthcare provider may change the value of the corresponding control parameter to the determined value by an interaction with a user interface before the next therapy period (e.g., at block 1318).
  • the glucose level control system 510 may automatically change value of the control parameter to the determined value and proceed to block 1318.
  • the user may be provided with an opportunity to confirm the modification.
  • the modification may occur automatically without confirmation.
  • the modification may be presented to the user (e.g., the subject or a healthcare provider) and/or logged in a therapy log.
  • the first and second therapy provided to the subject during the first (block 1304) and second (block 1312) therapy periods may include a plurality of therapy deliveries.
  • a first and second first therapy data may be obtained by the control system 510.
  • the therapy data may comprise glycemic control information that at least includes the glucose signal received during the corresponding therapy period.
  • Determining the first effect may include calculating statistical characteristics of the therapy data collected during the plurality of therapies provided during each period. For example, the control system 510 may calculate the mean value, deviation from mean value, and the variance of the measured BGL.
  • control system 510 may calculate one or more quantities (e.g., statistical quantities) to quantify the average glucose level and its deviation from a baseline level. In some embodiments, the control system 510 may determine one or more quantities (e.g., statistical quantities) to evaluate the variability of glycemic control and the associated risks (e.g., risk of hypoglycemia or hyperglycemia) or quantify the average glucose level and its deviations from a baseline (e.g., normal) level. In some cases, the duration of the second period may be equal to the duration of the first period. Alternatively, or in addition, the duration of each period may be selected such that each period includes the same number of therapies provided to the subject.
  • the duration of each period may be selected such that the number of times therapy is administered during the time period is large enough to enable statistically significant assessments.
  • the comparison between the first effect and the second effect may include statistical analysis of statistical data generated based on the data collected during the first and second period.
  • control system may generate a control parameter optimization report that may include the statistical quantities calculated during the optimization process. Further, the report may include a graphical representation of the therapy data and related risk assessments. In some such examples, this report may be used by the subject or a healthcare provider to make decisions related to selecting a determined optimal parameter value. Additionally, the control parameter optimization report may include information that may be used by the subject or a healthcare provider to modify the overall strategy for managing the subject’s glycemic control. For example, modifying the mealtime, content or amount of meal consumed by the subject, and the like.
  • FIG. 17 illustrates some examples of statistical quantities that may be generated and utilized at blocks 1306 and 1314 of the process 1300, using the therapy data 1705 during a therapy period, and known parameters of the control system 1703.
  • the value of certain control parameter may be fixed and/or selected based on baseline values (e.g., outcomes of previous clinical studies) or a previously determined value (e.g., by a different control parameter modification and/or optimization process).
  • baseline values e.g., outcomes of previous clinical studies
  • a previously determined value e.g., by a different control parameter modification and/or optimization process.
  • Gmin 1722 lower bound for normal BGL
  • Gmax 1720 upper bound for normal BGL
  • Gset 1724 target BGL
  • Gmin 1722 may between 65mg/dL and 75 mg/dL
  • Gmax 1720 may be between 175 mg/dL and 185 mg/dL
  • Gset 1724 may be between 70 mg/dL and 180 mg/dL.
  • Gset 1724 may be a value (e.g., an optimal) determined by a previous optimization process (e.g., the process 1300).
  • G(t) 1702 (the CGM trance or the measured glycemic control), Ui ’s 1708, tu,i‘s 1710, Ci ’s 1514 and tc,i ’s 1716 may be included in the therapy data collected during the therapy period.
  • the therapy data 1705 may be used to generate various types of statistical quantities.
  • the therapy data 1705 may be used to generate probability distributions (e.g., discrete or continuous) and/or frequency distributions (e.g., absolute, relative, or cumulative) for certain measured or determined values.
  • the distributions associated with the glucose concentration 1726 e.g., portions of the therapy period during which the glucose signal was within selected ranges
  • glucose change rate 1728 e.g., portions of the therapy period during which the glucose change rate signal was within selected ranges rates
  • insulin dose 1730 percent of insulin doses provided within selected dose ranges
  • glucagon dose 1732 percent of glucagon doses provided within selected dose ranges
  • hyperglycemia 1734 percent of hyperglycemia events detected wherein the glucose signal was above Gmax by an amount within selected ranges
  • hypoglycemia 1736 percent of hypoglycemia events detected wherein the glucose signal was below Gmin by an amount within selected ranges
  • one or more characteristic of these statistical distributions may be used to determine (e.g., quantify) the effect of a therapy.
  • the therapy data considered to generate certain statistical data e.g., a histogram
  • time bins associated with these events may be specified by a user through a user interface.
  • the statistical analysis may comprise analytical methods and tools that can compare the effect of different control parameter values.
  • analytical methods and tools that can be used with one or more of the embodiments described herein are described in the article “Statistical Tools to Analyze Continuous Glucose Monitor Data” (W. Clarke et ak, Diabetes Technology and Therapeutics, vol. 11, S45-S54, 2009), which is hereby incorporated by reference in its entirety herein. Examples of methods and tools that may facilitate extraction of information from complex and voluminous measured glycemic control information during therapy periods, are discussed herein.
  • the therapy data used for statistical analysis includes the glucose trace of the subject or G(t).
  • G(t) may be a time-stamped series of glycemic data received from a CGM sensor (see FIG. 17).
  • the glucose signal obtained from CGM may represent glucose level as a discrete time series that approximates G(t) in steps determined by the resolution of the particular device (e.g., a reading every 2 min, 5 min, 10 min and the like).
  • statistical analysis may be performed on the therapy data (e.g., the glucose signal received from a CGM sensor) to provide an assessment (e.g., a comparative assessment) related to: (1) average glucose level and deviations from normal glycemic control (sometimes referred to as normoglycemia), (2) variability and risk assessment, and (3) clinical events, such as post-meal glucose excursions and hypoglycemic episodes.
  • the assessment may be made based on two sets of therapy data collected during two time periods.
  • the assessment may be used by the control system 510 to determine whether the glycemic control for a subject has been improved from a first therapy period to a second therapy period.
  • the assessment may be used by a health care provider to evaluate the glycemic control of a subject during one or more time periods.
  • the glucose level control system may determine three values of average blood glucose: the mean value (e.g., computed for the entire G(t) measured during a therapy period or part of a therapy period), a pre-meal mean value (e.g., computed for the time window of 60-120 min after the meal), and post-meal mean value (e.g., computed for the time window of 0-60 min before meal).
  • the mean value e.g., computed for the entire G(t) measured during a therapy period or part of a therapy period
  • a pre-meal mean value e.g., computed for the time window of 60-120 min after the meal
  • post-meal mean value e.g., computed for the time window of 0-60 min before meal.
  • the percentage of time within each range may be calculated via linear interpolation between consecutive glucose readings.
  • percentage of time within additional ranges can be computed.
  • the probability of occurrence of extreme hypoglycemia and hyperglycemia may be also evaluated.
  • standard deviation and variance may be used to compute variability of BGL.
  • a risk index may be defined that can serve as a measure of overall glucose variability when focusing of the relationship between glucose variability and risks for hypo- and hyperglycemia.
  • an individual function may be calculated to split the overall glucose variation into two independent sections related to excursions into hypo- and hyperglycemia, and at the same time equalize the amplitude of these excursions with respect to the risk they carry. For example, a BGL transition from 180 to 250 mg/dL may appear threefold larger than a transition from 70 to 50mg/dL, whereas if converted into risk, these fluctuations would appear equal.
  • analysis of BGL rate of change e.g., measured in mg/dL/min
  • the local properties may be assessed at a neighborhood of any point in time by the value BGL, its first or, sometimes, second derivatives (acceleration).
  • a statistical analysis of the user inputs provided during the first or second therapy period may be used in determining or comparing the therapy effects. For example, the number of times and time of the day that the subject has indicated certain symptoms, may be used to determining therapy effects.
  • a statistical analysis of the biomedical or physiological data received from one or more subject sensors may be used in determining or comparing the therapy effects.
  • subject sensors e.g., a smart watch, weight sensor, etc.
  • subject e.g., temperature, blood pressure, heart rate), from a weight sensor, or any other type of biomedical sensor.
  • the process 1300 may be modified to determine the optimal value of Tmax, or a value of Tmax that provides improved maintenance of the subject’s diabetes, by reducing Tmax (increasing the aggressiveness of the therapy) after each therapy period in a series of therapy periods, until a statistical assessment shows that further reduction of the Tmax does not improve the mean glucose level without increasing the probability of hypoglycemia.
  • Improved maintenance of the subject’s diabetes may include maintaining a mean glucose level closer to a setpoint glucose level range or reducing fluctuations in mean glucose level over time compared to prior control value (e.g., Tmax) settings. It should be understood that other metrics may be used to measure an improvement of maintenance of the subject’s diabetes, such as reduction in hypoglycemia risk events or reduction in administration of insulin without increasing diabetic effects or corresponding risks.
  • FIG. 18 presents a flowchart of an example automated control parameter refinement process in accordance with certain embodiments.
  • the process 1800 may be performed by any system that can autonomously and/or automatically modify a control algorithm and/or a control parameter that affects execution of the control algorithm based on feedback (e.g., from a blood glucose signal) relating to therapy administered to a subject 512.
  • the process 1800 may be performed by one or more elements of the glucose level control system 510.
  • at least certain operations of the process 1800 may be performed by a separate computing system that receives blood glucose data from the glucose level control system 510.
  • one or more different systems may perform one or more operations of the process 1800, to simplify discussions and not to limit the present disclosure, the process 1800 is described with respect to particular systems.
  • the process 1800 may be performed automatically and without user interaction.
  • a user may trigger the process 1800 via a command or interaction with a user interface.
  • the process 1800 may be performed automatically.
  • the process 1800 may be performed continuously, periodically, or in response to a trigger.
  • the trigger may be time based and/or based on a measurement of the glucose level of the subject.
  • the trigger may correspond to a determination that a glucose level of a subject differs by more than a threshold from a predicted glucose level that is predicted by a glucose level control algorithm based on the administering of medicament.
  • the trigger may be based on the activation or first-time use of the glucose level control system 510 by the subject 512.
  • the glucose level control system 510 may perform the process 1800 in order to adjust one or more control parameters of the glucose level control system 510 to improve the glycemic control of a subject.
  • the control parameter may include any control parameter that affects operation of the glucose level control system 510 and/or performance of a control algorithm of the glucose level control system 510.
  • the process 1800 may take into account the risk of hypoglycemia in the subject.
  • the process 1800 may include one or more of the embodiments described herein with respect to the process 1300.
  • the process 1800 begins at block 1802 where an initial value is selected for a control parameter of the glucose level control system (e.g., Tmax or other control parameters of the glucose level control system selected to be optimized).
  • the control parameter can be a control parameter of a pharmacokinetic (PK) model used by a control algorithm PK of the glucose level control system 510.
  • PK pharmacokinetic
  • the control parameter may be a time until insulin within blood plasma of the subject reaches a particular concentration level subsequent to administration of an insulin dose.
  • the initial value of the control parameter may be based on therapy delivered during a time period prior to the first therapy period, a clinical value, or a body mass of the subject.
  • the initial value of the control parameter may be selected using one or more of the embodiments described with respect to the block 1304 of the process 1300.
  • the control parameter may be a control parameter used by the control algorithm of the glucose level control system to account for accumulation of insulin in a subject.
  • the control parameter may be used to control an insulin dosing response of the control algorithm to a blood glucose excursion in the subject based on a glucose level signal received from a glucose sensor (e.g., a SGM sensor).
  • the control system 510 may provide therapy during a first therapy period based at least in part on the glucose level signal and the initial value of the control parameter.
  • the block 1804 can include one or more of the embodiments previously described with respect to the block 1304 of the process 1300.
  • the first therapy data may include glycemic control information resulting from the delivery of the first therapy.
  • the system may store all or some of the therapy data generated during the first therapy period in a memory of the control system 510.
  • the therapy provided at block 1804 may comprise a plurality of medicament deliveries.
  • the control system 510 may determine the therapy effect of the therapy provided during the first therapy period using statistical analysis of the first therapy data collected and stored at block 1804.
  • the statistical analysis may include calculating the statistical quantities discussed above and with reference to FIG. 17.
  • the statistical analysis may include regression analysis between certain measured and/or calculated parameters at block 1804.
  • the regression analysis may include determining an autoregression model.
  • the control system 510 may determine the therapy effect using one or more of the embodiments described with respect to the block 1306 of the process 1300.
  • the control system 510 may modify the value of the control parameter compared to the initial value selected at block 1802 or the value used in the last therapy period.
  • the modified value may be a value that makes the therapy more aggressive (e.g., aggressive by a significant amount). For example, when the control parameter is Tmax, at block 1808 the value of Tmax may be reduced to an amount less (e.g., 5, 10, 15 minutes, or more) than the value used in a previous therapy period (e.g., the initial value or the last modified value).
  • the modified value of the control parameter may be received from a user interface of the glucose level control system responsive to a user interaction with the user interface.
  • the previous therapy period may be the first therapy period or any earlier therapy period.
  • the value for Tmax may be lowered by a significant amount (e.g., 10 minutes, 15 minutes, or other values). Further, the amount by which Tmax is reduced may be smaller than a previous reduction during a previous iteration of the process 1800.
  • the control parameter may be modified automatically without action by a user. In some cases, modifying the control parameter may change a timing, a dosage size, or a speed of injection of insulin administered to the subject.
  • the control system 510 provides therapy to the subject based at least in part on the glucose signal and the modified value of the control parameter received from block 1808.
  • the duration of the therapy period (at block 1810), may be equal to the duration of one or more previous therapy periods. In some other examples, the duration of the therapy period may be determined based on the determined therapy effects of the therapies delivered during one or more previous therapy periods.
  • the system may store all or some of the therapy data generated during the therapy period.
  • the therapy provided at block 1810 may comprise a plurality of medicament deliveries.
  • the therapy data may include glycemic control information resulting from the delivery of the therapy.
  • the control system 510 determines the therapy effect of the therapy provided at block 1810 during the last therapy period.
  • the therapy effects may be determined based at least in part on the therapy data obtained and stored at block 1810.
  • the control system 510 may determine the therapy effect using one or more of the embodiments described with respect to the block 1306 of the process 1300.
  • the control system 510 performs a statistical analysis based at least in part in the determined therapy effect of the therapies provided and stored during the last therapy period and the therapy period before the last therapy period to obtain a comparative assessment. In some such examples the comparative assessment may be based on statistical analysis of determined effects and the therapy data collected during the corresponding therapy periods.
  • the statistical analysis may include generating statistical quantities (e.g., distributions shown in FIG 17) using the therapy data.
  • the statistical analysis may include the analytical method described herein.
  • one or more characteristics of the statistical data may be used to compare the therapy effects.
  • the statistical analysis may include calculating one or more of a mean, a median, a mode, a standard deviation, a rate, a ratio, or a probability based on the therapy data obtained in the last two therapy periods or the determined effects of the therapies provided during the last two periods.
  • the control system 510 may determine whether the value of the control parameter used during the last therapy period has improved the glycemic control for the subject compared to the therapy period before the last therapy period. In some embodiments, the control system 510 may determine whether the modified value for the control parameter has resulted in statistically significant improvement in glycemic control. In some embodiments, the control system 510 may determine whether the modified value for the control parameter has resulted in an improvement of a physiological parameter of the subject. In these embodiments, the physiological parameter may be determined based at least in part on the glucose level signal received from a glucose sensor.
  • control system 510 may return to the block 1810 and continue providing therapy to the subject based on the last modified value of the control parameter without any further modification.
  • the control system 510 determines that the value of the control parameter used during the last therapy period has improved the glycemic control for the subject compared to the therapy period before the last therapy period, the control system 510 proceeds to decision block 1818.
  • the improvement in the glycemic control should be larger than a threshold level before the system 510 proceeds to block 1818.
  • the control system proceeds to block 1818 if the modified value of the control parameter results in a reduced occurrence of blood glucose excursions compared to the first value of the control parameter.
  • the control system 510 may determine whether the frequency and/or severity of hypoglycemia events is increased during the last therapy period compared to the therapy period before the last therapy period. In some examples, if the control system 510 determines that the frequency and/or severity of hypoglycemia events is increased (e.g., beyond a threshold number or amount) during the last therapy period, the control system 510 may return to the block 1810 and continue providing therapy to the subject based on the last modified value of the control parameter without any further modification.
  • the control system may proceed to the block 1808 where the control system 510 modifies the value of the control parameter.
  • the modified value may be a value that results in more aggressive therapy (e.g., the value of Tmax may be reduced).
  • the amount by which the control parameter is changed may be smaller than a reduction amount in one or more previous modifications.
  • the control system may determine risks or the frequency and severity of one or more events other than hypoglycemia. For example, the control system may determine that in spite of an improvement in glycemic control for the subject, the rate and magnitude of glucose concentration has increased beyond threshold value. In some such examples, these additional risk determinations may be used to determine whether to keep or modify the last value of the control parameter.
  • a modified version of the process 1800 may be used by the glucose level control system wherein the process stops at block 1816 and the control system continues providing therapy based on the last modified value of the control parameter until a user input is received.
  • the last value of the control parameter (modified at block 1808), the results of the comparative assessment generated based on the comparison performed at block 1814 (e.g., whether a statistically significant improvement in subject’s glycemic control resulted from the last control parameter change)
  • the results of the comparative assessment generated based on the comparison performed at block 1814 may be output to the subject, a guardian or a healthcare provider via a user interface of the glucose level control system 510 and/or a computing system (e.g., a smartphone, a notebook a personal computer and the like) connected to the glucose level control system (e.g., via a wireless link).
  • the subject, the guardian or the healthcare provider may change the value of the corresponding control parameter (e.g., an interaction with a user interface) before the next therapy period.
  • the statistical analysis used to determine the therapy effects e.g., at blocks 1306 and 1312 in the process 1300, and block 1806 and 1812 in the process 1800) or to compare between therapy effects (e.g., at block 1316 in the process 1300 and block 1814 in the process 1800)
  • regression analysis may be used to find a relation between parameters calculated and/or measured during the therapy period. For example, with reference to FIG.
  • a regression analysis may be used to find a relation between Ui and the rate of glucose concentration change (e.g., using G(t) near ti) for a plurality of therapies provided during a therapy period.
  • the outcomes of one or more regression analysis may be used in the optimization process to determine a value of the control parameter.
  • the therapy data captured and stored during one or more therapy periods may be divided to equal time intervals wherein each time interval starts and ends at substantially the same specific start and end times within a 24 period.
  • an autoregression model may be derived for the glycemic control over the time interval between the specific start and end times. Subsequently, the resulting autoregression model may be used to determine whether the glycemic control has been improved compared to a previous therapy period. In some cases, the resulting autoregression model may be used to make additional adjustments to one or more control parameters in the subsequent therapy periods (after therapy periods following the period in which an autoregression model is determined).
  • the outcome of the statistical analysis of therapy data may be used to evaluate the accuracy glucose signal generated by a CGM sensor.
  • the glucose level control system may generate a control parameter optimization report that may include some or all of the statistical quantities calculated during the optimization process, outcomes of the statistical analysis and graphical representation of the therapy data and related risk assessments.
  • a Control Variability-Grid Analysis may be included in the control parameter optimization report, to visualize the variability of CGM data at a group level from a glucose-control point of view.
  • the graphs may comprise distinctive groups of graphs, for example, to visualize average glycemia and deviations from target values, visualize variability and risk assessment, and event-based clinical characteristics.
  • the graphical data may represent average glycemia and deviations from target glucose trace and aggregated glucose trace representing the time spent below, within or above the preset target range and visualizing the crossing of glycemic thresholds.
  • the control parameter optimization report may include graphs representing variability and risk assessment data. For example, a risk trace may be presented to highlighting essential variance (e.g., by equalizing the size of glucose deviations towards hypo- and hyperglycemia, emphasizing large glucose excursions, and suppress fluctuation within target range).
  • histogram of blood glucose rate of change may be included in the report to presented, for example, the spread and range of glucose transitions.
  • Poincare' plots may be included in the report to visualize the stability of the glucose signal during different therapy periods that may be also associated with different values of a control parameter.
  • An automated glucose level control system such as the glucose level control system 510, can adjust a subject’s glucose level over time by administering medicament, such as insulin or a counter-regulatory agent (e.g., glucagon). It is generally desirable that the glucose level be maintained within a setpoint range that is optimal for maintaining the subject’s health or controlling the subject’s disease (e.g., diabetes). Using one or more of the controllers 518, the glucose level control system 510 can adjust the subject’s glucose level to be within the desired glucose setpoint range. In certain embodiments, the control algorithm used by the one or more controllers 518 may adapt over time to control the subject’s glucose level more smoothly or such that there is less dynamic range in the subject’s glucose level.
  • medicament such as insulin or a counter-regulatory agent (e.g., glucagon). It is generally desirable that the glucose level be maintained within a setpoint range that is optimal for maintaining the subject’s health or controlling the subject’s disease (e.g., diabetes).
  • the control algorithm can be adapted over time so that the subject’s glucose level is maintained within a more consistent range. It is typically desirable to not only maintain the subject’s glucose level within a desired setpoint range, but to also limit fluctuations or large fluctuations in glucose level. It should be understood that some fluctuations may occur even in a completely healthy individual as meals and daily life (e.g., sleep, exercise, etc.) may affect glucose level of a subject. However, it is typically desirable to limit fluctuations of glucose level that go beyond that of a healthy or disease-free subject.
  • the ability of the glucose level control system 510 to adapt the control algorithm for administering medicament helps maintain the subject’s glucose level within the desired setpoint range.
  • glucose level control system 510 A number of control algorithms that can be implemented by the glucose level control system 510 described herein are described in the following patents that are hereby incorporated by reference herein in their entirety and made a part of this application: U.S. Patent No. 7,806,854, issued October 5, 2010; U.S. Patent No. 9,833,570, issued December 5, 2017; U.S. Patent No. 10,543,313, issued January 28, 2020; U.S. Patent No. 10,842,934, issued November 24, 2020; and U.S. Patent No. 10,940,267, issued March 9, 2021. It should be understood that the glucose level control system 510 may implement other control algorithms instead of or in addition to the control algorithms described in the aforementioned patents.
  • glucose level there are times when the amount of time to adapt a subject’s glucose level is less than ideal.
  • the control algorithms that control the administering of medicament may take longer to adapt for subjects with higher insulin per body mass or weight (e.g., per kg) requirements.
  • an adapted control algorithm is no longer applicable or well-adapted to the subject.
  • the glucose level of the subject may be less consistent and may include more fluctuations. For example, a subject whose body is going through significant physiological changes (e.g., puberty, large or rapid weight change, sickness, etc.) may result in larger glucose level fluctuations or for an adapted control algorithm to no longer be well -adapted to the subject.
  • unusual activity e.g., a heavy or significant exercise session for a subject that usually does not exercise
  • the control algorithm will adapt to the physiological changes or other causes of glucose level fluctuations in the subject.
  • glucose control may fluctuate more and/or maintenance of the subject’s disease may be suboptimal .
  • providing different operating modes for one or more of the glucose level controllers 518 that provide for different dosing modes and/or adaptation ranges for the glucose control algorithm of the ambulatory medical device 100 can reduce the time to adapt the control algorithm used to control administering of medicament to the subject.
  • the use of different operating modes that may be selected based on one or more physiological characteristics (e.g., weight, sex, age, sensitivity to insulin, sensitivity to glucose, etc.) of the subject can reduce the adaptation time of the control algorithm for certain subjects. Further, the use of different operating modes can reduce fluctuations in glucose level of the subject. Having different operating modes with different adaptation modes enables the glucose level control system to narrow or widen the adaptation range based on one or more characteristics of the subject, which may be determined by the ambulatory medical device 100, a healthcare provider, a subject, or other user.
  • adjusting the adaptation range may adjust the quantity of dosing, the timing of dosing, the frequency of dosing, or any other factor associated with the administering of medicament to the subject.
  • one operating mode may be a high dose mode that results in larger doses of medicament being administered with each bolus of medicament and/or within a particular time period compared to a normal or non high dose mode.
  • providing different operating modes for the glucose level controllers 518 may include providing different adaptation ranges and/or different levels of aggressiveness for adjusting one or more control parameters of a control algorithm that generates control signals for controlling the administration of medicament to the subject.
  • the operating mode may be adjusted from an operating mode associated with a particular adaptation range or aggressiveness to another operating mode associated with a different adaptation range or aggressiveness. For instance, if a physician or healthcare provider knows that a subject needs on average more insulin than a particular threshold, the ambulatory medical device may be configured (e.g., by the healthcare provider) to permit a user to adjust the mode of operation to limit or adjust the range of the aggressiveness control parameter (e.g., by eliminating half of the adaptation range).
  • the mode can be activated by interacting with a user interface element of the ambulatory medical device (e.g., by selecting a switch, pushing a button, interacting with a touch screen, causing a command to be transmitted to the ambulatory medical device from another electronic device, etc.).
  • a user interface element of the ambulatory medical device e.g., by selecting a switch, pushing a button, interacting with a touch screen, causing a command to be transmitted to the ambulatory medical device from another electronic device, etc.
  • statistical analysis of glycemic control can be used to determine whether a particular operating mode, such as a high dose mode is appropriate.
  • the ambulatory medical device may be able to monitor one or more control parameters and recommend high dose mode, or a non high dose mode, based at least in part on the adapted values for the one or more control parameters.
  • a subject or user may desire to invoke an operating mode (e.g., a high dose mode) for a subset of available controllers.
  • an operating mode e.g., a high dose mode
  • the subject or other user may desire to invoke a high dose mode for a model predictive controller (e.g., the corrective insulin controller 626) that controls correction boluses while maintaining a basal controller (e.g., the basal controller 624) and/or meal controller (e.g., the priming insulin controller 628) in a normal or non high dose mode.
  • the subject or user may separately set operating modes for each controller of the glucose level controllers 518.
  • the ambulatory medical device 100 may separately set the operating mode for each controller of the glucose level controllers 518.
  • one or more controllers that control administering correction doses, basal doses, and/or meal doses may individually or collectively be configured to operate in high dose mode or non high dose mode.
  • FIG. 19 presents a flowchart of an example dose mode transition process 1900 in accordance with certain embodiments.
  • the process 1900 can be implemented by any system that can operate using a plurality of operating modes that affect a control algorithm used by an ambulatory medical device to administer medicament to a subject.
  • the process 1900 in whole or in part, can be implemented by, for example, an ambulatory medical device 100, a glucose level control system 200, a glucose level control system 510, a controller 202, a controller 518, a processor 530, a glucagon controller 622, a basal controller 624, a corrective insulin controller 626 (e.g., a model predictive controller), a priming insulin controller 628 (e.g., a meal controller), a glucose sensor 516, or a glucose sensor interface that interfaces with the glucose sensor 516, among others.
  • a corrective insulin controller 626 e.g., a model predictive controller
  • a priming insulin controller 628 e.g., a meal controller
  • glucose sensor 516 e.g., a meal controller
  • any number of systems, in whole or in part can implement the process 1900, to simplify discussion, the process 1900 will be described with respect to particular systems.
  • the process may begin at block 1902 where, for example, the controller 518 receives a glucose level signal associated with a subject.
  • the glucose level signal may be received via a glucose sensor interface from a glucose sensor, such as a continuous glucose monitoring (CGM) sensor.
  • CGM continuous glucose monitoring
  • the glucose sensor may be attached to or otherwise in communication with a subject to obtain a glucose level reading or to measure a glucose level of the subject.
  • the block 1902 may include one or more of the embodiments described herein with respect to block 1302.
  • the ambulatory medical device 100 provides first therapy to the subject during a first therapy period based at least in part on the glucose level signal and a control algorithm operating in a first operating mode.
  • the control algorithm may include any type of algorithm used to generate a dose control signal that causes glucose control therapy to be provided to the subject.
  • the control algorithm may include a closed -loop algorithm that determines one or more boluses of insulin or other medicament that is to be provided to the subject to help manage the subject’s disease.
  • the control algorithm may be or may be based on the bi -exponential PK model described herein.
  • the block 1904 may include one or more of the embodiments described herein with respect to block 1304 or 1604.
  • the first therapy may be delivered based at least in part on a first value of a control parameter used by the control algorithm.
  • the control parameter may include any parameter that may affect the execution of the control algorithm and/or the generating of the dose control signal.
  • the control parameter may be associated with a quantity of medicament, an insulin concentration (e.g., U100, U200, U300, etc.), a delivery rate of medicament, a step- size or graduation used to modify the quantity of medicament between administrations of the medicament, a timing of supplying medicament to the subject, a rate of supplying medicament, a glucose absorption rate, a time until the concentration of insulin in blood plasma for a subject reaches half of the maximum concentration, a time until the concentration of insulin in blood plasma for a subject reaches a maximum concentration, or any other control parameter that can impact a timing or quantity of medicament (e.g., insulin or counter- regulatory agent) supplied or administered to a subject.
  • a timing or quantity of medicament e.g., insulin or counter- regulatory agent
  • the first value of the control parameter may be selected based on a first adaptation range.
  • the adaptation range may set or be associated with a universe of values for the control parameter.
  • the adaptation range may indicate boundary conditions for the control parameter.
  • the adaptation range may specify minimum and/or maximum values for the control parameter.
  • the adaptation range may specify a step-size, a graduation, or a granularity of values of the control parameter or between values of the control parameter.
  • the first adaptation range may include or may be an initial set of values for the control parameter.
  • This initial set of values may be a set of default values associated with the ambulatory medical device 100, an initial set of values determined by a healthcare provider, an initial set of values determined based on clinical data for the subject or patients that share physiological and/or demographic characteristics with the subject, a set of values determined by an adaptive control algorithm used by the ambulatory medical device 100, or any other set of values that may be associated with or designated as part of the first adaptation range.
  • the value of the control parameter may change from the initial set of values over time based at least in part on an adaptive control algorithm, the adaptation range, and/or physiological measurements (e.g., glucose level measurements) of the subject.
  • the different operating modes of the ambulatory medical device 100 and/or of the control algorithm may result in different doses of medicament.
  • at least one of the operating modes may be termed a “high dose mode” or “high dose operating mode” in that the doses of medicament administered in high dose mode may be generally higher or higher on average than one or more other operating modes that may be termed a “normal mode,” “normal operating mode,” a “non high dose mode,” or a “non high dose operating mode.”
  • a high dose operating mode may supply a higher total daily dose (TDD) of insulin (e.g., 80, 100, or 120 units of insulin) than a normal or non high dose operating mode (e.g., 40, 50, or 60 units of insulin).
  • TDD total daily dose
  • a high dose operating mode may use an adaptation range of control parameter values (e.g., an aggressiveness factor from 5 to 10) that differs from an adaptation range of the control parameter values in a normal or non high dose operating mode (e.g., an aggressiveness factor from 1 to 10).
  • a normal or non high dose operating mode e.g., an aggressiveness factor from 1 to 10.
  • normal mode or normal operating mode is used herein to distinguish from high dose mode, it should be understood that the term normal operating mode is not intended to be limiting, but is instead used to differentiate between an operating mode configured to operate using a first adaptation range or set of parameters and an operating mode (e.g., high dose mode) configured to operate using a second adaptation range or set of parameters that provides or on average provides a greater amount of medicament within a particular time period.
  • the high dose operating mode may provide a greater amount of medicament within the particular time period compared to the normal dose operating mode, in some cases, the medicament provided over another time period, which may include in part or in total the particular time period, may be the same in both high dose operating mode and normal dose operating mode.
  • the first operating mode may be a default, normal, or non high dose operating mode.
  • the first operating mode may be the high dose operating mode.
  • the first operating mode may be the high dose operating mode.
  • the prior example indicates that high dose mode may result in a higher TDD compared to a non high dose mode, it should be understood that the present disclosure is not limited as such.
  • high dose mode may result in some or all doses of medicament being higher than in non high dose mode, but the TDD may or may not be higher.
  • the glucose level control system 510 of the ambulatory medical device 100 receives an indication to operate the control algorithm in a second operating mode that is associated with a different adaptation range than the first operating mode.
  • the second operating mode may be a high dose operating mode as described herein.
  • the second operating mode may be a normal or non high dose operating mode.
  • the indication to operate the control algorithm in the second operating mode may be received in response to a user interacting with a user interface.
  • a user may select an operating mode from a user interface of the ambulatory medical device 100 or an electronic device (e.g., a computer, a dedicated controller, a smartphone, a smartwatch, etc.) is communication with the ambulatory medical device 100.
  • an electronic device e.g., a computer, a dedicated controller, a smartphone, a smartwatch, etc.
  • the second operating mode may be associated with providing more aggressive treatment of the subject than the first operating mode.
  • Providing more aggressive treatment may include providing larger amounts of medicament for each dose and/or providing doses more frequently.
  • providing more aggressive treatment may include administering the medicament more quickly compared to less aggressive treatment.
  • switching operating modes to adjust the aggressiveness of treatment may include one or more of the embodiments for adjusting the aggressiveness of a controller, such as the glucose level control system 510, described in U.S. Patent No. 7,806,854 issued on October 5, 2010, which is hereby incorporated by reference in its entirety and made a part of this specification.
  • the process 1900 may be fully automated.
  • the indication to operate the control algorithm in the second operating mode may be determined automatically instead of from a user input.
  • the glucose level control system 510 may determine to switch the control algorithm from the first operating mode to the second operating mode based at least in part on one or more effects of the first therapy provided at the block 1904. For example, if it is determined from a glucose level signal that the glucose level of the subject is higher than expected after an instantaneous administering of therapy and/or after administering therapy over time, the glucose level control system 510 may modify the operating mode from a first operating mode associated with a first adaptation range to a second operating mode associated with a second adaptation range.
  • the operating mode of the ambulatory medical device 100 can be dangerous, it is often the case that the user is a healthcare provider. However, it is possible for other users to modify the operating mode of the ambulatory medical device 100.
  • the user may be the subject, a parent or guardian of the subject, a healthcare provider, etc.
  • the competence or ability of the user to safely modify operation of the ambulatory medical device 100 may be determined before permitting modification of the operating mode of the ambulatory medical device 100. For example, a user may be required to undergo training or pass a test before being permitted to change operating modes of the ambulatory medical device.
  • the glucose level control system 510 switches operation of the control algorithm from the first operating mode to the second operating mode.
  • Switching operation of the control algorithm may include switching the adaptation range from the first adaptation range (e.g., a non high dose adaptation range) to a second adaptation range (e.g., a high dose adaptation range).
  • the block 1908 may include switching the control algorithm from a first control algorithm associated with the first adaptation range to a second control algorithm associated with the second adaptation range.
  • the block 1908 may include switching a control parameter used by the control algorithm from a first set of one or more values associated with the first adaptation range to a second set of one or more values associated with a second adaptation range.
  • the first adaptation range may be a first initial value for a control parameter.
  • the control parameter may change from the first initial value and/or be adapted over time.
  • the second adaptation range may be a second initial value for the control parameter.
  • the control parameter may change from the second initial value and/or be adapted over time.
  • the second adaptation range may result in a higher medicament response than the first adaptation range (or relative to a default adaptation range) over time during a glucose response period occurring in response to and/or after a glucose level signal (e.g., the glucose level signal received at the block 1902) indicates a glucose excursion in the subject.
  • a glucose level signal e.g., the glucose level signal received at the block 1902
  • the higher medicament response can encompass different initial settings and/or a different adaptation range for settings relative to a default or non high dose control algorithm setting or operating mode.
  • the higher medicament response may correspond to a larger amount of medicament being supplied over the glucose response period with the second operating mode than the first operating mode.
  • the glucose response period may be any time period that is at least long enough to determine a change in glucose level responsive to the administering of medicament (e.g., insulin or counter -regulatory agent).
  • medicament e.g., insulin or counter -regulatory agent
  • the glucose response period may be on the order of minutes, thirty minutes, less than thirty minutes, one hour or less, etc.
  • the glucose response period may vary based on the type of insulin or medicament.
  • the glucose response period may be a subset of a total glucose response period associated with the glucose level signal indicating the glucose excursion in the subject.
  • a higher medicament response may include a larger bolus of medicament, a more aggressive administration of medicament, more frequent administration of medicament, or any other modification in the administration of medicament that results in a speedier modification to glucose level compared to the medicament response associated with the first adaptation range.
  • the higher medicament response can encompass different initial settings and/or a different adaptation range for one or more control parameters relative to the default control parameter settings.
  • the second adaptation range may be a subset of the first adaptation range.
  • the first adaptation range may encompass a set of values between a minimum and a maximum
  • the second adaptation range may encompass a set of values between a midpoint of the first adaptation range and the maximum of the first adaptation range.
  • the second adaptation range may partially overlap the first adaptation range.
  • the second adaptation range may encompass a set of values between a value within the first adaptation range and a value that exceeds a maximum value of the first adaptation range or that is below a minimum value of the first adaptation range.
  • the first and second adaptation ranges have the same minimum and maximum values, but may have a different set of values or number of values between the minimum and maximum values.
  • the first adaptation range may include twenty discrete values evenly spaced between the minimum and maximum values, while the second adaptation range may have ten values evenly spaced between the minimum and maximum values. Accordingly, in some cases, a step size or delta between two successive values in the second adaptation range may be larger than between two successive values in the first adaptation range.
  • the step size may vary among different portions of the adaptation range. For example, the step size may increase between successive values heading from the minimum value towards the maximum value of the adaptation range. Further, the step size may be consistent in one adaptation range, but may vary in another adaptation range.
  • the breadth of values in the second adaptation range may be less than the breadth of values in the first adaptation range.
  • the delta between the minimum and maximum value in the second adaptation range may be less than the delta between the minimum and maximum value in the first adaptation range.
  • the delta between the minimum and maximum values in the first and second adaptation ranges may be the same.
  • the delta between successive values in the first adaptation range may be lesser, greater, or equal to the delta between successive values in the second adaptation range.
  • the adaptation ranges may be continuous. In such cases, the delta between values in the adaptation ranges may be zero.
  • one adaptation range may be continuous while another adaptation range may not be continuous within or between the range of values constituting the adaptation range.
  • control parameter can be any parameter that may be used by the control algorithm to control or modify the administering of medicament.
  • the control parameter may affect the timing, frequency, or size of medicament (e.g., insulin or glucagon) dosing.
  • the control parameter and/or the control algorithm may relate to the administering of a basal insulin dose.
  • the lowest bound of the basal rate may be set at the midpoint of the range of the basal rate when operating in the normal dose mode.
  • the adaptation rate may be maintained the same between the operating modes, but the change in the minimum and/or maximum basal rates may affect the amount of time to reach the maximum basal rate effectively changing the aggressiveness of the treatment or therapy.
  • the adaptation rate may be modified between operating modes.
  • the adaptation ranges may relate to or correspond to a multiple of a nominal basal rate.
  • a nominal basal rate For instance, suppose that the baseline units per hour of a basal dose is related to the body mass of the subject in kg/100. In other words, one unit of insulin may be administered for each 100 kg of mass of the subject. In high dose mode, the baseline of insulin may be 50% more than in normal mode. Further, in one non-limiting example, the nominal basal rate can be adapted from 0.33 - 3.0 times the baseline (e.g., the first adaptation range) when the control algorithm is operating in normal mode.
  • the nominal basal rate when in high dose mode, can be adapted from 1.0 - 3.0 times the baseline (e.g., the second adaptation range). As another example, the nominal rate can be adapted from 1.0 - 5.0+ times the baseline when in high dose mode or in an ultra high dose mode (e.g., as a third adaptation range). In other words, in some cases, the nominal rate may be biased higher in high dose mode compared to non high dose mode. In some cases, the different operating modes may affect nominal basal calculations, but may not affect instantaneous basal calculations.
  • control parameter and/or control parameter may relate to administering of a correction insulin dose.
  • a minimum correction dose size identified in a high dose mode e.g., as part of the second adaptation range
  • a minimum correction dose size identified in a normal dose mode e.g., as part of the first adaptation range.
  • an aggressiveness of the adaptation range may be set higher for high dose mode than normal dose mode while maintaining adaptation rate.
  • the adaptation rate may be modified for one operating mode versus another operating mode.
  • the correction dose may relate to a baseline value.
  • the baseline total daily dose (TDD) may be 0.5 u/kg/day.
  • the baseline TDD may be 0.75, 1, or 1.5 u/kg/day.
  • an aggressiveness factor can fluctuate from 5-10 with the lower value being more aggressive.
  • the corrective insulin controller 626, or MPC controller may determine an aggressiveness factor that provides optimum glycemic control.
  • the aggressiveness factor can fluctuate from 5-7.5, removing half of the least aggressive portion of the range.
  • the aggressiveness of the MPC controller may be increased by removing the lower aggressiveness values.
  • the aggressiveness may refer to how quickly and/or how forcefully the controller reacts to instantaneous readings of glucose level. How forcefully the controller reacts to the instantaneous readings of glucose level may relate to the dose size of medicament supplied to the subject.
  • the medicament supplied may be a combination of nominal basal (e.g., controlled by the nominal rate controller 630) and instantaneous basal (e.g., controlled by the modulating controller 632).
  • the nominal basal rate may be a basal rate set based on a resting or fasting insulin requirement for the subject.
  • switching operating modes switches how quickly the control algorithm adapts to different glucose levels, or how quickly the basal rate is scaled from the normal value.
  • the instantaneous basal value may be the insulin required based on a level of activity for the subject, hormones, stress, etc.
  • the instantaneous basal may change over time based on the glucose levels of the user and may be associated with an aggression factor.
  • the basal controller 624 may set the range of the instantaneous basal centered around the nominal basal rate based on an aggressiveness factor.
  • the low instantaneous basal may be at or around 0 with a max range based on aggressiveness (e.g., low aggressiveness might be 2-3x nominal, and high aggressiveness could be up to lOx).
  • the size of the adaptation range for the instantaneous basal may depend on aggressiveness and/or the adaptation rate.
  • control parameter and/or control parameter may relate to administering of a meal dose of medicament.
  • a meal dose size for a particular size meal may be larger for a high dose mode adaptation range than for a normal (or low) dose mode adaptation range.
  • a greater bolus of medicament may be administered in high dose mode than in normal dose mode.
  • the baseline dose may be 0.05 u/kg for a particular size meal.
  • the baseline may be 0.1, 0.15, 0.2, or 0.3 u/kg.
  • an initial dose of medicament administered in high dose mode may be higher than an initial dose of medicament in normal dose mode for a particular scheduled or identified meal of a particular identified size.
  • the subsequent adaptation process that adapts the control algorithm may be the same in both modes.
  • the adaptation process may adjust the size and distribution of insulin doses for different meals and/or different size meals for a subject. Methods for adapting meal doses that may be used with embodiments of the present disclosure are described in U.S. Patent No. 9,833,570 issued on December 5, 2017, which is hereby incorporated by reference herein in its entirety and made a part of this application.
  • the meal controller had already adapted the control algorithm to the subject, switching from normal operating mode to high dose operating mode may not result in a change to the meal dose of insulin.
  • a control algorithm adapted specifically to a user would not change as the control algorithm has already determined the optimal dose for a subject based on a reported meal type and/or size.
  • an initial dose of medicament in high dose mode for a reported meal may be higher than in normal dose mode.
  • the total quantity of medicament delivered over a time period comprising multiple administrations of medicament is the same whether the control algorithm is operating in the first operating mode or the second operating mode.
  • the rate at which the medicament is delivered may differ. For example, in the normal operating mode, more doses of medicament may be delivered over time, but with a lower quantity compared to high dose mode, which may have less doses of medicament, but with each dose being a greater amount of medicament.
  • the change in glucose level may be slower with normal operating mode than with high dose operating mode.
  • the total amount of medicament delivered over a time period may differ.
  • the amount of medicament delivered may be higher or the same in high dose mode with achieving a lower mean glucose level for the subject over a particular time period.
  • the ambulatory medical device 100 provides second therapy to the subject during a second therapy period using the control algorithm operating in the second operating mode.
  • This second therapy period may be any period of time after the control algorithm is switched from a first operating mode to a second operating mode at the block 1908.
  • the second therapy may be delivered based at least in part on a second value of the control parameter used by the control algorithm.
  • the second value is selected from the second adaptation range.
  • an initial value for the control parameter in the first operating mode may be the same as an initial value for the control parameter in the second operating mode.
  • the value of the control parameter may vary over time or may vary differently over time when operating in the second operating mode than when operating in the first operating mode.
  • the initial value in the first operating mode and the initial value in the second operating mode may differ.
  • the initial value in each operating mode may be a default value for the control parameter in the respective operating mode.
  • the value of the control parameter may change overtime in accordance with the control algorithm and/or adaptation range associated with the operating mode.
  • process 1900 has been described with respect to two operating modes, for example, a high dose operating mode and a normal or non high dose operating mode, it should be understood that the present disclosure is not limited as such.
  • the ambulatory medical device 100 may support more than two operating modes. There may be three, four, or more operating modes. Each operating mode may be associated with different initial values for a control parameter and/or different adaptation ranges. Further, in some cases, some of the operating modes may be associated with different values and/or adaptation ranges for different control parameters. For example, while a first set of operating modes may relate to different values and/or adaptation ranges corresponding to bolus sizes or dosage sizes, another set of operating modes may relate to different values and/or adaptation ranges corresponding to the timing of or frequency of medicament doses.
  • the blocks 1902 and 1904 may be optional or omitted.
  • the ambulatory medical device 100 may be configured to initially operate in the high dose operating mode. This may occur, for instance, when a health care provider determines that a subject should begin treatment using high dose mode because, for example, the subject is first diagnosed with diabetes as a teenager or has some other physiological characteristic that corresponds to likely requiring treatment using high dose mode instead of non high dose or normal operating mode.
  • the first operating mode may be a high dose mode and the second operating mode may be a normal operating mode.
  • operations associated with the block 1904 may be performed using an adaptation range associated with high dose mode and the block 1908 may switch the control algorithm from the high dose mode to a normal dose mode associated with a different adaptation range than the high dose mode.
  • the block 1908 may switch the control algorithm from the high dose mode to a higher dose mode (e.g., ultra high dose mode) associated with an adaptation range or set of parameters that provides or on average provides a greater amount of medicament within a particular time period than the high dose mode and the normal operating mode.
  • a higher dose mode e.g., ultra high dose mode
  • control algorithm may adapt over time to the subject based on the glucose levels of the subject over time as determined from the glucose level signal.
  • adaptation of the control algorithm may include automatically switching or initiating dosing modes and/or adaptation ranges from one to another.
  • the process 1900 has been described with respect to a normal operating mode and a high dose operating mode, it should be understood that other operating modes are possible.
  • the first operating mode may be an operating mode that is biased towards a lower or safe operating mode.
  • the lower or safe operating mode may be associated with an adaptation range that provides less medicament throughout the adaptation range and/or adjusts the medicament dosage using smaller adjustments as the control algorithm is adapted over time compared to a normal operating mode.
  • risks relating to over medicating are reduced. For example, the risk of hypoglycemia due to excess delivery of insulin may be reduced.
  • the operating mode associated with the reduced or lower adaptation range may be termed a “timid operating mode.”
  • a “timid” operating mode may be desirable for a subject who is particularly susceptible to insulin and/or has a lower tolerance to the effects of hypoglycemia. Further, a “timid” operating mode may be desirable for a subject who is going through physiological changes that may affect disease management.
  • a glucose level signal is received at the block 1902. It should be understood that the glucose level signal may be received continuously, periodically, intermittently, in response to a command, or on any other schedule throughout the process 1900. Moreover, the glucose level signal may vary over time indicating corresponding to the changing glucose levels of the subject. Thus, the administering of the first therapy at the block 1904 and the second therapy at the block 1910 may be based at least in part on the glucose level signal received throughout the process 1900.
  • the process 1900 is with respect to insulin dosing, it should be understood that embodiments disclosed herein may be applicable to other forms of medicament.
  • the process 1900 can be used with respect to the administering of counter-regulatory agent, such as glucagon.
  • the operating modes may affect the administering of insulin, counter -regulatory agent, or both insulin and counter-regulatory agent.
  • the medicament may include any other type of medicament that may be administered by an automated medical device including medicament for managing diabetes and medicament for managing other disease.
  • a greater amount of medicament may be administered with operating in a high dose mode compared to a normal or non high dose mode.
  • the total quantity of medicament delivered over a time period (e.g., a half day, a day, a week, etc.) comprising multiple administrations of medicament may be the same or on average the same whether the control algorithm is operating in the first operating mode or the second operating mode.
  • doses of medicament may sometimes be larger when operating in high dose mode, the number of administrations of medicament may be less because, for example, the subject more quickly reaches a target setpoint.
  • the TDD or a total amount of medicament administered on average over a particular time period may be the same.
  • the total amount of medicament delivered over a time period may, at least on average, be greater in a high dose mode than a normal dose mode.
  • the average glucose level may be lower despite the larger doses due, for example, to a change in frequency of the dosing of medicament (e.g., insulin and/or counter -regulatory agent).
  • the ambulatory medical device 100 may receive an indication to operate the control algorithm in a higher medicament dose mode as the initial mode.
  • the first operating mode is the high dose mode and the control algorithm operates in the higher medicament response mode as the initial mode.
  • the higher medicament response mode may be associated with higher medicament response settings relative to a default operating mode or a non high dose operating mode. Further, higher medicament response settings may include one or more of an initial settings, or an adaptation range that results in a higher medicament response within a glucose response period than the default or non high dose mode.
  • FIG. 20 presents a flowchart of an example automated dose mode transition process 2000 in accordance with certain embodiments.
  • the process 2000 can be implemented by any system that can automatically switch or transition a control algorithm used by an ambulatory medical device to administer medicament to a subject from a first operating mode to a second operating mode, or vice versa.
  • the process 2000 in whole or in part, can be implemented by, for example, an ambulatory medical device 100, a glucose level control system 200, a glucose level control system 510, a controller 202, a controller 518, a processor 530, a glucagon controller 622, a basal controller 624, a corrective insulin controller 626 (e.g., a model predictive controller), a priming insulin controller 628 (e.g., a meal controller), a glucose sensor 516, or a glucose sensor interface that interfaces with the glucose sensor 516, among others.
  • a corrective insulin controller 626 e.g., a model predictive controller
  • a priming insulin controller 628 e.g., a meal controller
  • the process may begin at block 2002 where, for example, the ambulatory medical device 100 provides first therapy to the subject during a first therapy period based at least in part on a control algorithm operating in a first operating mode.
  • the block 2002 may include one or more of the embodiments described herein with respect to the block 1904.
  • the therapy may be provided in response to and/or based at least in part on a glucose level signal received at a glucose sensor interface from a glucose sensor in communication with the subject.
  • the block 2002 may include one or more of the embodiments described with respect to the block 1902.
  • the glucose level control system 510 determines a first effect of the first therapy. Determining the first effect of the first therapy may include receiving a glucose level signal corresponding to a glucose level of a subject. Further, determining the first effect of the first therapy may include determining an effect of a medicament (e.g., insulin) supplied to the subject during the first therapy period on the subject or on the glucose level of the subject.
  • the block 2004 may include one or more of the embodiments described herein with respect to the block 1306 or 1806.
  • the processor 530 switches the control algorithm to a second operating mode.
  • the block 2006 may include one or more of the embodiments described herein with respect to the block 1908.
  • the control algorithm is switched in response to a user command or an interaction with a user interface by a user.
  • the control algorithm is switched automatically in response to a trigger, such as an elapsing of time, a schedule, a glucose level signal satisfying a threshold, or any other automated trigger.
  • the ambulatory medical device 100 provides second therapy to the subject during a second therapy period based at least in part on the control algorithm operating in the second operating mode.
  • the block 2008 may include one or more of the embodiments described herein with respect to the block 1910.
  • the glucose level control system 510, or the processor 530 thereof determines a second effect of the second therapy. Determining the second effect of the second therapy may include receiving a glucose level signal corresponding to a glucose level of a subject. Further, determining the second effect of the second therapy may include determining an effect of a medicament (e.g., insulin) supplied to the subject during the second therapy period on the subject or on the glucose level of the subject.
  • the block 2010 may include one or more of the embodiments described herein with respect to the block 1314 or 1812.
  • the glucose level control system 510, or the processor 530 thereof compares the second effect with the first effect.
  • the statistical comparison may include one or more of the processes described in U.S. Publication No. 2021/0016004 published on January 21, 2021, which is hereby incorporated by reference herein in its entirety and made a part of this specification.
  • the block 2012 may include one or more of the embodiments described with respect to the block 1316 or 1814.
  • the glucose level control system 510 determines whether the comparison performed at the block 2012 indicates that the control algorithm should operate in the first operating mode or continue operating in the second operating mode. Determining whether the comparison indicates that the control algorithm should operate in the first operating mode or continue operating in the second operating mode may be based on a determination of which operating mode better manages the subject’s disease. The determining of which operating mode better manages the subject’s disease may include determining which operating mode maintains the subject’s glucose level within the target setpoint for a longer period of time or at a higher rate within a particular time period.
  • determining which operating mode better manages the subject’s disease may include determining which operating mode is associated with a more stable (e.g., having less fluctuations) glucose level.
  • the decision block 2014 may include one or more of the embodiments associated with the block 1316 and/or the decision blocks 1816, 1818.
  • the ambulatory medical device 100 continues to provide therapy to the subject using the control algorithm operating in the second operating mode at block 2016.
  • the process 2000 may end at this point.
  • the process 2000 may return to the block 2010 to determine updated second effect data and to repeat portions of the process 2000 to determine whether to modify the operating mode of the control algorithm.
  • the glucose level control system 510 or the processor 530 thereof, automatically switches the control algorithm from the second operating mode to the first operating mode at the block 2018.
  • Automatically switching the control algorithm may include switching the control algorithm in response to a trigger and/or without the user interacting with a user interface.
  • the result of the comparison performed at the block 2012 may serve as a trigger to switch operating modes of the control algorithm.
  • Switching operating modes of the control algorithm may include switching control parameter values and/or switching adaptation ranges for a control parameter of the control algorithm.
  • the block 2018 can include one or more of the embodiments described with respect to the block 2006 and/or the block 1908.
  • the ambulatory medical device 100 provides third therapy to the subject during a third therapy period based at least in part on the control algorithm operating in the first operating mode.
  • the block 2020 may include one or more of the embodiments described herein with respect to the block 2002.
  • the process 2000 has been described with respect to two operating modes, for example, a high dose operating mode and a normal or non high dose operating mode, it should be understood that the present disclosure is not limited as such and that more than two operating modes may exist that may each be associated with different values, initial values, adaptation ranges, control parameters, etc. Further, one or more of the embodiments described with respect to the number of operating modes supported by the process 1900 may be applicable to the process 2000.
  • the block 2018 may include switching the control algorithm from the second operating mode to a third operating mode that differs from both the first operating mode and the second operating mode. The determination of which operating mode to switching the control algorithm may be based at least in part on the comparison performed at the block 2012.
  • the first operating mode may be a high dose mode or a non high dose mode and conversely, the second operating mode may be a non high dose mode or a high dose mode.
  • both the first operating mode and the second operating mode may be high dose modes with one of the operating modes being a higher dose mode (e.g., an ultra high dose mode) than the other operating mode.
  • the process 2000 is described as using a comparison between the first effect and the second effect as a trigger for determining whether to change the operating mode of a control algorithm, the present disclosure is not limited as such.
  • Other triggers may be used to determine whether to modify the operating mode of the control algorithm and, in some such cases, the block 2012 may be omitted or may perform alternative processes.
  • the glucose level control system 510 may determine whether an autonomously generated value for the control parameter is within a portion of the first adaptation range that is not part of the second adaptation range. If the value is within the first adaptation range and not the second adaptation range, the operating mode may be associated with the first adaptation range may be maintained.
  • the operating mode may be switched to the second operating mode associated with the second adaptation range. Or if it is determined that the value is within the second adaptation range and not the first adaptation range, the operating mode may be switched to the second operating mode associated with the second adaptation range.
  • a determination of whether to switch operating modes may be based on the effect of the first therapy performed using a first operating mode without performing therapy using a second operating mode. For example, a set of one or more effects of one or more instances of therapy performed in the first operating mode may be determined and/or analyzed to determine whether to switch operating modes. In some cases, a set of effects measured for a set of instances of therapy may be analyzed to determine whether a subject’s health is being maintained or is being improved at a desired rate. For instance, the set of effects may be analyzed to determine whether a glucose level of the subject is moving towards a target setpoint at a desired rate when the control algorithm is operating in the first operating mode. If it is determined that the glucose level is not being adjusted at a desired rate, the control algorithm may be switched to the second operating mode.
  • the process 2000 may be used to determine when to switch to high dose mode. Further, the process 2000 may be used to determine when high dose mode is no longer applicable. For example, in some cases, teenagers may require higher doses of insulin and thus, it may be desirable to operate the ambulatory medical device in high dose mode for a teenager. However, when the teenager reaches adulthood, the insulin requirements may drop in some cases. In some such cases, the process 2000 may be used to revert to normal operating mode or non high dose operating mode. Second Example Automated Dose Mode Transition Process
  • FIG. 21 presents a flowchart of a second example automated dose mode transition process 2100 in accordance with certain embodiments.
  • the process 2100 can be implemented by any system that can automatically switch or transition a control algorithm used by an ambulatory medical device to administer medicament to a subject from a first operating mode to a second operating mode, or vice versa.
  • the process 2100 in whole or in part, can be implemented by, for example, an ambulatory medical device 100, a glucose level control system 200, a glucose level control system 510, a controller 202, a controller 518, a processor 530, a glucagon controller 622, a basal controller 624, a corrective insulin controller 626 (e.g., a model predictive controller), a priming insulin controller 628 (e.g., a meal controller), a glucose sensor 516, or a glucose sensor interface that interfaces with the glucose sensor 516, among others.
  • a corrective insulin controller 626 e.g., a model predictive controller
  • a priming insulin controller 628 e.g., a meal controller
  • glucose sensor 516 e.g., a meal controller
  • any number of systems, in whole or in part can implement the process 2100, to simplify discussion, the process 2100 will be described with respect to particular systems. Further, it should be understood that the process 2100 may include one or more of
  • the process may begin at block 2102 where, for example, the ambulatory medical device 100 provides first therapy to the subject during a first therapy period based at least in part on a control algorithm operating in a first operating mode.
  • the first operating mode may be selected by a user or determined automatically based on clinical data and/or physiological data measured by one or more sensors (e.g., a glucose sensor) in communication with or connected to the subject.
  • the block 2102 may include one or more of the embodiments described herein with respect to the blocks 1904 and/or 2002.
  • the glucose level control system 510 determines that an autonomously generated value of a control parameter used by the control algorithm is not associated with the first operating mode and/or is associated with a second operating mode.
  • the block 2104 includes determining that the autonomously generated value of the control parameter is within an adaptation range of the second operating mode and/or is not within an adaptation range of the first operating mode.
  • the autonomously generated value may be within the adaptation range of both operating modes.
  • the adaptation range of the second operating mode may be a subset of the adaptation range of the first operating mode.
  • a determination that the autonomously generated value is within the adaptation range of both operating modes may indicate not to switch operating modes or may indicate to maintain or switch to a particular operating mode. For instance if the glucose level control system 510 is operating in a high dose mode and the high dose mode is associated with an adaptation range that is a subset of an adaptation range of the non high dose mode, a determination that the autonomously generated value is within the adaptation range of the high dose mode (and also within the adaptation range of the non high dose mode) may indicate that the operating mode is to be maintained as the high dose mode.
  • the operating mode may be maintained in the non high dose mode regardless of whether the autonomously generated value is within the adaptation range of the high dose mode as it is also within the adaptation range of the non high dose mode.
  • the block 2104 includes determining that the autonomously generated value of the control parameter generates or causes an effect that is associated with the second operating mode. Moreover, in some cases, the block 2104 may include determining that the autonomously generated value of the control parameter generates or causes an effect that is not associated with the first operating mode.
  • the glucose level control system 510 or the processor 530 thereof, automatically switches the control algorithm to the second operating mode responsive, at least in part, to the determination at the block 2104.
  • the block 2106 may include automatically switching from a high dose mode to a non high dose more or to a higher dose mode.
  • the block 2106 may include automatically switching from a non high dose mode to a high dose mode.
  • the block 2106 may include one or more of the embodiments described with respect to the block 2018.
  • the ambulatory medical device 100 provides second therapy to the subject during a second therapy period based at least in part on the control algorithm operating in the second operating mode.
  • the block 2108 may include one or more of the embodiments described herein with respect to the blocks 1910 and/or 2008.
  • the process 2100 may be used to determine when to switch to high dose mode. Further, the process 2100 may be used to determine when high dose mode is no longer applicable. For example, in some cases, teenagers may require higher doses of insulin and thus, it may be desirable to operate the ambulatory medical device in high dose mode for a teenager. However, when the teenager reaches adulthood, the insulin requirements may drop in some cases.
  • the process 2100 may be used to revert to normal operating mode or non high dose operating mode. Further, as with the process 1900, the processes 2000 and 2100 may be used with insulin, glucagon, or any other type of medicament that may be used to control or manage diabetes. Moreover, in some cases, the processes disclosed herein may be used with other medicament used to control or manage other diseases. Additional Embodiments
  • the operating mode (e.g., high dose mode) of an ambulatory medical device or a control algorithm thereof may be set automatically based on a glucose level response to therapy.
  • the operating mode of the ambulatory medical device or control algorithm may be set manually.
  • the operating mode may be set using a button in an advanced options screen or by interacting with any other type of user interface.
  • the operating mode may be accessed at any time to turn on or off a particular operating mode.
  • the operating mode may be activated for a scheduled period of time. For example, the high dose operating mode may be activated for a week or for daytime hours. After the scheduled period of time, the operating mode may be switched back to another operating mode. Continuing the previous example, the operating mode may revert to a normal operating mode after the week or during nighttime hours.
  • an algorithm parameter may be switched from one value to another value when operating modes are switched.
  • an interface parameter may be switched from one value to another to indicate the operating mode or to activate a particular operating mode.
  • the control algorithm interface may be set to ‘O’ by default to indicate normal operating mode and may be switched to ‘G to indicate high dose mode.
  • the operating mode may modify different controllers, portions of the control algorithm, and/or aspects of medicament delivery.
  • the operating mode may modify one or more of basal delivery, model predictive controller (MPC) insulin or correction doses, and/or meal doses.
  • MPC model predictive controller
  • the basal controller may use an adjusted adaptation range when operating in the high dose mode such that the lowest bound or minimum value is set higher than the lowest bound of the normal operating mode (e.g., halfway of the normal operating mode range).
  • the adaptation range may be smaller in the high dose operating mode and, assuming the adaptation rate is maintained between operating modes, the time to reach the maximum value may be shortened.
  • the model predictive controller, or correction insulin controller may have an aggressiveness factor that corresponds at least in part to a timing or dose size of medicament supplied to the subject based at least in part on a glucose level of the subject.
  • the high dose operating mode may have the aggressiveness of the control algorithm set higher than the aggressiveness of the normal operating mode (e.g., set halfway within the adaptation range of the normal operating mode).
  • the adaptation range may be smaller in the high dose operating mode and, assuming the adaptation rate is maintained between operating modes, the time to reach the maximum value may be shortened.
  • the meal controller or the priming insulin controller, assuming not yet adapted to a specific subject, may have a particular dosing ratio (e.g., 0.1 u/kg) for a subject.
  • a subject in normal operating mode, a subject may receive 0.1 units of medicament for each kilogram the subject weighs in response to a meal announcement for a normal size meal.
  • different ratios of medicament may be supplied for different size meals or types of meals.
  • the ratio of medicament per kg supplied during a meal announcement may be a multiple (e.g., 1.5x, 2x, 3x, etc.) of the ratio supplied in normal dose operating mode.
  • different baselines can be used for different controllers or portions of the control algorithm. For example, different baselines for the meal controller may be used based on the insulin concentration used. If the ambulatory medical device is using U200 instead of U100, the meal controller may apply a lower ratio of insulin/kg for each meal (e.g., 0.05 u/kg). Further, in some cases, the ambulatory medical device recommends a type of insulin and/or an operating mode based on the different types or concentrations of insulin available (e.g., switch from U-100 to U-200). In certain embodiments, the ambulatory medical device may have multiple concentrations of insulin available. For instance, the ambulatory medical device may have a U100 and a U200 cartridge of insulin available. In some such cases, the ambulatory medical device can recommend a particular concentration of medicament based on the glucose level and rate of adaptation of the control algorithm for the subject.
  • Embodiments disclosed herein may be used with type 1 diabetics and type 2 diabetics.
  • the high dose mode may be turned on or off or may be used in part.
  • the high dose mode may be alternated with normal operating mode to help a subject each into or out of high dose mode.
  • different operating modes may be associated with different types of medicament or different concentrations of insulin.
  • normal operating mode may use U100 insulin and high dose operating mode may use U200 insulin.
  • the ambulatory medical device may support higher dose operating modes that provide higher dosing on average than the high dose operating mode.
  • an ultra-high dose operating mode that is associated with an adaptation range or an adaptation rate that provides more medicament or medicament at a faster rate than the high dose operating mode.
  • the ultra-high dose mode may have even more aggressive baselines and adaptation ranges than the high dose mode, which may have more aggressive baselines and adaptation ranges than normal dose mode.
  • the aggressiveness of the operating mode may change how quickly and how forcefully (e.g., the amount of insulin administered) the controller reacts to instantaneous readings of glucose level.
  • the range of parameters available to the control algorithm may be increased, and the controller can adapt accordingly.
  • Embodiments of the present disclosure may be tested with subj ects that generally use an above average total daily dose of insulin.
  • the systems disclosed herein may be tested with adolescents that on average received a TDD of 0.75 u/kg of insulin.
  • Tests may include operating the ambulatory medical device in normal operating mode for a time period (e.g., one week, two weeks, etc.) and then operating the ambulatory medical device in high dose operating mode for a time period (e.g., one week, two weeks, etc.).
  • Various glucose maintenance characteristics may be compared to determine which mode provides better maintenance of the subjects’ disease.
  • the average glucose level, the amount of fluctuations in glucose level, the frequency of hypoglycemic/hyperglycemic risk events, etc. can be compared to determine the operating mode that best maintains the test subjects’ disease.
  • a similar process may be performed for an individual subject to determine the operating mode that best maintains the individual subject’s disease. This process may be performed at any time including as part of an initial prescription of the ambulatory medical device.
  • a glucose level of the subject may fluctuate during the day and in response to various medicament therapies, such as insulin and/or glucagon.
  • medicament therapies such as insulin and/or glucagon.
  • One result of such therapy is that it can, if not properly calibrated, result in a series of overcorrections.
  • regulatory therapy e.g., insulin, insulin analog
  • counter-regulatory therapy e.g., glucagon, carbohydrate treatment
  • steps represent a first intervention (or first mode) of therapy that seeks to generally keep the subject’s glucose within a predetermined range of glucose values, as described herein for example with respect to FIG. 22 to help mitigate the risk of or try to avoid a hypoglycemic event.
  • this added glucagon may cause the glucose level of the subject to spike once again. This cyclical pattern may repeat itself for a time before the glucose level.
  • the glucose level control system can respond in one or more ways as a form of a second intervention or recovery mode.
  • the minimum threshold described herein e.g., Gmin or GL
  • a deep low e.g., ⁇ 70 mg/dl, ⁇ 65 mg/dl
  • an urgent/critical low e.g., ⁇ 55 mg/dl
  • the glucose level control system may reduce basal insulin deliveries (e.g., basal doses go to 0), continue to avoid delivering correction doses of insulin, provide doses of counter -regulatory agent (e.g., glucagon), generate an alarm of a low or an urgent low glucose level, and/or recommend that the subject receive a carbohydrate treatment.
  • basal insulin deliveries e.g., basal doses go to 0
  • counter -regulatory agent e.g., glucagon
  • generate an alarm of a low or an urgent low glucose level e.g., glucagon
  • the second intervention or recovery mode may continue until one or more reactivation and/or return criteria are met. For example, when the subject’s glucose level reenters a target glucose range (and, in some embodiments, after entering the target glucose range for a specified period of time), the glucose level control system can resume basal doses and/or correction doses. However, in some instances, the basal insulin delivered after a deep low may undermine the carbohydrate treatment or deep low recovery, causing the glucose level to fall back to a low or deep low level. As noted below with reference, for example, to FIG. 22, this can create oscillations that can repeat one or more times, causing recurring risk of hypoglycemia.
  • a glucose level control system can include a deep low recovery mode.
  • the recovery mode can be activated by the level of the glucose level reaching nadir, by user interaction with a carbohydrate treatment indicator (e.g., a button or menu option to indicate that treatment carbohydrates were consumed), or by some other hypoglycemic event criterion described herein.
  • the recovery mode can advantageously deter the oscillations described herein.
  • the glucose level control system In the first mode, the glucose level control system generally seeks to keep the subject at a healthy glucose level corresponding to a predetermined or desired glucose level, which may be personalized for the particular subject or set of subjects, and to try to avoid or mitigate hypoglycemic and/or hyperglycemic events, or even the risk of such events. Oscillations and overcorrections, such as those described herein, may create risks of hypoglycemic and/or hyperglycemic events. This is a first intervention that the glucose level control system 3100 implements to seek to maintain a first order level of protection against unhealthy or risky glucose levels.
  • a control algorithm in the first mode or first intervention, generates a dose control signal based on the glucose level signal.
  • This dose control signal can be configured to cause the medicament pump to administer glucose control therapy that includes basal doses of regulatory medicament, meal doses/boluses of regulatory medicament, correction doses of regulatory medicament, and/or doses of counter-regulatory medicament to the subject.
  • the regulatory medicament may be insulin, an insulin analog, or some other medicament.
  • the counter-regulatory medicament may be glucagon or glucose.
  • FIG. 22 shows an example glucose-time plot 3000 showing oscillations in a glucose level 3004 of a hypothetical subject.
  • the glucose-time plot 3000 indicates the glucose level G over time t.
  • a maximum glucose level GM e.g., Gmax 1520 described herein
  • a minimum glucose level GL e.g., Gmin 1522 described herein
  • a glucose level control system may provide basal and correction doses of medicament to a subject.
  • the maximum glucose level GM and a minimum glucose level GL are represented by a low glucose threshold 3008 and a high glucose threshold 3012, respectively, which may represent a target glucose range.
  • GL may between 65mg/dL and 75 mg/dL
  • GM may be between 175 mg/dL and 185 mg/dL
  • the system may include a Gset (not shown in FIG. 22) that represents an intermediate value between GL and GM and it may be between 70 mg/dL and 180 mg/dL.
  • the Gset may represent a predetermined target glucose level for a particular subject at a particular time.
  • the glucose level 3004 rises above the high glucose threshold 3012 (e.g., first threshold glucose level) at which point additional doses of regulatory medicament, such as correction doses, are provided. However, as shown, the glucose level 3004 falls thereafter below the low glucose threshold 3008 at time tbl, at which point the glucose level control system may stop delivery of insulin medicament. Despite the first intervention of the system of stopping administration of insulin, the glucose level 3004 may continue to drop to a potentially dangerous level as illustrated, where the hypothetical subject experiences a hypoglycemic event. Although while in the first mode, the glucose level control system seeks to avoid any hypoglycemic events, such events may nevertheless occur.
  • the high glucose threshold 3012 e.g., first threshold glucose level
  • systems described herein may enter a second mode or a recovery mode.
  • This recovery mode serves as a second intervention to help allow the subject’s glucose level to recover while providing further protection against overcorrections, such as those shown in FIG. 22.
  • the glucose level control system can reduce and/or suspend regulatory medicament (e.g., insulin) delivery until one or more criteria are satisfied.
  • the one or more criteria can include reactivation criteria and/or return criteria. If reactivation criteria are satisfied, the glucose level control system may resume or both of basal and/or correction doses. If return criteria are satisfied, the glucose level control system may exit the recovery mode or second intervention and reenter the first mode or first intervention.
  • the reactivation and/or return criteria may include one or more threshold durations and/or threshold glucose levels.
  • a threshold duration can be fixed or dynamic. Additionally or alternatively, a threshold glucose level can be fixed or dynamic.
  • the reactivation criteria and/or the return criteria can each include any combination of fixed and/or dynamic thresholds.
  • the reactivation criteria may include a fixed threshold duration and a dynamic threshold level. Other variations are possible. Additionally or alternatively, the return criteria can include any combination of fixed and/or dynamic thresholds.
  • Fixed thresholds do not depend on other factors (e.g., level of nadir, rate of insulin delivery, rate of glucose level change, direction of glucose level change, availability of counter -regulatory medicament delivery, weight of the subject, glucose level history of the subject, etc.), including other thresholds, but instead are predetermined and unchanging.
  • dynamic thresholds may depend on one or more factors and or may change in response to a change in another factor.
  • a dynamic threshold duration e.g., recovery threshold duration, return threshold duration
  • the threshold duration may be shorter. Additionally or alternatively, if counter-regulatory dosing is not available, the threshold duration may be longer. These relationships may help maintain a glucose level within the predetermined target glucose range. Other factors on which dynamic variables are based are described herein.
  • Threshold durations e.g., fixed threshold duration, dynamic threshold duration
  • threshold glucose levels e.g., fixed threshold glucose level, dynamic threshold glucose level
  • threshold glucose levels may be reactivation threshold glucose levels and/or return threshold glucose levels, depending on the situation.
  • a threshold duration may be about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 45 minutes, about 60 minutes, about 90 minutes, about 120 minutes, about 150 minutes, about 180 minutes, any duration therein, or fall within a duration range having any of those values as endpoints
  • Satisfaction of certain (including all) reactivation criteria can result in the glucose level control system instructing one or both of basal and/or correction doses of regulatory medicament.
  • certain (including all) return criteria e.g., one or more return threshold durations, one or more return threshold glucose levels
  • satisfaction of certain (including all) return criteria can result in the glucose level control system returning to the first mode or first intervention, including instructing both basal and correction doses of regulatory medicament.
  • a length of a dynamic threshold duration can depend on the conditions that activated the mode (e.g., the level of nadir, the amount of carbohydrate treatment) with the dynamic threshold duration being determined by the controller/processor as discussed herein.
  • a nadir of about 40 mg/dl may result in a recovery mode duration of about 3 hours.
  • a nadir of about 45 mg/dl may result in a recovery mode duration of about 2 hours.
  • a nadir of about 50 mg/dl may result in a recovery mode duration of about 1.5 hours.
  • a nadir of about 55 mg/dl may result in a recovery mode duration of about 1 hour.
  • the threshold criteria for ending recovery mode may be based on the glucose level nadir that is determined by the controller/processor as discussed herein.
  • the threshold level may about 170 mg/dl for a glucose level nadir of 40 mg/dl.
  • the threshold level may about 150 mg/dl for a glucose level nadir of 45 mg/dl.
  • the threshold level may about 135 mg/dl for a glucose level nadir of 50 mg/dl.
  • the threshold level may about 130 mg/dl for a glucose level nadir of 55 mg/dl.
  • the threshold level may about 120 mg/dl for a glucose level nadir of 65 mg/dl.
  • the threshold level may be other values, such as about 110 mg/dl, about 130 mg/dl, or some other value described herein.
  • the threshold shutoff value may be the same, regardless of the nadir.
  • the glucose level control system may include a dynamic minimum threshold duration and dynamic threshold glucose level criteria (e.g., insulin delivery resumes or exits recovery mode after or when meeting both criteria).
  • the recovery mode shutoff threshold level and/or the minimum recovery mode duration may be determined in part on the glucose level nadir.
  • the threshold level may about 170 mg/dl with a recovery duration of about 3 hours for a glucose level nadir of 40 mg/dl.
  • the threshold level may be about 150 mg/dl with a recovery duration of about 2 hours for a glucose level nadir of 45 mg/dl.
  • the threshold level may be about 135 mg/dl with a recovery duration of about 1.5 hours for a glucose level nadir of 50 mg/dl. In some embodiments, the threshold level may be about 130 mg/dl with a recovery duration of about 1 hour for a glucose level nadir of 55 mg/dl. In still other embodiments, the threshold level may be about 120 mg/dl with a recovery duration of about 1 hour for a glucose level nadir of 65 mg/dl. In some embodiments, the threshold level may be about 110 mg/dl with a recovery duration of about 1 hour for a glucose level nadir of 65 mg/dl. In some embodiments, the threshold level may be about 130 mg/dl with a recovery duration of about 1 hour for a glucose level nadir of 65 mg/dl.
  • Return criteria and/or reactivation criteria may include a threshold glucose level rate of change (e.g., return threshold glucose level rate of change, reactivation threshold glucose level rate of change).
  • the threshold glucose level rate of change may itself be dependent on the glucose level nadir or on some other factor described herein (e.g., subject weight, duration since satisfying a hypoglycemic event criterion, etc.).
  • the return and/or reactivation threshold glucose level rate of change criteria cannot be satisfied if the rate of change of the glucose level is negative.
  • a threshold glucose level rate of change (e.g., reactivation threshold glucose level rate of change, return threshold glucose level rate of change) may be calculated over two or more sampling intervals of the subject’s sensed, calculated, inferred, or otherwise derived glucose level, including glucose level in the blood.
  • a typical or predetermined sampling interval that is continual may be about 5 minutes. The two or more sampling intervals can take place over a predetermined time period.
  • the time period may be about 3 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about an hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 9 hours, about 12 hours, about 18 hours, about 24 hours, any time period therein, or fall within any range of times having any of those values as endpoints.
  • the subject’s glucose level may be sampled continuously or substantially continuously.
  • the rate of change may be calculated over 3 sampling intervals, over 4 sampling intervals, over 5 sampling intervals, or over more sampling intervals.
  • the measurement of the glucose level may be received about once per hour, about twice per hour, about three times per hour, about four times per hour, about five times per hour, or some other time.
  • return and/or reactivation criteria may include a corresponding threshold glucose level and threshold glucose level rate of change criteria.
  • both criteria must both be met (e.g., to exit recovery mode).
  • either criterion may be satisfied.
  • These criteria may be dynamic or fixed.
  • the return threshold glucose level may be about 170 mg/dl with a return threshold glucose level rate of change of +1 mg/dl/min for a glucose level nadir of 40 mg/dl.
  • the threshold level may about 150 mg/dl with a threshold rate of change of +0.5 mg/dl/min for a glucose level nadir of 45 mg/dl.
  • the threshold level may about 135 mg/dl with a threshold rate of change of +0 mg/dl/min for a glucose level nadir of 50 mg/dl. In some embodiments, the threshold level may about 130 mg/dl with a threshold rate of change of +0 mg/dl/min for a glucose level nadir of 55 mg/dl.
  • the return and/or reactivation criteria may include a plurality of threshold glucose level rate of change criteria that are based on satisfying a corresponding threshold glucose level.
  • a first threshold glucose level rate of change may be about +2 mg/dl/min based on reaching a threshold glucose level of about 165 mg/dl.
  • a second threshold glucose level rate of change may be about +1 mg/dl/min based on reaching a threshold glucose level of about 170 mg/dl.
  • a third threshold glucose level rate of change may be about +0.5 mg/dl/min based on reaching a threshold glucose level of about 180 mg/dl.
  • a fourth threshold glucose level rate of change may be about +0.0 mg/dl/min based on reaching a threshold glucose level of about 200 mg/dl.
  • nadirs may correspond to lower threshold glucose levels. For example, in some embodiments, based on reaching a nadir of 45 mg/dl, a first threshold glucose level rate of change may be about +2 mg/dl/min based on reaching a threshold glucose level of about 140 mg/dl. At this same nadir, a second threshold glucose level rate of change may be about +1 mg/dl/min based on reaching a threshold glucose level of about 145 mg/dl. Additionally or alternatively, at this same nadir, a third threshold glucose level rate of change may be about +0.5 mg/dl/min based on reaching a threshold glucose level of about 150 mg/dl. Additionally or alternatively, at this same nadir, a fourth threshold glucose level rate of change may be about +0.0 mg/dl/min based on reaching a threshold glucose level of about 170 mg/dl.
  • a first threshold glucose level rate of change may be about +2 mg/dl/min based on reaching a threshold glucose level of about 125 mg/dl.
  • a second threshold glucose level rate of change may be about +1 mg/dl/min based on reaching a threshold glucose level of about 130 mg/dl.
  • a third threshold glucose level rate of change may be about +0.5 mg/dl/min based on reaching a threshold glucose level of about 135 mg/dl.
  • a fourth threshold glucose level rate of change may be about +0.0 mg/dl/min based on reaching a threshold glucose level of about 150 mg/dl.
  • a first threshold glucose level rate of change may be about +2 mg/dl/min based on reaching a threshold glucose level of about 120 mg/dl.
  • a second threshold glucose level rate of change may be about +1 mg/dl/min based on reaching a threshold glucose level of about 125 mg/dl.
  • a third threshold glucose level rate of change may be about +0.5 mg/dl/min based on reaching a threshold glucose level of about 130 mg/dl.
  • a fourth threshold glucose level rate of change may be about +0.0 mg/dl/min based on reaching a threshold glucose level of about 140 mg/dl.
  • the glucose level control system may reintroduce the delivery of medicament in a ramp-up fashion (e.g., at a ramp-up rate) which may also be referred to as a tapered mode. Additionally or alternatively, this ramp-up rate, as with one or more return and/or reactivation criteria described herein, may be determined in part on the glucose level nadir and/or on one or more other factors. Resuming medicament delivery may include increasing amounts of the basal doses of insulin from a partial amount to a full amount of the basal doses of insulin. Such an increase may be linear or stepwise. Medicament deliveries can be resumed over one or more steps spread out over a transition time. The transition time can depend on the conditions that triggered activation of the recovery mode, on the rate of change of glucose level, on other factors, or on a combination of factors.
  • the rate of the increase of the amounts of the basal doses of insulin based on the glucose level may be based on a rate of change of the subject’s glucose level while basal and/or correction doses of medicament have been suspended or stopped.
  • the rate of the increase may be negatively correlated with the one or more low glucose levels (e.g., the rate may be relatively lower the lower the glucose level is determined to be in comparison to the one or more low glucose levels).
  • a glucose level control system may be slow to resume insulin when recovering from a deep low glucose level (e.g., 50 mg/dl or lower). With a less serious low (e.g., 70 mg/ml), the glucose level control system may resume insulin more quickly once the glucose level recovers.
  • the depth of a nadir may be advantageous to consider when deciding when to resume insulin to avoid a roller coaster of lows.
  • the duration of reducing or suspending medicament delivery may depend at least in part on the value of the glucose level nadir and/or on one or more other factors.
  • the glucose level control system may increase the rate of increase of the amounts of the doses of medicament if the glucose level data indicates the glucose levels of the subject are increasing at a rate greater than a predetermined increase rate after or when medicament delivery has been resumed. Additionally or alternatively, the glucose level control system may decrease the rate of increase of the amounts of the basal doses of medicament if the glucose level data indicates that glucose levels of the subject are decreasing at a rate greater than a predetermined decrease rate after or when medicament delivery has been resumed.
  • the glucose level control system can be operatively coupled to an ambulatory medicament pump, such as one described herein. Additionally or alternatively, the glucose level control system may be operatively coupled to a glucose sensor (e.g., a continuous glucose monitor (CGM)).
  • CGM continuous glucose monitor
  • the glucose level control system can receive a glucose level signal from the glucose sensor and, based on the glucose level signal, determine a glucose level of the subject. In some embodiments, the glucose level control system can determine the glucose level when determining that the one or more hypoglycemic event criteria, such as that user input signals correspond to an indication of a carbohydrate treatment, have been satisfied.
  • the user input signals may be received via a user interface controller, which may be part of the glucose level control system. Additionally or alternatively, the system may receive the glucose level from a user input.
  • the glucose level control system can determine a value for the threshold glucose level and/or for the threshold duration based on the glucose level associated with a time of an indication of the carbohydrate treatment.
  • the threshold glucose level may be negatively correlated with the time associated with the indication of the carbohydrate treatment.
  • the threshold duration may be positively correlated with the time associated with the indication of the carbohydrate treatment (e.g., reaching low glucose level, indication that carbohydrate treatment has begun).
  • the glucose level of the subject may vary over time.
  • the glucose level control system may determine a value for the threshold glucose level based on a time-varying glucose level of the subj ect over a time period while doses of medicament are suspended and/or stopped.
  • the glucose level control system can determine whether the initial dose control signal indicates health-appropriate therapy. This may be determined based at least in part on the received glucose level of the subject and/or on an estimated glucose level of the subject. For example, the glucose level control system may determine that with the current rate of therapy, the subject will no longer have a glucose level that is within an acceptable range, such as that described herein.
  • the glucose level control system may determine that the initial dose control signal does not indicate health-appropriate therapy by, for example, determining a time- varying glucose level of the subject over the time period mentioned above.
  • the determination may be made by estimating an amount of insulin in the subject. Estimating the amount of insulin in the subject may include determining an amount of insulin delivered to the subject. If the total amount of insulin delivered to the subject is known, the glucose level control system may be able to estimate what an approximate glucose level of the subject may be, based on other factors already known by the glucose level control system, such as those described herein.
  • the glucose level control system may estimate the amount of insulin in the subject by determining a rate of insulin absorption in the subject. This rate of insulin absorption may be calculated using values measured and/or received by the glucose level control system. Additionally or alternatively, the rate of insulin absorption may be received by a manual input by a healthcare provider via the manual therapy control interface.
  • the glucose level control system may receive additional information in determining whether the subject is receiving health-appropriate therapy. Such additional information may include a weight of the subject or other factor described herein.
  • the glucose level control system may determine one or more of the values for certain threshold criteria (e.g., threshold glucose level, threshold duration) based at least on determining that the user input signals correspond to the indication of carbohydrate treatment.
  • the glucose level control system may generate the dose control signal based on the glucose level signal to cause the medicament pump to resume glucose control therapy based on determining that the glucose level is equal to or greater than the threshold glucose level and that the threshold duration passed since meeting the hypoglycemic event criterion.
  • the glucose level control system may determine that at least one hypoglycemic event criterion is met.
  • the hypoglycemic event criterion may be referred to as critical low criteria or something similar.
  • the hypoglycemic event may be synonymous with a subject being classified as having been hypoglycemic, although this is not necessary.
  • Hypoglycemic event criteria can include one or more criteria. Such hypoglycemic event criteria can include determining that the glucose level is equal to or less than one or more low glucose levels corresponding to the hypoglycemic event. Those one or more low glucose levels are described elsewhere herein, such as below.
  • low glucose levels may include about 40 mg/dl, about 45 mg/dl, about 50 mg/dl, about 55 mg/dl, about 60 mg/dl, about 65 mg/dl, about 70 mg/dl, any value falling therebetween, or fall within a range having endpoints therein.
  • hypoglycemic event criterion can include determining that user input signals received via the user interface controller correspond to a user indication of carbohydrate treatment.
  • a hypoglycemic event criterion can include determining that the glucose level signal indicates carbohydrate treatment by the subject and/or determining that a physiological sensor other than the glucose sensor indicates carbohydrate treatment by the subject.
  • the hypoglycemic event criterion may include an indication that a threshold amount of counter-regulatory medicament (e.g., glucagon) has been delivered to the subject.
  • a threshold amount of counter-regulatory medicament e.g., glucagon
  • the glucose level control system may provide counter- regulatory medicament after or when a subject reaches a low glucose level. As noted herein, such counter-regulatory medicament can be tailored to raise the glucose level of the subject.
  • the glucose level control system may operate in the recovery mode or second intervention described herein in which the control algorithm causes the medicament pump to not administer at least basal doses and/or correction doses of medicament to the subject until certain return and/or reactivation criteria are satisfied.
  • a basal regulatory medicament controller e.g., the basal controller 624 of FIG. 6
  • a corrective regulatory medicament controller e.g., the corrective insulin controller 626 of FIG. 6
  • a priming insulin controller e.g., the priming insulin controller 628) may also be in an off state or in a suspended state during recovery mode.
  • the glucose level control system may instruct the medicament pump to deliver counter-regulatory medicament while in the recovery mode.
  • a counter-regulatory controller e.g., the counter -regulatory agent controller 622 of FIG. 6
  • the medicament pump can provide counter-regulatory doses of a counter- regulatory medicament
  • the glucose level control system may instruct such counter- regulatory medicament delivery.
  • the glucose level control system can generate a dose control signal to cause the medicament pump to administer doses of counter -regulatory agent if the glucose level control system determines that the glucose level is equal to or less than the one or more low glucose levels.
  • the glucose level control system determines that the subject’s glucose level is equal to or greater than a threshold glucose level and/or that a threshold duration has passed since the hypoglycemic event criterion was satisfied, the glucose level control system can generate a dose control signal based on the glucose level signal to cause the medicament pump to administer basal doses of insulin to the subject.
  • the glucose level control system may operate in the recovery mode for a period of time after or when determining that the at least one hypoglycemic event criterion is met. The period of time may be about 1 second, about 2 seconds, about 5 seconds, about 10 seconds, or some other time.
  • the glucose level control system can determine the threshold glucose level based on the low glucose level. For example, as noted above, the threshold glucose level may be relatively higher for higher low glucose levels, and the threshold glucose level may be lower for lower low glucose levels. That is, in some embodiments, the threshold glucose level may be positively correlated with the level of the low glucose level. Additionally or alternatively, the threshold duration in recovery mode may be based at least in part on the threshold glucose level. For example, the threshold duration may be negatively correlated with the threshold duration. That is, the threshold duration may be longer for lower low glucose levels.
  • the glucose level control system can generate a dose control signal based on the glucose level signal received to cause the medicament pump to administer the basal doses of insulin to the subject to resume glucose control therapy in the first mode.
  • This dose control signal can be based on determining that the glucose level signal is equal to or greater than the one or more threshold glucose levels and/or that the one or more threshold durations passed since the subject reached the low glucose level.
  • one or more additional criteria e.g., return criteria
  • the additional one or more criteria may include a threshold duration (e.g., threshold return duration) that must be satisfied before the system returns to the first mode or first intervention.
  • the glucose level control system may be able to generate the dose control signal to resume glucose control therapy based on satisfaction of the one or more return criteria (e.g., determining that both the glucose level is equal to and greater than the return threshold glucose level and/or that the return threshold duration has passed).
  • the one or more return criteria may be satisfied directly after the hypoglycemic event criterion is satisfied or after reactivation criteria have been satisfied.
  • the one or more return criteria may be dependent on the hypoglycemic event criterion, such as a time when the hypoglycemic event criterion is satisfied. For example, the glucose level control system may resume medicament delivery if the return threshold duration has passed since the hypoglycemic event criterion has been satisfied.
  • FIG. 23 shows an example glucose level control system 3100 configured to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after or when the subject experiences a hypoglycemic event indicated by a low glucose level or after or when the subject receives carbohydrate treatment.
  • “Modify” may refer to its plain and ordinary meaning, and may include adjusting, updating, complementing, temporarily overriding, or permanently overriding a previous (e.g., automated or manual) instruction.
  • the glucose level control system 3100 can command administration of modified glucose control therapy to a subject via a medicament pump 3120.
  • the glucose level control system 3100 can include one or more of a medicament delivery interface 3104, user interface controller 3108, and/or a data interface 3116.
  • the data interface 3116 and/or the medicament delivery interface 3104 may include a wireless and/or wired data interface. Additionally or alternatively, the data interface 3116 and/or the medicament delivery interface 3104 can include a short-range wireless data interface.
  • the glucose level control system 3100 can also include a non-transitory memory 3118 and an electronic hardware processor 3119. The processor 3119 may execute instructions stored on the memory 3118 to perform various functions described herein.
  • the medicament delivery interface 3104 may be in communication (e.g., wired, wireless) with the medicament pump 3120 (e.g., via a medicament pump connection 3132). Additionally or alternatively, the data interface 3116 may be in communication with the medicament pump 3120. The data interface 3116 can be in communication with a network 3124 (e.g., via a network connection 3136), and/or a user device connection 3140 (e.g., via a user device connection 3140). Each of the connections 3132, 3136, 3140 may be one-way or two-way. The medicament delivery interface 3104 may also be in communication with other elements of the glucose level control system 3100, such as the pump mechanism 3122 and/or the pump controller 3123.
  • the communication with the other elements within the glucose level control system 3100 may be via a wired connection.
  • the medicament pump 3120 can represent one or a plurality of medicament pumps. However, for simplicity, reference to the medicament pump 3120 will represent one or a plurality of medicament pumps.
  • the medicament pump 3120 may be any medicament pump described herein, such as the pump 100, the pump 212, and/or a pump within the glucose level control system 510.
  • the medicament pump 3120 is a medicament pump coupled to the subject during in-patient therapy delivery.
  • the pump controller 3123 is configured to direct medicament from a medicament reservoir to the subject using the pump mechanism 3122.
  • the data interface 3116 may be able to communicate (e.g., wirelessly, via wired connection) with a network 3124 and/or a user device 3128 via respective connections 3136, 3140.
  • the medicament delivery interface 3104 may be configured to communicate with the medicament pump 3120 via the glucose sensor connection 3132.
  • the data interface 3116 can communicate with the medicament pump 3120, such as via a wireless connection.
  • the medicament pump 3120 can include a pump mechanism 3122 and a pump controller 3123.
  • the medicament delivery interface 3104 communicates with the pump controller 3123 of the medicament pump 3120.
  • the network 3124 may include any wired network, wireless network, or combination thereof.
  • the network 3124 may be a personal area network, local area network, wide area network, over-the-air broadcast network (e.g., for radio or television), cable network, satellite network, cellular telephone network, or combination thereof.
  • the network 3124 may be a publicly accessible network of linked networks, possibly operated by various distinct parties, such as the Internet.
  • the network 3124 may be a private or semi -private network, such as a corporate or university intranet.
  • the network 3124 may include one or more wireless networks, such as a Global System for Mobile Communications (GSM) network, a Code Division Multiple Access (CDMA) network, a Long Term Evolution (LTE) network, or any other type of wireless network.
  • GSM Global System for Mobile Communications
  • CDMA Code Division Multiple Access
  • LTE Long Term Evolution
  • the network 3124 can use protocols and components for communicating via the Internet or any of the other aforementioned types of networks.
  • the protocols used by the network 3124 may include Hypertext Transfer Protocol (HTTP), HTTP Secure (HTTPS), Message Queue Telemetry Transport (MQTT), Constrained Application Protocol (CoAP), and the like. Protocols and components for communicating via the Internet or any of the other aforementioned types of communication networks are well known to those skilled in the art and, thus, are not described in more detail herein.
  • the network 3124 may comprise the “cloud.”
  • the network 3124 may include a remote computing environment.
  • a user device 3128 may further include a glucose sensor (e.g., a continuous glucose monitor (CGM)) that is operatively connected to the subject.
  • CGM continuous glucose monitor
  • the user devices 3128 can be any computing or other electronic communication device such as a desktop, laptop or tablet computer, personal computer, tablet computer, wearable computer, server, personal digital assistant (PDA), PDM, hybrid PDA/mobile phone, mobile phone, smartphone, set top box, voice command device, digital media player, and the like.
  • PDA personal digital assistant
  • a user device 3128 may execute an application (e.g., a browser, a stand-alone application) that allows a user to access and interact with interactive graphical user interfaces as described herein.
  • the glucose level control system 3100 may be operatively coupled to and/or include a user interface that can receive user inputs.
  • Inputs on the touchscreen display may be registered by any touch technology including, but not limited to capacitive and resistive sensing.
  • the touchscreen display may be a part of a mobile computing device, such as a cellular phone, tablet, laptop, computer, or the like (e.g., the user device 3128).
  • the touchscreen display may have a computing component for interpreting and executing instructions from the processor 3119. Thus, the touchscreen display can follow instructions that are directed by the processor 3119.
  • the touchscreen display may display buttons, alphanumeric characters, symbols, graphical images, animations, or videos.
  • the user interface is not a touchscreen display.
  • the user interface may comprise one or more mechanical buttons.
  • the user interface may include an alert generator, such as a light emitter, a speaker, a haptic feedback system, or other sensory alert system.
  • the glucose level control system 3100 can be configured to transmit an initial dose control signal to a pump controller of the medicament pump 3120.
  • the initial dose control signal may be configured to cause the medicament pump 3120 to infuse an initial amount of medicament into a subject.
  • This initial amount of medicament may be a regular (e.g., basal) rate of medicament.
  • the glucose level of the subject may be obtained in one or more ways. For example, the glucose level may be estimated or predicted based on a previous measurement and/or on a user input. Additionally or alternatively, a nurse or other healthcare provider may take a measurement of the glucose level by pricking the subject’s finger and entering the value into the glucose level control system 3100. This glucose measurement may be taken periodically (e.g., regularly).
  • the measurement may be taken about once per hour, about twice per hour, about three times per hour, about four times per hour, about five times per hour, or some other time.
  • the measurements may be taken at regular intervals over a time period in some cases.
  • the time period may be about an hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 9 hours, about 12 hours, about 18 hours, about 24 hours, any time period therein, or fall within any range of times having any of those values as endpoints.
  • the time period is about an hour.
  • the measurements may be taken at irregular points after the initial dose control signal has been received by the medicament pump 3120.
  • the glucose level control system 3100 can receive the glucose level of the subject via a manual input into the glucose level control system 3100 (e.g., via a manual therapy control interface).
  • a continuous glucose monitor may be coupled to the subject and may determine a glucose level of the subject, such as a glucose level of the subject within the interstitial fluid in the subcutaneous depot of the subject.
  • the CGM may determine the glucose level of the subject by receiving an electrochemical signal from the subject’s blood and/or interstitial fluid.
  • the CGM may transmit the glucose level of the subject wirelessly or via a wired connection (e.g., via the data interface 3116) to the glucose level control system 3100.
  • the glucose level control system 3100 may include an alarm screen interface.
  • the glucose level control system may generate a display on the alarm screen interface one or more alarm status indicators corresponding to the one or more low glucose levels.
  • the one or more status indicators can include an indication of the one or more threshold criteria (e.g., a threshold glucose level, a threshold duration), what the hypoglycemic event criterion is, whether basal and/or correction doses are being delivered, and/or any other indicator.
  • glucose level control system 3100 Some of the data that is passed to/from the glucose level control system and/or generated by the glucose level control system 3100 may be stored by the glucose level control system 3100.
  • the storage may be local to the glucose level control system 3100 (e.g., on the memory 3118) or remote.
  • the glucose level control system may store glucose level data corresponding to one or more glucose levels after or when resuming delivery of medicament.
  • Such stored data may allow the glucose level control system to adapt one or more of the threshold criteria (e.g., reactivation criteria, return criteria), a rate of increase of doses of insulin (e.g., basal, correction), an amount of time that has passed (e.g., since a hypoglycemic event criterion has been satisfied, since the one or more reactivation criteria have been satisfied).
  • Adapting the one or more threshold criteria, the rate of increase of the amounts of the basal doses of insulin, or the amount of time that has passed can include determining whether the adaptation results in a reduced occurrence of blood glucose excursions and/or a reduced risk of an occurrence of a hypoglycemic event, such as that described herein with respect to FIG. 16.
  • the glucose level control system can include a quality control feature to ensure that the glucose control therapy that it is instructing is promoting improvements in health of the subject.
  • the glucose level control system 3100 can determine whether the initial dose control signal indicates health-appropriate therapy. This may be determined based at least in part on the received glucose level of the subject. For example, the glucose level control system 3100 may determine that with the current rate of therapy (e.g., in the first mode), the subject will no longer have a glucose level that is within an a predetermined or desired range, such as that described herein. The glucose level control system 3100 may determine that the initial dose control signal does not indicate health-appropriate therapy by, for example, determining a time-varying glucose level of the subject over the time period mentioned above.
  • the determination may be made by estimating an amount of insulin in the subject. Estimating the amount of insulin in the subject may include determining an amount of insulin delivered to the subject. If the total amount of insulin delivered to the subject is known, the glucose level control system 3100 may be able to estimate what an approximate glucose level of the subject may be, based on other factors already known by the glucose level control system 3100, such as those described herein. Additionally or alternatively, the glucose level control system 3100 may estimate the amount of insulin in the subject by determining a rate of insulin absorption in the subject. This rate of insulin absorption may be calculated using values previously measured and then received by the glucose level control system 3100. Additionally or alternatively, the rate of insulin absorption may be received by a manual input by a healthcare provider via the manual therapy control interface. The glucose level control system 3100 may receive additional information in determining whether the subject is receiving health-appropriate therapy.
  • the glucose level control system 3100 may be configured to receive a glucose level signal from a glucose sensor operatively connected to the subject. Based on this glucose level signal, the glucose level control system 3100 may determine a glucose level of the subject. The glucose level control system 3100 may determine that the glucose level is equal to or greater than a first threshold glucose level. This first threshold glucose level may correspond to a glucose level that is within a predetermined or desired range of glucose level for a subject. Thus, a glucose level at or above the first threshold glucose level may generally indicate that a subject is not currently at risk of hypoglycemia. The first threshold glucose level may correspond to a GL (see FIG.
  • the glucose level control system 3100 may determine that mitigation of a hypoglycemic event using the first intervention or first mode was not sufficient after determining that at least one hypoglycemic event criterion is met.
  • a hypoglycemic event criterion may be any such hypoglycemic event criterion described herein.
  • the hypoglycemic event criterion may include one or more of a plurality of hypoglycemic event criteria, such as determining that the glucose level is equal to or less than one or more low glucose levels corresponding to a hypoglycemic event.
  • the one or more low glucose levels may correspond to a glucose level of about 40 mg/dl, about 45 mg/dl, about 50 mg/dl, about 55 mg/dl, about 65 mg/dl, about 70 mg/dl, about 75 mg/dl, any value therein or fall within a range having any of those values as endpoints. Different of these values may have an associated different response by the glucose level control system 3100 since each level signals a different level of concern of hypoglycemia.
  • Another example hypoglycemic event criterion includes determining that user input signals (e.g., received via the user interface controller 3108) correspond to a user indication of carbohydrate treatment.
  • user input signals e.g., received via the user interface controller 3108
  • this may be an indication that the subject identifies himself or herself to be at a risk of hypoglycemia.
  • a user e.g., the subject
  • the hypoglycemic event criterion may include determining that the glucose level signal indicates the carbohydrate treatment by the subject.
  • the glucose level control system 3100 may receive an indication of a subject’s increase in glucose level after or during a relative low and determine that the increase in glucose level may be an indication of the initiation of the carbohydrate treatment. This may occur even without the user interfacing with the glucose level control system 3100. In this way, the glucose level control system 3100 may be able to receive signals from a glucose sensor to avoid user error and make appropriate adjustments.
  • a further example of a hypoglycemic event criterion includes determining that a physiological sensor other than the glucose sensor indicates carbohydrate treatment by the subject.
  • a physiological sensor could include a sensor that tracks activity level of the subject, such as a step tracker.
  • Other examples of a physiological sensor include a heartrate sensor, a breath rate sensor, or a blood pressure sensor.
  • the glucose level control system 3100 may be configured to enter a second mode or recovery mode.
  • the recovery mode may include a reactivation mode and/or a deep low recovery mode that may depend on a level of glucose level nadir as discussed herein.
  • the glucose level control system 3100 does not cause administration of at least one of basal doses and/or correction doses of medicament to the subject.
  • the administration of the at least one of the basal and/or correction doses may be suspended (at least temporarily) during recovery mode.
  • the glucose level control system 3100 instructs the medicament pump 3120 to suspend both basal doses and correction doses.
  • any additional medicament e.g., insulin, insulin analog
  • any additional medicament may further exacerbate an already-risky situation that the subject could experience (or has experienced) a hypoglycemic event.
  • the suspension of the one or more of the basal and/or correction doses of medicament may last until one or more threshold criteria are met.
  • the one or more threshold criteria may include a certain amount of time since the one or more hypoglycemic event criteria were satisfied. This amount of time may be referred to as a recovery threshold duration, but reference to a reactivation threshold duration or a return threshold duration may be used depending on the result of the satisfaction of either.
  • the recovery threshold duration may include a minimum amount of time or a maximum amount of time.
  • a reactivation criterion may include a maximum duration of time, where the system enters a reactivation mode after the passage of a maximum duration.
  • the system may enter into the first mode after passage of a maximum duration.
  • the system may operate a minimum duration in the reactivation mode once the system has entered into the reactivation. Accordingly, recovery duration may include a minimum recovery duration, maximum recovery duration, minimum duration, and/or maximum duration.
  • the recovery threshold duration or recovery duration may be about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 45 minutes, about 60 minutes, about 90 minutes, about 120 minutes, about 150 minutes, about 180 minutes, any duration therein, or fall within a duration range having any of those values as endpoints.
  • Having a recovery threshold duration of time e.g., a reactivation threshold duration, a return threshold duration
  • the glucose level control system 3100 begins dosing basal and/or correction doses of regulatory medicament.
  • the one or more reactivation criteria may additionally or alternatively include determining that the subject’s glucose level is equal to or greater than a reactivation threshold level.
  • reactivation criteria may include one or more reactivation threshold levels, reactivation threshold durations, and/or reactivation threshold glucose level rates of change.
  • a reactivation threshold level may be about 90 mg/dl, about 95 mg/dl, about 100 mg/dl, about 105 mg/dl, about 110 mg/dl, about 115 mg/dl, about 120 mg/dl, about 125 mg/dl, about 130 mg/dl, about 135 mg/dl, about 140 mg/dl, about 145 mg/dl, about 150 mg/dl, any level therein, or fall within a range having any of those values as endpoints.
  • Such a reactivation threshold level may help reduce the risk that the glucose level control system 3100 prematurely instructs resuming of the one or more of the basal and/or correction doses of medicament.
  • a reactivation threshold duration may be about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 45 minutes, about 60 minutes, about 90 minutes, about 120 minutes, about 150 minutes, about 180 minutes, about 240 minutes, about 360 minutes, any duration therein, or fall within a duration range having any of those values as endpoints.
  • a reactivation threshold glucose level rate of change may be about 0.1 mg/dl/min, about 0.2 mg/dl/min, about 0.3 mg/dl/min, about 0.5 mg/dl/min, about 0.8 mg/dl/min, about 1.0 mg/dl/min, about 1.25 mg/dl/min, about 1.5 mg/dl/min, about 1.75 mg/dl/min, about 2.0 mg/dl/min, about 2.25 mg/dl/min, about 2.5 mg/dl/min, about 3.0 mg/dl/min, any rate therein, or fall within a rate range having any of those values as endpoints.
  • two or more of the reactivation criteria may be dependent on other of the one or more of the reactivation criteria.
  • a reactivation threshold duration may be based at least in part on the reactivation threshold level.
  • a lower reactivation threshold level may require, for instance, a longer reactivation threshold duration (e.g., a negatively correlated relationship) to satisfy the one or more reactivation criteria. This may promote a safety against a risk of a false positive or other misreading of the subject’s higher (e.g., above the reactivation threshold level) glucose level.
  • the reactivation threshold level and the reactivation threshold duration may be positively correlated (e.g., a lower reactivation threshold level may require a shorter reactivation threshold duration) to guard against a subject slipping into a different kind of risk, such as a hyperglycemic event.
  • a separate baseline reactivation threshold level may exist in some embodiments.
  • the baseline reactivation threshold may be a minimum threshold level, below which if the subject’s glucose level falls, the amount of time already banked for fulfilling the reactivation threshold duration criterion (if applicable) is reset, reduced, or paused. Banked time may be used to satisfy a threshold duration criterion but may be paused or modified as noted above.
  • the time for fulfilling the reactivation threshold duration criterion may resume only after or when the glucose level reaches or exceeds the baseline reactivation threshold level and/or the reactivation threshold level.
  • the time may begin to run for fulfilling the reactivation threshold duration requirement once the subject’s glucose level is determined to be, for example, 120 mg/dl.
  • the subject may have to wait for the glucose level to rise above the 100 mg/dl (or, in some embodiments, the 120 mg/dl) level before the clock continues to run for fulfilling the reactivation threshold duration requirement.
  • the amount of time banked toward fulfilling the reactivation threshold duration is reduced (e.g., instantly or gradually) to zero.
  • This baseline reactivation threshold level may be lower than the reactivation threshold level described herein. However, in some embodiments, the baseline reactivation threshold level and the reactivation threshold level are the same.
  • the baseline reactivation threshold level may represent a new threshold below which if the glucose level falls, a new hypoglycemic event criterion is satisfied and a new clock for satisfying a threshold duration begins anew.
  • the baseline reactivation threshold level may be determined after or when the glucose level control system 3100 enters the second mode. If the glucose level falls below the baseline reactivation threshold, any banked time since determining that the hypoglycemic event criterion has been met may be reset, and a new timer may begin with new banked time starting at zero. Such an event may be considered as entering the recovery mode and operating in the recovery mode as discussed herein when entering from the first mode even though in such an instance, the recovery mode is entered or restarted while in the recovery mode.
  • the glucose level control system 3100 may instruct the medicament pump 3120 to resume one or both of the basal and/or correction doses medicament doses that were stopped or suspended. For example, once the one or more reactivation criteria have been satisfied, the glucose level control system 3100 may instruct the medicament pump 3120 to resume the basal doses without administering correction doses after or when reaching a threshold glucose level. In some embodiments, the glucose level control system 3100 may instruct the medicament pump 3120 do not administer the correction doses until the glucose level control system 3100 returns to operation in the recovery mode, such as for example entering the first mode when a threshold duration has passed while administering basal doses after reaching threshold glucose level.
  • the glucose level control system 3100 may resume medicament doses (e.g., basal and/or correction doses) gradually.
  • the glucose level control system 3100 may enter a third mode, reactivation mode, or transition mode, which may be considered to be part of the recovery mode or second intervention.
  • the glucose level control system 3100 may provide a third intervention to further promote healthy and reduced -risk glucose levels.
  • the glucose level control system 3100 may instruct gradually increased amounts and/or frequency of basal and/or correction doses of medicament.
  • Such gradually increased doses of medicament may be referred to as ramp-up doses and/or may be associated with a ramp-up rate or ramp-up frequency, as noted above.
  • the ramp-up dose amount and/or frequency during reactivation mode may be lower than a corresponding dose amount/frequency during the first mode, and/or may be higher than a corresponding dose amount/frequency during the recovery mode.
  • the gradually increased amounts and/or frequency of basal doses may be lower than corresponding amounts and/or frequency of basal doses that are instructed during the first mode described herein.
  • the glucose level control system 3100 may instruct gradually increased amounts of correction doses of medicament. In some embodiments, the glucose level control system 3100 does not instruct correction doses at all during reactivation mode (e.g., only basal doses are instructed while no correction doses are instructed).
  • the gradual increase of the basal and/or correction doses during reactivation mode may occur during passage of a threshold amount of time.
  • This threshold amount of time may be about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 45 minutes, about 60 minutes, about 90 minutes, about 120 minutes, about 150 minutes, about 180 minutes, any duration therein, or fall within a duration range having any of those values as endpoints.
  • This passage of time can help improve the health and safety of the subject to avoid risky fluctuations of glucose level.
  • the glucose level control system 3100 may regularly determine (e.g., receive measurements, estimate, predict) the subject’s glucose level during this time.
  • the threshold amount of time in the reactivation mode may be dependent on whether and/or to what extent the determined glucose level of the subject is above the baseline reactivation threshold and/or the reactivation threshold described herein.
  • a threshold glucose level e.g., the baseline reactivation threshold level, the reactivation threshold level
  • the clock for counting the threshold amount of time in the reactivation mode may be reset, paused, or reduced.
  • the time may not restart (or re-begin) until the glucose level reaches the baseline reactivation threshold level and/or the reactivation threshold level.
  • the baseline reactivation threshold level may represent a new threshold below which if the glucose level falls a new hypoglycemic event criterion may be satisfied, which may cause the glucose level control system 3100 to enter the second mode anew. Any banked time since determining that the original hypoglycemic event criterion has been met may be reset, and a new timer may begin with new banked time starting at zero.
  • the threshold amount of time and/or rate of change of the gradual increase in basal and/or correction doses during reactivation mode may be dependent in part on one or more of the one or more hypoglycemic event criteria and/or reactivation criteria.
  • the threshold amount of time may be negatively correlated to the one or more low glucose levels.
  • the rate of change of the gradual increase in basal and/or correction doses may be negatively correlated to the reactivation threshold level.
  • the reactivation threshold level may be about 110 mg/dl with a rate of change of about 1 mg/dl/min
  • the reactivation threshold level may be about 120 mg/dl with a rate of change of about 0.5 mg/dl/min
  • the rate of change of the gradual increase in basal and/or correction doses may be sufficient to cause a glucose level rate change of about 0.1 mg/dl/min, about 0.2 mg/dl/min, about 0.3 mg/dl/min, about 0.5 mg/dl/min, about 0.7 mg/dl/min, about 1 mg/dl/min, about 1.5 mg/dl/min, about 2 mg/dl/min, about 2.5 mg/dl/min, about 3 mg/dl/min, about 3.5 mg/dl/min, about 4 mg/dl/min, about 5 mg/dl/min, any value therein, or fall within a range having any of those values as endpoints.
  • the amount of basal and/or correction doses that can be used to achieve the target glucose level rate of change may be dependent on one or more variables, such as weight of the subject, time of day, level of activity of the subject, or some other factor.
  • a unit of insulin may reduce a subject’s glucose level by between about 5 mg/dl and about 60 mg/dl, depending on one or more factors, such as those described herein.
  • a delivery of regulatory medicament may be provided at a rate of about 0.1 units/hour (u/h), about 0.2 u/h, about 0.3 u/h, about 0.5 u/h, about 0.8 u/h, about 1.0 u/h, about 1.2 u/h, about 1.5 u/h, about 2.0 u/h, about 2.5 u/h, about 3.0 u/h, about 3.5 u/h, any rate therein, or fall within a range having any of those rates as endpoints.
  • the value of glucose level rate of change in a specific embodiment, as noted above, may be based at least in part on the threshold amount of time and/or on one or more of the one or more hypoglycemic event criteria described herein.
  • the glucose level control system 3100 may transition back to the first mode (e.g., from the reactivation mode, from the recovery mode) if one or more return criteria are met.
  • the return criteria can include one or more criteria, such as one or more return threshold levels, return threshold durations, and/or return threshold glucose level rates of change.
  • the return criteria may include determining that the glucose level of the subject is equal to or greater than a return threshold level and/or a return threshold duration.
  • the return threshold level may use any of the values described herein for the baseline reactivation threshold level and/or the reactivation threshold level. In some embodiments, the return threshold level is the same as the baseline reactivation threshold level and/or the reactivation threshold level.
  • the return threshold duration may be any of the values described herein for the reactivation threshold duration, and in some embodiments is the same as the reactivation threshold duration. In some embodiments, the return threshold level is greater than the reactivation threshold level described herein, and/or the return threshold duration is shorter than the reactivation threshold duration described herein.
  • the glucose level control system 3100 will update the dose control signal to include basal and correction doses of medicament, as when in the first mode.
  • the basal controller and the correction controller of the glucose level control system 3100 can again instruct basal and correction doses.
  • the priming boluses of medicament may also resume if they were suspended while in recovery mode. Resuming the medicament doses that were stopped may occur essentially immediately or may begin gradually.
  • the return threshold duration requirement may be satisfied if, for example, a glucose level is determined to be above the return threshold level a specified number of times.
  • the return criteria may be satisfied if the glucose level control system 3100 determines (e.g., receives measured glucose levels of the subject) within the return threshold duration that each of a plurality of glucose measurements are each equal to or greater than the return threshold level.
  • the return threshold duration may be about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 45 minutes, about 60 minutes, about 90 minutes, about 120 minutes, about 150 minutes, about 180 minutes, about 240 minutes, about 360 minutes, any duration therein, or fall within a duration range having any of those values as endpoints.
  • a return threshold glucose level rate of change may be about 0.1 mg/dl/min, about 0.2 mg/dl/min, about 0.3 mg/dl/min, about 0.5 mg/dl/min, about 0.8 mg/dl/min, about 1.0 mg/dl/min, about 1.25 mg/dl/min, about 1.5 mg/dl/min, about 1.75 mg/dl/min, about 2.0 mg/dl/min, about 2.25 mg/dl/min, about 2.5 mg/dl/min, about 3.0 mg/dl/min, any rate therein, or fall within a rate range having any of those values as endpoints.
  • the return threshold duration may be calculated from when the glucose level control system 3100 determines that the one or more hypoglycemic event criteria have been met.
  • the glucose level control system 3100 may re-enter the first mode directly from the recovery mode without entering into a reactivation mode.
  • the return threshold duration is calculated from when the glucose level control system 3100 determines that the one or more reactivation criteria described herein have been met.
  • the return criteria can be satisfied in a plurality of ways. Additionally or alternatively, the return criteria may include a plurality of threshold durations, a plurality of threshold glucose levels, and/or a plurality of threshold rates of change of glucose levels. For example, in some embodiments, a first way to satisfy the return criteria may be to satisfy a first return threshold duration that is calculated from satisfying a hypoglycemic event criterion, and a second way to satisfy the return criteria may be to satisfy a second return threshold duration (e.g., also calculated from satisfying the hypoglycemic event criterion) that is, for example, shorter than the first return threshold duration, and also satisfy a return threshold glucose level while satisfying the second return threshold duration.
  • a first way to satisfy the return criteria may be to satisfy a first return threshold duration that is calculated from satisfying a hypoglycemic event criterion
  • a second way to satisfy the return criteria may be to satisfy a second return threshold duration (e.g., also calculated from satisfying the hypoglycemic event cri
  • a first way to satisfy the return criteria may be to satisfy a first return threshold duration while satisfying a threshold rate of change of glucose level
  • a second way to satisfy the return criteria may be to satisfy a second return threshold duration while satisfying a threshold glucose level.
  • a first way to satisfy the return criteria may be to satisfy a first return threshold duration (e.g., calculated since determining that a hypoglycemic event criterion is satisfied), and a second way to satisfy the return criteria may be to first satisfy a reactivation threshold level (e.g., thereby resuming basal doses) followed by satisfying a second return threshold duration (e.g., calculated from a determination that the reactivation threshold level is satisfied).
  • a first return threshold duration e.g., calculated since determining that a hypoglycemic event criterion is satisfied
  • a second way to satisfy the return criteria may be to first satisfy a reactivation threshold level (e.g., thereby resuming basal doses) followed by satisfying a second return threshold duration (e.g., calculated from a determination that the reactivation threshold level is satisfied).
  • FIG. 24 shows an example glucose-time plot 3200 showing a reactivation threshold duration 3216 that initiates after or when a glucose level 3204 drops below a threshold low glucose level 3208.
  • the embodiment shown in FIG. 24 includes both reactivation and return criteria.
  • the reactivation criteria includes satisfying either a reactivation threshold duration 3216 or a reactivation threshold level 3212 at GR, and the return criteria includes a return threshold duration 3220.
  • the reactivation threshold duration 3216 is followed by the return threshold duration 3220.
  • the glucose level 3204 begins relatively high but experiences a drop shortly after a time tc where, for example, the hypothetical subject receives a correction dose of regulatory medicament or experiences a low glucose level for any other reason.
  • the drop in the glucose level 3204 continues until a hypoglycemic event occurs at th, where the glucose level 3204 drops below the threshold low glucose level 3208. As with some embodiments of a glucose level control system described herein, this may result in triggering a suspension of basal and correction doses of regulatory medicament, which corresponds to entering recovery mode and initiating the second intervention. Additionally or alternatively, it may trigger delivery of counter -regulatory medicament. Entering recovery mode may also initiate a clock to begin satisfaction of the reactivation threshold duration 3216. A relatively steady increase in the glucose level 3204 results thereafter through time treact when the reactivation threshold duration 3216 has been satisfied, even before reaching the reactivation threshold level 3212.
  • the embodiment shown in FIG. 24 requires satisfaction of either the reactivation threshold duration or the reactivation threshold glucose level to satisfy the reactivation criteria.
  • the glucose level control system may instruct basal doses to resume and be delivered to the subject after or with satisfaction of the reactivation threshold duration 3216. This may correspond to the initiation of the reactivation mode described herein.
  • the time for satisfying the return threshold duration 3220 may begin at time treact when the reactivation mode begins.
  • basal doses resume, and may include ramping of the basal doses as discussed herein.
  • the return threshold duration 3220 may be satisfied at time treturn. As in the embodiment shown, this causes the glucose level control system to send a dose control signal that is configured to cause delivery of both basal and correction doses of regulatory medicament by the medicament pump. Thus, the glucose level control system returns to the first mode or first intervention.
  • the glucose level control system may instruct a gradual increase in basal doses of medicament (e.g., ramp-up basal doses). Additionally or alternatively, the glucose level control system may instruct a gradual increase in correction doses of medicament (e.g., ramp-up correction doses).
  • FIG. 25 shows another example glucose-time plot 3300 showing a hypothetical scenario where the return criteria include both a return threshold level 3312 (which may also be referred to as a recovery threshold glucose level) and a return threshold duration 3316.
  • the return criteria are not satisfied until after a glucose level 3304 has reached the return threshold level 3312 (at GRT) and a return threshold duration 3316 has passed after the glucose level 3304 experiences a hypoglycemic event (e.g., the glucose level 3304 falls below the low glucose level 3308).
  • the glucose level 3304 After starting at a relatively high level, the glucose level 3304 experiences a glucose level relative peak near time tc (e.g., due to dose of corrective insulin, due to behavior change unnoticed by the glucose level control system, etc.) and then begins a fairly rapid fall until time th when the glucose level 3304 falls below the low glucose level 3308. This triggers a satisfaction of a hypoglycemic event criterion.
  • the glucose level control system enters a recovery mode and instructs a second intervention where basal and correction doses are suspended for up to a return threshold duration 3316 (since in the embodiment shown the return threshold duration 3316 represents a maximum threshold duration rather than a minimum threshold duration).
  • an associated glucose level control system may instruct resumed basal and correction doses after or when the glucose level 3304 reaches the return threshold level 3312 at time tr2, the embodiment shown maintains the suspension the basal and correction doses of medicament until time trl, when both the return threshold duration 3316 and the return threshold level 3312 have been satisfied, thus satisfying both return criteria.
  • FIG. 26 shows another example glucose-time plot 3400 showing a hypothetical scenario where the return criteria includes a return threshold duration 3416 (which may also be referred to as a maximum duration in, for example, the recovery mode).
  • the return criteria are satisfied once the return threshold duration 3416 after the glucose level 3404 indicates a hypoglycemic event (e.g., the glucose level 3404 falls below the low glucose level 3408).
  • the glucose level 3404 falls until time th when the glucose level control system determines that a carbohydrate treatment was initiated.
  • the glucose level control system enters a recovery mode, suspending both basal and correction doses until the return threshold duration 3316 is satisfied, which may be considered a maximum time duration in the recovery mode.
  • FIG. 1 The embodiment shown in FIG.
  • the return threshold duration 3316 may be satisfied to return the first mode without the glucose level 3404 reaching or rising above a return threshold level 3412 at GRT.
  • the banked time for satisfying the return threshold duration 3316 may have been reset to zero, reduced or temporarily suspended until rising above another threshold glucose level (and/or satisfying one or more of any other threshold criteria described herein). However, as shown, the glucose level 3404 did not dip below such a threshold glucose level, so no modification to the banked time occurred.
  • FIG. 27 shows another example glucose-time plot 3500 showing a reactivation threshold level 3512 (which may also be referred to as a recovery threshold glucose level in systems having reactivation mode, including as part of the recovery mode as discussed herein) that initiates a time for satisfying a return threshold duration 3520 (which may also be referred to as a minimum duration in, for example, the reactivation mode).
  • a reactivation threshold level 3512 which may also be referred to as a recovery threshold glucose level in systems having reactivation mode, including as part of the recovery mode as discussed herein
  • a return threshold duration 3520 which may also be referred to as a minimum duration in, for example, the reactivation mode.
  • the user inputs (e.g., received via the user interface controller 3108) corresponding to a user indication of a carbohydrate treatment or the system otherwise determines carbohydrate treatment as discussed herein, thus satisfying a hypoglycemic event criterion.
  • the hypoglycemic event criterion may additionally or alternatively be satisfied when the glucose level 3504 drops below the low glucose level 3508. Satisfying the hypoglycemic event criterion causes the system to enter recovery mode and, in the shown embodiment, triggering a suspension of basal and correction doses of regulatory medicament. Additionally or alternatively, this hypoglycemic event may trigger delivery of counter-regulatory medicament. At time treact the glucose level 3504 satisfies the reactivation threshold level 3512, causing the system to enter a reactivation mode where (in the embodiment shown) basal doses are resumed. As discussed herein, the basal doses may be ramped for the return threshold duration 3520 or less.
  • a time for satisfying the return threshold duration 3520 begins.
  • basal doses resume.
  • the return threshold duration 3520 is satisfied at time treturn, which causes the glucose level control system to resume the first mode and cause delivery of both basal and correction doses of regulatory medicament by the medicament pump.
  • FIG. 28 shows a flow diagram illustrating an example method 3600 that may be used by a glucose level control system (e.g., the glucose level control system 3100) to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after or when the subject experiences a hypoglycemic event.
  • the system can determine a glucose level of the subject at block 3604. This determination may be made based on a received measurement of the glucose level or by an estimation and/or prediction.
  • the system determines that the glucose level is equal to or greater than a first threshold glucose level. This determination may be based on the determined glucose level of the subject.
  • the system instructs a medicament pump to deliver basal doses and correction doses of medicament to the subject.
  • the system determines that at least one hypoglycemic event criterion is satisfied.
  • the at least one hypoglycemic event criterion may comprise a low glucose level. Additionally or alternatively, the at least one hypoglycemic event criterion may include any hypoglycemic event criterion described herein.
  • the system instructs the medicament pump to suspend delivery of at least one of the basal doses or the correction doses of medicament. Other doses of medicament, such as priming doses, may be suspended as well. This instruction may be based on the determination that the at least one hypoglycemic event criterion is satisfied.
  • the system determines that at least one reactivation criterion is satisfied.
  • the at least one reactivation criterion can include any reactivation criterion described herein, such as a reactivation threshold level and/or a reactivation threshold duration.
  • the system instructs the medicament pump to resume delivery of the at least one of the basal doses or the correction doses of medicament. This resumption of delivery may be based at least in part on the determination that the at least one reactivation criterion is satisfied. Other details that may be related to one or more of these steps are described herein.
  • FIG. 29 shows another flow diagram illustrating an example method 3700 that may be used by a glucose level control system (e.g., the glucose level control system 3100) to modify administration of glucose control therapy to a subject via an ambulatory medicament pump after or when the subject experiences a hypoglycemic event.
  • the system can determine a glucose level of the subject at block 3704.
  • the system instructs a medicament pump to deliver basal doses and correction doses of medicament to the subject.
  • the system determines that at least one hypoglycemic event criterion is satisfied, such as a hypoglycemic event criterion described herein.
  • the system instructs the medicament pump to suspend delivery of at least one of the basal doses and/or the correction doses of medicament.
  • the system determines that at least one reactivation criterion is satisfied, such as the reactivation criteria described herein (e.g., a reactivation threshold level, a reactivation threshold duration, a reactivation threshold glucose level rate of change).
  • the system instructs the medicament pump to resume delivery of the at least one of the basal doses and/or the correction doses of medicament. This resumption of delivery may be based at least in part on the determination that the at least one reactivation criterion is satisfied.
  • the system instructs the medicament pump to resume delivery of both basal dose and correction doses of medicament in response to determining that at least one return criterion is satisfied.
  • the at least one return criterion can include any reactivation criterion described herein, such as one or more return threshold levels, return threshold durations, and/or return threshold glucose level rates of change. Other details that may be related to one or more of these steps are described herein.
  • FIG. 30 shows a logical flow diagram illustrating an example method 3800 that may be used by a glucose level control system to enter a recovery mode and/or a reactivation mode after the subject experiences a hypoglycemic event.
  • the system can operate in a first mode at block 3804.
  • the first mode may include any features of the first mode or first intervention described herein, such as with FIG. 16 and/or FIG. 22.
  • the first mode may result in the glucose level control system generating a dose control signal configured to instruct at least basal doses, correction doses, and priming boluses of regulatory medicament to the subject.
  • the system determines that at least one hypoglycemic event criterion is satisfied, such as a hypoglycemic event criterion described herein.
  • the system may determine that the subject’s glucose level has dropped below a threshold low glucose level.
  • the threshold low glucose level may be, for example, about 60 mg/dl, about 65 mg/dl about 70 mg/dl, or some other value described herein.
  • the system in response to determining that the hypoglycemic event criterion is met, operates in a recovery mode. As a result of operating in the recovery mode, the glucose level control system may instruct the medicament pump to suspend delivery of both basal doses and correction doses of regulatory medicament to the subject. Other aspects of recovery mode described herein may be applicable.
  • Threshold criteria can include any threshold criteria described herein, such as reactivation criteria (e.g., fixed reactivation criteria, dynamic reactivation criteria) and/or return criteria (e.g., fixed return criteria, dynamic return criteria).
  • the threshold criteria include a reactivation threshold duration and at least two return threshold durations (e.g., a first return threshold duration determined from satisfaction of the hypoglycemic event criterion, a second return threshold duration determined from satisfaction of the reactivation criterion).
  • the system determines whether one or more threshold criteria are satisfied. If certain return criteria are satisfied as discussed herein, then the system operates again in the first mode at block 3804 (e.g., basal and correction doses resume).
  • the system determines at logic block 3824 whether one or more reactivation criteria are satisfied. If the system determines that certain reactivation criteria are not satisfied, then the system continues to operate in the recovery mode at block 3812. If the system determines that certain reactivation criteria are satisfied, then the system operates in a reactivation mode at block 3828 (e.g., basal doses resume and/or correction doses resume). The system continues to operate in reactivation mode at least until the system determines that threshold criteria are satisfied at logic block 3816. [0591] Thus, as shown in FIG.
  • the system may operate in the first mode and in recovery mode (e.g., if the certain threshold criteria that are satisfied are return criteria), or the system may operate in the first mode and the reactivation mode (e.g., if certain return criteria are not satisfied, but certain reactivation criteria are satisfied). For example, the system may operate in the first, recovery, and reactivation modes if certain reactivation criteria are satisfied before certain return criteria are satisfied. Other details that may be related to one or more of these steps are described herein.
  • the ambulatory medical device can be a portable or wearable device such as an ambulatory medicament pump (AMP) that provides life-saving treatment to a subject by delivering one or more medicaments (e.g., insulin and/or glucagon) to the subject.
  • AMP ambulatory medicament pump
  • an AMP can be an insulin pump or a bi -hormonal pump that controls a glucose level of a subject by infusing glucose and/or glucagon to the subject.
  • An AMP that provides glucose therapy to the subject may receive glucose level signals from a glucose sensor that indicate the glucose level of the subject and adjust the dose or frequency of the medicament delivery (e.g., insulin or glucagon) accordingly.
  • FIG. 31A illustrates a three-dimensional (3D) view of an example ambulatory medicament pump (AMP) 4000 comprising a housing 4002 with a wake button 4006 and a touchscreen display 4004.
  • FIG. 3 IB is an illustration of a cross sectional view of the AMP 4000 shown in FIG. 31 A.
  • all the electronic systems 4008 are included inside the housing 4002, for example, as a single integrated electronic board.
  • the wake button 4006 may be any type of button (e.g., capacitive, inductive, resistive, mechanical, etc.) that registers an input generated by user interaction with the wake button 4006 to generate a wake signal.
  • a wake signal may be a signal that activates a user interface of the AMP (e.g., a touchscreen display).
  • the wake button 4006, if touched, pressed, or held for a period, may generate the wake signal that activates the touchscreen display 4004.
  • touches on the touchscreen display 4004 are not registered until the wake button activates the touchscreen display.
  • the AMP remains locked from accepting at least certain types of user interaction or settings modification until a gesture (such as, for example, any of the gesture interactions described with reference to any of the embodiments disclosed herein) is received after the touchscreen display 4004 is activated by the wake button 4006.
  • a passcode may be required to unlock the touchscreen display.
  • the wake signal is generated by a sensor (e.g., a biometric sensor such as a fingerprint reader or a retinal scanner, an optical or RF proximity sensor, and the like).
  • the wake signal may be generated by user interaction with the touchscreen display 4004 or with an alphanumeric pad (not shown).
  • a wake signal may be generated based on facial recognition or other biometric indicia.
  • the wake signal may be generated by a wireless signal such as a signal generated by an RFID system or Bluetooth signals received from an electronic device or by detection of movement using one or more motion sensors such as an accelerometer.
  • the user may wake the AMP 4000 from a sleep state or unlock the AMP 4000 by, for example, interacting with the wake bottom.
  • the user interface may not receive any input from the user or any user input signals corresponding to user input.
  • Waking the AMP 4000 may include activating a touchscreen interface or presenting a lock screen to a user. Further, waking the AMP 4000 may include waking the touchscreen controller such that it can receive user input or user input signals corresponding to user input.
  • FIG. 32 illustrates different systems and sub-systems that may be included in an example glucose level control system (GLCS) 4100.
  • the GLCS 4100 may be a complete glucose level control system 200a or can include one or more components of a complete glucose level control system.
  • the GLCS 4100 may include systems and sub-systems that can enable monitoring a subject’s glucose level (e.g., glucose level), managing the subject’s diabetes, tracking a condition of the GLCS 4100, and/or communicating with one or more computing systems.
  • the GLCS 4100 may include a mono-hormonal or bi-hormonal medicament pump configured to administer one or more types of insulin and, in some cases, counter-regulatory agent (e.g., glucagon or other medicaments that can reduce or address hypoglycemia).
  • the GLCS 4100 may include one or more alarm generators, transceivers, touchscreen controllers, display controllers, encryption sub -systems, etc.
  • two or more of the systems may be integrated together inside a single housing 4002 (as shown in FIG. 31 A and 3 IB).
  • one or more systems or sub -systems may be individual modules contained in separate housings and communicate with other systems and/or the main unit via a wired or wireless communication link (e.g., Bluetooth).
  • the systems included in the GLCS 4100 may include a communication system 4120, a medicament delivery system 4112, a user interface system 4114, and a controller (or control system) 4102, which can be the same or similar in at least some respects to the other glucose level control system controllers described herein, including, for example, the controllers 202, 202a-c, and 400 described with reference to FIGS. 2A-D and 4A-B.
  • controller 4102 include one or features described with reference to one or more other controllers disclosed herein.
  • one or more systems may comprise one or more single purpose or multipurpose electronic sub systems.
  • One or more electronic sub-systems may perform procedures associated with different features of the GLCS 4100.
  • the systems or sub-systems may comprise a non- transitory memory that can store machine-readable instructions and a processor that executes the instructions 4108 stored in the memory.
  • the memory may be a non-volatile memory, such as flash memory, a hard disk, magnetic disk memory, optical disk memory, or any other type of non-volatile memory. Further, types of memory may include but are not limited to random access memory (“RAM”) and read-only memory (“ROM”).
  • RAM random access memory
  • ROM read-only memory
  • a system can be programed to perform different procedures each implemented based on a different set of instructions.
  • the medicament delivery system 4112 may be an external medicament delivery system that is in communication with the controller 4102 via the communication system 4120.
  • the controller 4102 may include one or more processors 4104, a memory 4110 that may comprise one or more non-transitory and/or non-volatile memories and an interface 4106 that enables data and signal communication between the controller 4102 and other systems of the GLCS (e.g., communication system 4120, medicament delivery system 4112, Glucose sensor interface 4122, or user interface system 4114).
  • the memory 4110 may be divided into two or more memory segments.
  • the memory 4110 may exchange data with sub-systems within the controller 4102 as well as other systems (e.g., via the interface 4106).
  • the memory 4110 may store data 4109 while the controller 4102 is powered or unpowered.
  • the processor 4104 may be any type of general-purpose central processing unit (“CPU”).
  • the controller may include more than one processor of any type including, but not limited to complex programmable logic devices (“CPLDs”), field programmable gate arrays (“FPGAs”), application-specific integrated circuits (“ASICs”) or the like.
  • the interface 4106 may include data transfer buses and electronic circuits configured to support data exchange among different sub-systems within the controller 4102. In some examples, in addition to data exchange between any of the systems and the controller 4102, the interface 4106 may support data and signal exchange among other systems of the GLCS 4100.
  • the controller may include more than one processor of any type including, but not limited to complex programmable logic devices (“CPLDs”), field programmable gate arrays (“FPGAs”), application-specific integrated circuits (“ASICs”) or the like.
  • the interface 4106 may include data transfer buses and electronic circuits configured to support data exchange among different sub-systems within the controller 4102. In some examples, in addition to data exchange between any of the systems and the controller 4102, the interface 4106 may support data and signal exchange among other systems of the
  • the interface 4106 may include a plurality of interconnected electronic modules for signal conditioning and signal conversion (e.g., A-to-D or ADC conversion and D-to-A conversion or DAC conversion) configured to support communication and data exchange between different systems.
  • the interface 4106 may convert an analog signal received from the communication system 4120 and convert it to a digital signal that can be processed by the controller 4102.
  • the interface 4106 may receive a digital control signal and convert it to a dose control signal (e.g., an analog signal) that can be transmitted to the medicament delivery system 4112, for example, to control one or more infusion pumps included in the medicament delivery system 4112.
  • a dose control signal e.g., an analog signal
  • the medicament delivery system 4112 may comprise one or more infusion pumps configured to deliver one or more medicaments (e.g., insulin or glucagon) from one or more medicament reservoirs (e.g., one or more medicament cartridges housed the medicament delivery system 4112) to a subject 4118.
  • the medicament delivery system 4112 may include electronic and mechanical components configured to control the infusion pumps based on the signals received from controller 4102 (e.g., via the interface 4106).
  • the medicament delivery system 4112 may include a pump controller that controls the infusion pumps upon receiving dose control signals from the controller 4102.
  • the user interface system 4114 may include a display to show various information about the GLCS 4100, for example, medicament type and delivery schedule, software status, and the like.
  • the display may show graphical images and text using any display technology including, but not limited to OLED, LCD, or e-ink.
  • the GLCS 4100 may include a user interface (e.g., an alphanumeric pad) that lets a user provide information or interact with the GLCS 4100 to modify the settings of the GLCS 4100, respond to request for certain actions (e.g., installing a software) and the like.
  • the alphanumeric pad may include a multitude of keys with numerical, alphabetical, and symbol characters.
  • the keys of the alphanumeric pad may be capacitive or mechanical.
  • the user may be a subject 4118 receiving medicament or therapy, or may be an authorized user, such as a clinician or healthcare provider, or a parent or guardian of the subject 4118.
  • the GLCS 4100 may include a touchscreen display that produces output and accepts input enabling a two-way interaction between the user and the GLCS 4100.
  • the touchscreen display may be any input surface that shows graphic images and text and registers the position of touches on the input surface.
  • the touchscreen display may accept input via capacitive touch, resistive touch, or other touch technology.
  • the input surface of the touchscreen display can register the position of touches on the surface. In some examples, the touchscreen display can register multiple touches at once.
  • the keypad may be a display of a keypad.
  • an alphanumeric pad comprising user-selectable letters, numbers, and symbols may be displayed on the touchscreen display.
  • the touchscreen may present one or more user-interface screens to a user enabling the user to modify one or more therapy settings of the ambulatory medicament device.
  • a user-interface screen may comprise one or more therapy change control elements (e.g., displayed on the touchscreen display) enabling a user or the subject to access therapy change controls and modify therapy settings by interacting with these control elements. For example, the user can modify the therapy settings by changing one or more control parameters using the corresponding therapy change control elements.
  • a therapy control parameter may be any parameter that controls or affects the volume, duration and/or the frequency of medicament doses delivered to the subject.
  • the communication system 4120 may include one or more wireless transceivers, one or more antennas, and one or more electronic systems (e.g., front end modules, antenna switch modules, digital signal processors, power amplifier modules, etc.) that support communication over one or more communication links and/or networks.
  • each transceiver may be configured to receive or transmit different types of signals based on different wireless standards via the antenna (e.g., an antenna chip).
  • Some transceivers may support communication using a low power wide area network (LPWAN) communication standard.
  • LPWAN low power wide area network
  • one or more transceivers may support communication with wide area networks (WANs) such as a cellular network transceiver that enables 3G, 4G, 4G-LTE, or 5G.
  • WANs wide area networks
  • one or more transceivers may support communication via a Narrowband Long-Term Evolution (NB-LTE), a Narrowband Internet- of-Things (NB-IoT), or a Long-Term Evolution Machine Type Communication (LTE-MTC) communication connection with the wireless wide area network.
  • NB-LTE Narrowband Long-Term Evolution
  • NB-IoT Narrowband Internet- of-Things
  • LTE-MTC Long-Term Evolution Machine Type Communication
  • one or more transceivers may support Wi-Fi® communication.
  • one or more transceivers may support data communication via Bluetooth or Bluetooth Low Energy (BLE).
  • BLE Bluetooth Low Energy
  • one or more transceivers may be capable of down-converting and up-converting a baseband or data signal from and to a wireless carrier signal.
  • the communication system 4120 may wirelessly exchange data between other components of the GLCS 4100 (e.g., glucose sensor 4116, or medicament delivery system 4112), a mobile device (e.g., smart phone, a laptop and the like), a Wi-Fi network, WLAN, a wireless router, a cellular tower, a Bluetooth device and the like.
  • the antenna may be capable of sending and receiving various types of wireless signals including, but not limited to, Bluetooth, LTE, or 3G.
  • the communication system 4120 may support direct end-to-end communication between the GLCS 4100 and a server or a cloud network.
  • the GLCS 4100 may communicate with an intermediary device (e.g., a smart phone or other mobile devices, a personal computer, a notebook, and the like).
  • the GLCS 4100 may include an eSIM card that stores information that may be used to identify and authenticate a mobile subscriber.
  • the eSIM card may enable the GLCS 4100 to function as an IoT device that can communicate over a network that supports communication with IoT devices.
  • the GLCS 4100 may be configured to transmit data using a narrowband communication protocol such as 2G or EDGE.
  • the GLCS 4100 may be paired with a mobile device at inception and permit real-time data access to the GLCS 4100 by a healthcare provider.
  • the GLCS 4100 may include a geolocation receiver or transceiver, such as a global positioning system (GPS) receiver.
  • GPS global positioning system
  • each of the GLCSs described herein may include one or more of the embodiments described with respect to the other GLCSs unless specifically stated otherwise.
  • the communication system 4120 may include a Near Field Communication (NFC) sub-system that enables contactless data exchange between the GLCS 4100 and an electronic device located in the vicinity of the GLCS 4100.
  • NFC Near Field Communication
  • the glucose sensor interface 4122 may be configured to receive glucose level signals (e.g., wireless signals) from a glucose sensor 4116.
  • the glucose sensor 4116 can be a wearable continuous glucose monitor (CGM) that is operatively connected to the subject 4118.
  • CGM wearable continuous glucose monitor
  • the glucose sensor 4116 may be attached to a site on subject’s body using adhesive patch holds and may include a cannula that penetrates the subject’s skin allowing the sensor to take glucose readings in interstitial fluid and generate glucose level signals that indicate the level of glucose in subject’s blood.
  • the GLCS 4100 may include one or more sensor interfaces configured to receive sensor signals (e.g., wireless sensor signals) from other types of sensors (e.g., heart bit sensor, temperature sensor, motion sensor, pressure sensor and the like).
  • sensor signals e.g., wireless sensor signals
  • the GLCS 4100 may receive sensor signals from a motion sensor indicating a movement of the subject 4118, via a motion sensor interface.
  • a sensor signal received from a motion sensor may be referred to herein as a “motion signal”.
  • the motion signals can be generated by a motion sensor connected to the subject 4118.
  • the motion sensor can be an accelerometer operationally connected to the subject 4118.
  • the accelerometer may detect and measure an acceleration of the subject 4118, generate a motion signal and transmit the motion signal to the motion sensor interface.
  • the GLCS 4100 may receive sensor signals from a pressure sensor connected to the subject near an infusion site where a cannula that delivers medicament from the GLCS 4100 to the subject through the skin of a subject.
  • the sensor signals received from such pressure sensor may indicate a level of pressure applied near or on the infusion site.
  • the GLCS 4100 may continuously, periodically (e.g., every 5 minutes, every 10 minutes, etc.), or intermittently receive glucose level signals from the glucose sensor 4116 via the glucose sensor interface 4122 (e.g., via a wired or a wireless data connection).
  • a glucose level signal may be an electronic signal indicative of a measured glucose level of the subject 4118.
  • the measured glucose level of associated with a glucose level signal may be correlated with a physiological glucose level of the subject.
  • the physiological glucose level of the subject can be a concentration of glucose in subject’s blood or an interstitial fluid in part of the subject’s body.
  • the measured glucose level of the subject may be a measured glucose level of the subject.
  • the measured glucose level of the subject may of be associated with a measured concentration of glucose in an interstitial fluid of a subject’s body.
  • the concentration of glucose in the interstitial fluid of the subject’s body may be correlated to the glucose level of the subject.
  • Measured glucose level may be referred to herein as “glucose level of the subject” or “glucose level”.
  • an amplitude of the glucose level signal may be proportional to or correlated to the glucose level of the subject.
  • a glucose level signal may carry glucose level data (e.g., measured glucose level values or information usable to determine glucose level values).
  • the glucose level signal, generated by the glucose sensor 4116 may comprise encoded glucose level data.
  • the glucose level signal may comprise glucose level data encoded onto a carrier signal, for example, using amplitude modulation, frequency modulation, and/or phase modulation.
  • the glucose level signal can be an analog signal encoded with digital data associated with the glucose level data.
  • the glucose level signal can be transmitted via a wireless link (e.g., a Bluetooth link, a Wi-Fi link, a cellular data link, and/or other wireless network infrastructure) and received by a wireless receiver included in the glucose sensor interface 4122. Subsequently, the glucose sensor interface 4122 may direct the glucose level signal to the controller 4102. In some examples, the controller 4102 may decode the glucose level data from the glucose level signal. In some embodiments, the glucose level data may be decoded by the glucose sensor interface 4122. In other embodiments, the glucose level signal sent by the sensor 4116 may be received by the communication system 4120 and transmitted to the controller 4102.
  • a wireless link e.g., a Bluetooth link, a Wi-Fi link, a cellular data link, and/or other wireless network infrastructure
  • the controller 4102 may determine a dose and a delivery time of a medicament (e.g., insulin or glucagon) based at least in part on the glucose levels of the subject 4118 decoded from the received glucose level signals. Subsequently, the controller 4102 may generate a dose control signal and transmit the dose control signal to the medicament delivery system 4112 of the GLCS 4100, to cause the delivery of the determined dose of medicament at the determined delivery time to the subject.
  • the controller 4102 may generate the dose control signal using a control algorithm.
  • the control algorithm may comprise a model - predictive control (MPC) algorithm and/or a basal control algorithm.
  • the dose of medicament may be a correction dose of medicament determined based on glucose level excursions indicated by the glucose level data.
  • the correction dose of medicament can include regulatory or counter -regulatory agents and may be generated using the MPC algorithm.
  • the basal dose can include regulatory agent and may be generated using a basal control algorithm.
  • one or more control algorithms executed by the controller 4102 may use glucose level of the subject 4118 and the value of one or more control parameters to determine dose and delivery times of a medicament to control the glucose level of the subject.
  • the controller 4102 may also determine a type of medicament (e.g., glucose or glucagon) based on the glucose level of the subject 4118.
  • the controller 4102 may use two or more sequential glucose levels associated with glucose level signals received at different times to determine the type, the dose and delivery time of a medicament that should be administered to the subject.
  • the controller 4102 may use glucose data received during a glucose measurement period to determine the type, the dose and the delivery time of a medicament that should be administered to the subject. Once the type, the dose and the delivery time of the medicament are determined, the controller 4102 may generate a corresponding dose control signal and transmit the dose control signal to the medicament delivery system 4112. Upon receiving the dose control signal, the medicament delivery system 4112 delivers the determined dose of the determined medicament at the determined delivery time, from a medicament reservoir to the subject 4118. In some examples, the dose control signal may be received by a pump controller of the medicament delivery system 4112 that controls the operation of the corresponding infusion pumps.
  • the GLCS 4100 may deliver multiple types of medicament therapies that are selectable by the user or automatically selected by the controller 4102.
  • the GLCS 4100 may deliver the therapy of infusing insulin into the subject 4118 and may also deliver glucagon into the subject 4118.
  • the user interface system 4114 may allow the subject 4118 or a user, to select the type of medicament infused to the subject 4118 during therapy (e.g., insulin, glucagon, or both).
  • the GLCS 4100 may deliver other hormones or medicaments to the subject.
  • the controller 4102 may determine the type of medicament that is delivered to the subject 4118 based at least in part on glucose levels associated with glucose level signals received from the sensor 4116.
  • the glucose sensor 4116 may generate a glucose level signal that does not correspond to a physiological glucose level of the subject 4118.
  • the glucose level values associated with such glucose level signal may be a glucose level artifact (herein referred to as “artifact”).
  • An artifact may be lower or higher than the physiological glucose level of the subject 4118.
  • the glucose level signal may indicate an artificially low glucose level.
  • a subject 4118 e.g., a body site where the cannula of the glucose sensor 4116 penetrates the subject’s skin
  • the glucose level signal may indicate an artificially low glucose level.
  • the subject 4118 when the subject 4118 is siting or sleeping, pressure may be applied on the glucose sensor 4116 or near the glucose sensor by subject’s body parts or an object (e.g., chair or bed) that supports the subject’s weight, resulting in erroneous glucose level signals that indicate artificially low glucose levels.
  • subject’s clothing may apply pressure on the glucose sensor 4116 and cause the generation of erroneous glucose level signals indicating artificially low glucose levels.
  • the controller 4102 may not maintain the glucose level of the subject 4118 within a desired or target range (e.g., a range set by one or more control parameters provided to the controller 4102).
  • the corresponding dose control signal generated based on the glucose level artifact associated with the glucose level signal, may result in delivery of a dose of insulin that is lower than a dose that would have been delivered based on a normal glucose level signal corresponding to the physiological glucose level of the subject; consequently, the infused insulin dose may not be sufficient to reduce the glucose level of the subject to a level within a target range for the subject 4118, resulting in hyperglycemia in the subject 4118.
  • the corresponding dose control signal may result in delivery of a dose of glucagon that is unnecessary or is higher than a dose that would have been delivered based on a normal glucose level signal; consequently, the infused glucagon dose may result in hypoglycemia in the subject 4118.
  • the controller 4102 may analyze the glucose levels decoded from glucose signals to identify artifacts. An artifact may be identified based on one or more sequentially or non-sequentially received glucose level signals. Once an artifact is identified, the controller 4102 may determine and generate the next dose control signal based at least in part on the identified artifact. In some cases, the controller 4102 may switch to an alternative control mode that implements one or more alternative control processes.
  • the alternative control processes can include, for example, changing a setting of the GLCS or switching a control algorithm to an offline mode of operation.
  • the controller can generate a dose control signal based on one or more isolated glucose measurements.
  • the controller 4102 may generate dose control signals based on one or more methods described in U.S. Patent No. 10,543,313, the contents of which are hereby incorporated by reference in its entirety herein.
  • the GLCS 4100 may notify the subject 4118 that the glucose sensor has generated glucose level signals that may not correspond to the physiological glucose level of the subject 4118 (e.g., using the user interface system 4114 and/or via a display).
  • the glucose sensor 4116 may generate artifacts (glucose level artifacts) that do not correspond to the physiological glucose level of the subject.
  • artifacts may be non-glucose related variations of the glucose level signal caused by, for example, pressure applied on the glucose sensor or near a location where the glucose sensor is connected to the subject 4118, variations of certain chemical species in subject’s blood or interstitial fluid, glucose sensor malfunctions (e.g., associated with glucose sensor 4116 hardware defects), local temperature changes, PH changes of a subject’s blood or interstitial fluid, keeping the glucose sensor on injection site for a long time and the like.
  • the GLCS 4100 may analyze the glucose level data decoded from glucose level signals to identify artifacts. In some examples, the GLCS 4100 may analyze the glucose levels after generating an initial dose control signal. In some other examples, the GLCS 4100 may analyze the glucose level data before generating a dose control signal. The GLCS 4100 may implement one or more methods to identify artifacts in the glucose level data. The GLCS 4100 may implement these methods by executing one or more artifact detection algorithms stored in a memory of the GLCS 4100 as machine readable instructions. For example, these instructions may be stored in the memory 4110 of the controller 4102 and executed by the processor 4104 of the controller 4102.
  • the controller 4102 may use one or more artifact management algorithms to generate dose control signals.
  • the artifact management algorithms may be part of the control algorithm used by the controller 4102 to generate medicament doses (e.g., correction doses or basal doses of medicament).
  • the artifact management algorithms may be executed by the controller 4102 when the controller 4102 operates the control algorithm in an artifact compensation mode.
  • the control algorithm When operated in the artifact compensation mode, the control algorithm may generate substitute dose control signals using artifact compensation processes.
  • transmitting a substitute dose control signal to the medicament delivery system 4112 may result in delivery of a substitute glucose control therapy to the subject in response to glucose level excursions.
  • the substitute glucose control therapy may be a glucose control therapy delivered in place of a glucose control therapy associated with glucose level data.
  • the substitute glucose control therapy may be a glucose control therapy delivered based on modified glucose level data (e.g., glucose data including modified glucose levels).
  • a substitute glucose control therapy may include delayed delivery of medicament, expedited delivery of medicament, or delivery of reduced or increased doses of medicament in response to glucose level excursions.
  • the substitute dose control signals may be generated when the GLCS 4100 is in an offline mode.
  • the substitute glucose control therapy may include suspending the glucose control therapy for a suspension period.
  • a substitute glucose control therapy may be a temporary glucose control therapy.
  • the substitute glucose control therapy may be delivered for a time period between identifying an artifact and receiving glucose data that does not include an artifact.
  • the artifact detection algorithms may be designed to identify artifacts, based on temporal variations of glucose levels decoded from glucose level signals received during a glucose measurement period (e.g., a period during which the glucose level signals are generated). Such artifacts may be identified based at least in part on a magnitude and/or a rate of change of the measured glucose level of the subject.
  • the controller 4102 may use: a time of day at which the corresponding glucose level signals were received, the performance of the wireless communication link between the glucose sensor 4116 and the glucose sensor interface 4122, glucose levels decoded from glucose level signals received prior to the glucose measurement period, amounts and delivery times of the one or more medicament therapies delivered prior to glucose measurement period, information associated with the subject (e.g., age, weight, medical history, and the like), history of glycemic control of the subject, subject’s schedule (e.g., a meal schedule, exercise schedule, or other activity schedules), or a prescription of the subject.
  • a time of day at which the corresponding glucose level signals were received the performance of the wireless communication link between the glucose sensor 4116 and the glucose sensor interface 4122
  • glucose levels decoded from glucose level signals received prior to the glucose measurement period amounts and delivery times of the one or more medicament therapies delivered prior to glucose measurement period
  • information associated with the subject e.g., age, weight, medical history, and the like
  • history of glycemic control of the subject
  • This information may be provided by a user (e.g., a guardian or a parent), the subject or a healthcare provider and may be stored in the GLCS 4100.
  • the controller 4102 may use other information and data received via a user interface of the GLCS 4100 or stored in a memory of the GLCS 4100 when executing an artifact detection algorithm to identify artifacts or suspected artifacts.
  • the GLCS 4100 may receive or update information usable for identifying artifacts, from a cloud server (e.g., a cloud server associated with a patient data network) via a wired or wireless data connection.
  • a cloud server e.g., a cloud server associated with a patient data network
  • FIG. 33A shows an example glucose level data 4200 representing glucose levels (block dots) of the subject 4118 decoded from one or more glucose level signals received from the glucose sensor 4116 (e.g., a series of glucose level signals sequentially received from the glucose sensor 4116).
  • the gray dashed line in FIG. 33A is the guide to the eye for visualizing the temporal behavior the subject’s glucose level.
  • the glucose sensor 4116 may generate the glucose level signals periodically at equal time intervals (e.g., every 2 minutes, every 5 minutes, every 10 minutes, etc.).
  • the glucose level signals may be generated at unequal time intervals.
  • the times at which the glucose level signals are generated may be determined and controlled by the controller 4102.
  • the glucose level data may include one or more artifacts or suspected artifacts.
  • artifacts may comprise glucose levels that are out of a normal glucose level range for the subject 4118 and additionally indicate a glucose level velocity (i.e., a rate of change of glucose level over time) larger than a threshold glucose level velocity, or a glucose level acceleration (i.e., a rate of change of glucose level velocity) that is larger than a threshold glucose level acceleration for the subject 4118.
  • the normal glucose level range, the threshold glucose level velocity, or the threshold glucose level acceleration for the subject 4118 may be provided by a healthcare provider and stored in a memory of GLCS 4100.
  • the one or more artifact detection algorithms may be used by the controller 4102 to identify artifacts based on different methods and based on different subsets of glucose levels associated with a glucose measurement period.
  • the controller 4102 may determine an artifact time window 4202 during which the one or more glucose levels associated with the artifacts are received.
  • the time interval between a first time tl 4201 and a second time t2 4203 may be selected as an artifact time window.
  • the controller 4102 may identify artifacts in the glucose level data (e.g., glucose level data 4200), by first determining an artifact time window (e.g., for example, a window similar to the artifact time window 4202 shown in FIG. 33A) based on detecting one or more outlier glucose levels and/or outlier glucose level variations (e.g., glucose level velocity or acceleration) in the glucose level data.
  • an artifact time window e.g., for example, a window similar to the artifact time window 4202 shown in FIG. 33A
  • outlier glucose level may be associated with glucose levels above or below a typical glucose level range, or a typical temporal behavior of the glucose levels.
  • the glucose level 4208 may be identified as an outlier glucose level because it is larger or greater than a maximum glucose level 4210 determined for the artifact time window 4202 and/or because it is associated with a glucose level velocity (e.g., measured with respect to glucose level 4214 and/or glucose level 4204) that may be larger than a maximum glucose level velocity.
  • the glucose level 4204 may be identified as an outlier glucose level because it is smaller or less than a minimum glucose level 4206 determined for the artifact time window 4202 and/or because it is associated with a glucose level velocity (e.g., measured with respect to glucose level 4212) that may be larger than a maximum glucose level velocity.
  • the artifact time window 4202 may be a time period during which the glucose level signals associated with the outlier glucose levels and/or outlier glucose level variations are received.
  • the artifact time window 4202 can be a fixed period, a fixed number of measurement intervals, a dynamic period, or a dynamic number of measurement intervals.
  • the duration of the artifact time window 4202 can correspond to a pre- prandial, prandial, or post-prandial period, a diurnal period when a subject is sleeping or expected to be sleeping, another diurnal period, a period related to an observed or estimated deviation in glucose level data, and/or other factors that influence the stability of the glucose level of the subject.
  • the controller 4102 may use the glucose levels received during the artifact time window 4202 to generate filtered glucose level data.
  • the filtered glucose level data may be generated by averaging over the glucose levels received during the artifact time window 4202.
  • the filtered glucose level data may be generated by eliminating the outlier glucose levels and/or outlier glucose level variations and averaging over the remaining glucose levels.
  • the filtered glucose level data may be generated by calculating a Fourier transform of the glucose levels received during the artifact time window 4202 and filtering the resulting frequency domain data (e.g., eliminating glucose levels associated with frequencies above a threshold frequency).
  • the filtered glucose level data may be projected glucose level data.
  • the projected glucose level data may be generated based at least in part on the glucose levels associated with the glucose level signals received prior to the artifact time window 4202, a history of a subject’s glycemic control (e.g., stored in the memory 4110) of the controller 4102, and/or one or more medicament therapies delivered prior to the artifact time window 4202 (e.g., medicament types, medicament doses and delivery times associated with the delivered therapies).
  • the controller 4102 may compare each of the glucose levels included in the artifact time window 4202 with the filtered glucose level data to obtain residual values (e.g., by calculating a difference between the magnitudes of the glucose levels in the glucose level data and filtered glucose level data). Subsequently, the controller 4102, may identify the artifacts by determining that an absolute value of one or more residual values are larger than a threshold residual value. In some cases, the controller 4102 may determine that an outlier glucose level is an artifact based on the corresponding residual value.
  • the controller 4102 may determine that a portion of the glucose level data received during the artifact time window 4202 is unreliable and should not be used to generate a dose control signal, based at least in part on a number of residual values that are larger than the threshold residual value.
  • the controller 4102 may identify artifacts in the glucose level data (e.g., glucose level data 4200), by determining a spectral content of glucose level data (e.g., by calculating a Fourier transform of the glucose level data). The controller may first determine an artifact time window and then determine a spectral content of a portion of glucose data received during the artifact time window. Up on determining the spectral content of the glucose level data or the portion of the glucose level data, the controller 4102 may determine whether an amplitude of one or more spectral components of the spectral content exceeds a threshold amplitude and identify the corresponding glucose levels as artifacts.
  • the controller 4102 may identify artifacts in the glucose level data (e.g., glucose level data 4200), by determining a spectral content of glucose level data (e.g., by calculating a Fourier transform of the glucose level data). The controller may first determine an artifact time window and then determine a spectral content of a portion of glucose data
  • the controller 4102 may identify artifacts in the glucose level data (e.g., glucose level data 4200), by calculating one or more statistical characteristics of the glucose level data (e.g., entropy, variance, and the like) and determining that at least one calculated statistical characteristic is indicative of the presence of one or more artifacts in the glucose level data.
  • the controller 4102 may use statistical methods to identify one or more frequently occurring glucose level variation patterns for the subject 4118 using glucose level signals received during one or more preceding glucose measurement periods. These subject specific glucose variation patterns may be stored in a memory of the GLCS 4100 and used for identifying artifacts in a subsequent glucose level data received from the glucose sensor 4116.
  • the controller 4102 may density the corresponding glucose levels as artifact. In some cases, if one or more glucose level variation patterns identified in the subsequent glucose level data do not match with the stored subject glucose level variation patterns, the controller 4102 may further analyze the subsequent glucose level data using other artifact identification methods (including, e.g., the methods described herein).
  • the controller 4102 may identify a glucose level, decoded from a glucose level signal, as an artifact based on a value of the glucose level, or based on a rate of change associated with the glucose level determined using the glucose level and one or more glucose levels received before receiving the glucose level. For example, the controller 4102 may identify an artifact based on a last glucose level signal received from the glucose sensor 4116 and two or more glucose level signals received before the last glucose level signal and stored in a memory of the GLCS 4100 (e.g., a memory 4110 of the controller 4102). In some examples, the glucose level signal and the one or more glucose level signals received before the last glucose level signal, may be consecutive glucose level signals generated by the glucose sensor 4116.
  • an artifact may be identified by analyzing the last glucose level signal and two or more of the glucose level signals received, at 1:55, 1:50, 1:45, 1:40, and/or 1:35 pm stored in the memory 4110.
  • the controller 4102 may identify the glucose level as an artifact or suspected artifact.
  • the glucose level 4208 may be identified as a suspected artifact because it is larger than a maximum glucose level 4210.
  • the glucose level 4204 may be identified as a suspected artifact because it is smaller than a minimum glucose level 4206.
  • Such suspected artifacts may be identified as artifact if they also indicate a temporal glucose level variation associated with artifacts.
  • the minimum and maximum glucose levels 4206/4210 can be different than target minimum glucose levels and a target maximum glucose levels used by the control algorithm of the GLCS 4100 to generate dose control signals and maintain the glucose level of the subject within a safe range (e.g., below the target maximum glucose level and above the minimum target glucose level).
  • the maximum glucose level 4210 or the minimum glucose level 4206 may be values stored in a memory of the GLCS 4100.
  • the minimum and maximum glucose levels 4206/4210 may be reference values provided by a user, the subject, manufacturer, or a healthcare provider and saved in the memory.
  • the minimum and maximum glucose levels 4206/4210 may be determined by the controller 4102 based on glucose level signals measured during one or more preceding glucose measurement periods.
  • a plurality of the maximum and minimum glucose levels may be stored in the GLCS 4100 corresponding to different times of the day at which the glucose level signals are received. For example, the maximum glucose level for a subject may be higher during mealtime and the minimum glucose level for a subject may be lower during an exercise time. Accordingly, the controller 4102 may select different minimum/maximum glucose levels to avoid identifying one or more glucose levels that are low or high due to an activity, as artifacts.
  • the controller 4102 may determine or modify the maximum or minimum glucose levels 4206/4210 based at least in part on one or more medicament deliveries prior to receiving the glucose level signals that are analyzed to identify artifacts. For example, the controller 4102 may use a medicament type, a delivery time and a medicament dose associated with a preceding medicament delivery (e.g., the last medicament delivery before receiving the glucose level data) to estimate the maximum glucose level (e.g., if the last medicament was glucagon) or a minimum glucose level (e.g., if the last medicament was insulin). The medicament type, a delivery time and a medicament dose associated of a preceding medicament delivery may be decoded from the corresponding dose control signal.
  • a medicament type, a delivery time and a medicament dose associated of a preceding medicament delivery may be decoded from the corresponding dose control signal.
  • the maximum glucose level can be greater than or equal to 450 mg/dL, greater than or equal to 400 mg/dL, or greater than or equal to 350 mg/dL) and minimum glucose level can be between 30 to 40 mg/dL, 40 to 50 mg/dL, or 50 to 60 mg/dL.
  • the controller 4102 may identify an artifact by calculating a glucose level drop based on the last received glucose level signal and the glucose level signal received before the last glucose level signal. In some cases, the controller 4102 may calculate a glucose level drop based on a difference between glucose levels associated with two glucose level signals received during a glucose level measurement period or an artifact time window. The glucose level drop may be compared to a threshold glucose drop to determine whether the calculated glucose level drop exceeds the threshold glucose level drop. In some cases, the threshold glucose level drop may be a reference value provided by a user, the subject, manufacturer, or healthcare provider and saved in a memory of the GLCS 4100.
  • the threshold glucose level drop may be determined by the controller 4102 based at least in part, a time of the day when the one or more glucose level signals are received, a type, dose and delivery time of the last medicament delivery to the subject 4118, or glucose levels of the subject measured during one or more measurement periods before receiving the one or more glucose level signals.
  • the controller 4102 may identify an artifact based on a velocity of a subject’s glucose level (herein referred to as “glucose level velocity” or “rate of change of glucose level”).
  • a glucose level velocity may be a rate of change of glucose level determined at a certain time, or over a time period.
  • the controller 4102 may identify an artifact or suspected artifact by calculating one or more velocities based on two or more glucose levels.
  • the glucose level velocity may be an absolute value of a rate of change of a subject’s sugar level.
  • a glucose level velocity can be a glucose level drop velocity or a glucose level jump velocity.
  • the controller 4102 may calculate the glucose level velocity based on the two glucose level signals received at different times (for example, the last two glucose signals received).
  • the glucose level velocity may be calculated by: 1) calculating a glucose level difference between the glucose level decoded from the two glucose level signals (for example glucose levels 4212 and 4204, or glucose level 4214 and glucose level 4208 in the glucose level data 4200), or 2) dividing a glucose level difference by a time difference between the times at which these glucose levels are received.
  • the controller 4102 may calculate an average glucose level velocity by calculating a plurality of velocities based on a plurality of glucose level signal pairs and calculate the average glucose level velocity by dividing a sum of the plurality of signal level pairs by a number of glucose level signal pairs.
  • FIG. 33B shows an example of glucose level data 4220 representing a series of glucose levels of a subject associated with glucose level signals received from a glucose sensor 4116 over a period (the gray dashed line is the guide to the eye for visualizing the temporal behavior).
  • the slope of the solid line indicates a threshold glucose level velocity 4229 (threshold rate of change of glucose level) above which the variation of the glucose level is considered anomalous and the corresponding glucose level are identified as artifacts.
  • the threshold glucose level velocity may be referred to herein as “threshold velocity”.
  • the controller 4102 may identify the glucose levels associated with any of the glucose levels 4222, 4224, 4226, and 4228 as an artifact because the calculated glucose level velocity using each of these glucose levels and the glucose level preceding that glucose level, is larger than the threshold velocity 4229.
  • the calculated glucose level velocity using glucose level 4224 and glucose level 4222 is larger than the threshold velocity (the slope of the solid line 4229).
  • the glucose level velocity associated with the glucose levels 4226 and 4224 exceeds the threshold velocity 4229.
  • the controller 4102 may compare the glucose level velocity to a threshold velocity to determine whether the calculated glucose level velocity exceeds the threshold velocity. For example, if the calculated glucose level velocity exceeds the threshold velocity, a glucose levels used to calculate the glucose level velocity (e.g., the glucose level associated with the last received glucose level signal) may be identified as an artifact.
  • a threshold velocity may be a drop threshold velocity associated with a decrease of the glucose level or a jump threshold velocity associated with an increase of the glucose level as indicated by glucose level signals received from the glucose sensor.
  • the threshold velocity may be stored in a memory of the GLCS 4100.
  • the threshold velocity may be a reference value provided by a user, the subject, a manufacturer a healthcare provider and saved in the memory. In some cases, the threshold velocity may be determined by the controller 4102 based on glucose level velocities measured during one or more previous glucose measurement periods. In some cases, a threshold velocity may be associated with a time of the day at which the glucose level signal is received. For example, the jump threshold velocity may be higher during a mealtime and the drop threshold velocity may be higher during an exercise period.
  • the controller 4102 may select and use different threshold velocities (e.g., different drop threshold velocities or jump threshold velocities) when searching for artifacts in glucose data to avoid identifying a velocity that is high or low due to subject’s activity, as an artifact.
  • the drop threshold rate of change may be greater than or equal to a maximum glucose level drop rate of change.
  • a maximum glucose level drop velocity may be 2 mg/dL/min, 3 mg/dL/min, 4 mg/dL/min, 5 mg/dL/min, 6 mg/dL/min or any value greater than or between any two of the foregoing values.
  • the controller 4102 may identify a threshold velocity based at least in part on one or more medicament deliveries prior to receiving the glucose level data that is analyzed to identify artifacts.
  • the controller 4102 may use a medicament type, a delivery time and/or a medicament dose of the last medicament delivery (e.g., based on the corresponding dose control signal), to estimate a drop threshold velocity (e.g., if the last medicament was glucagon) or a jump threshold glucose level jump velocity (e.g., if the last medicament was insulin).
  • the controller 4102 may set the threshold glucose level velocity to be 6 mg/dL/min, or 7 mg/dL/min when analyzing the glucose level signals received during the measurement period.
  • the controller may set the threshold glucose level velocity to be a value lower than the medicament bolus threshold glucose level velocity, such as, for example, 2 mg/dL/min, or 3 mg/dL/min.
  • the controller 4102 may identify an artifact based on an acceleration of the subject’s glucose level associated with the glucose level data that is analyzed for identifying artifacts.
  • the acceleration of a subject’s glucose level (herein referred to as “glucose level acceleration,” “rate of change in the glucose level velocity,” or “rate of change in the glucose level rate of change”) may be a rate of change of a rate of change of glucose level (a rate of change of glucose level velocity).
  • glucose level acceleration may be calculated based on the last glucose level signal received and two or more preceding glucose level signals received within an acceleration calculation time window. For example, when the measurement interval of the glucose sensor is 5 minutes, the acceleration calculation time can encompass glucose levels received over 10 - 120 minutes prior to the time of the most recent glucose level signal.
  • an acceleration of a subject’s glucose level may be calculated based on the glucose levels associated with the last glucose level signal, a first glucose level signal received immediately before the last glucose level signal and a second glucose level signal received immediately before the first glucose level signal.
  • the calculated glucose level acceleration may be compared to a threshold glucose level acceleration (e.g., a threshold rate of change of rate change of the rate of change of the glucose level) to determine whether the calculated glucose level acceleration exceeds the threshold glucose level acceleration. If the glucose level acceleration exceeds the threshold glucose level acceleration, the controller 4102 may identify the glucose levels used to calculate the glucose level acceleration as artifacts.
  • the threshold glucose level acceleration may be referred to herein as “threshold acceleration”.
  • the glucose level acceleration may be calculated by 1) calculating a velocity difference between a first glucose level velocity, calculated using the glucose level associated with the last glucose level signal and a first glucose level signal, and a second glucose level velocity, calculated using the glucose level associated with the first glucose level signal and a second glucose level signal, 2) dividing the velocity difference by the difference between the times at which the last glucose level signal and the second glucose level signals are received.
  • the threshold acceleration may be stored in a memory of the GLCS 4100. In some cases, the threshold acceleration may be a reference value, provided by the subject, a user (e.g., a parent or a guardian), a manufacturer or a healthcare provider via a user interface of the GLCS 4100.
  • the controller 4102 may determine the threshold glucose level acceleration based on the glucose levels of the subject associated with preceding glucose level signals (e.g., glucose level signals received before the glucose level signals from which the glucose level data has been decoded). In some cases, a plurality of threshold accelerations may be stored in the GLCS 4100 corresponding to different times of the day at which the glucose level signal is received. The controller 4102 may determine a time of the day during which the glucose level data is analyzed and select the corresponding threshold glucose level acceleration from the stored values of the threshold acceleration. [0638] FIG.
  • a glucose level trace 4240 comprising glucose levels (black dots) representing a series of glucose levels of a subject associated with glucose level signals received from a glucose sensor 4116 over a measurement time period (the gray dashed line is the guide to the eye for visualizing the temporal behavior).
  • the controller 4102 may calculate a glucose level acceleration using the last glucose level 4248 and at least the glucose levels 4246 and 4244 received immediately before the last glucose level 4248. The controller 4102 may determine that the last glucose level 4248, or the last three glucose levels 4248, 4246 and 4244, are artifacts if the calculated glucose level acceleration exceeds a threshold acceleration.
  • a first glucose level acceleration may be calculated using the last glucose level 4248 and glucose levels 4246 and 4244
  • a second acceleration may be calculated using the glucose level 4246 and the glucose levels 4244 and 4242.
  • the controller 4102 may calculate the average of the first and the second glucose level accelerations with the threshold acceleration to determine whether the corresponding glucose levels are artifacts. [0639] In some cases, the controller 4102 may identify an artifact based on a calculated velocity and a calculated acceleration of the subject’s measured glucose level, for example, calculated using three or more consecutive glucose level signals received from the glucose sensor 4116.
  • the controller may identify the last glucose level or the last three glucose levels as artifacts even if the none of the calculated glucose velocities exceed the threshold glucose level velocity.
  • the controller 4102 may receive the values for a threshold acceleration, a threshold velocity, a threshold glucose level drop, a maximum glucose level, or a minimum glucose levels from a computing device (e.g., the computing device of a healthcare provider or a manufacturer) via a wireless data connection (e.g., a direct end-to- end data link, an LTE connection).
  • a computing device e.g., the computing device of a healthcare provider or a manufacturer
  • a wireless data connection e.g., a direct end-to- end data link, an LTE connection.
  • the computing device can be an intermediary device in communication with GLCS 4100 and an electronic device of a healthcare provider or a manufacturer.
  • the controller 4102 may determine whether a time of the day during which glucose level data is analyzed overlaps with a time period during which the subject may not have any activity (e.g., a sleeping time period). In these implementations, the controller 4102 may identify a glucose level drop, or a low measured glucose level over an extended period, as an artifact associated with a constant pressure applied on the glucose sensor 4116 or in the vicinity of the glucose sensor 4116 when subject is resting or sleeping.
  • the controller 4102 may determine the threshold velocity, threshold acceleration, threshold glucose level drop, maximum glucose level or minimum glucose level, based at least in part on the determination that the subject is not moving.
  • the controller 4102 may receive motion signals from one or more motion sensors connected to the subject and in communication with the GLCS 4100 (e.g., via a wireless connection) and determine that the subject 4118 is resting or sleeping based on the motion signals (e.g., when motion signals indicate that the subject is not moving).
  • the controller 4102 may determine that the subject 4118 is moving and therefore a low glucose level measured over an extended period may not indicate that the corresponding glucose level signals are artifacts associated with pressure applied on the glucose sensor 4116. In such cases, the controller 4102 may further analysis the suspected artifacts using other methods and/or criteria.
  • the controller 4102 may use one or more sensor signals received from a temperature sensor or heart rate sensor to determine whether the subject is moving or not.
  • the controller 4102 may compare the corresponding glucose level variations with the glucose level variations previously recorded by the GLCS 4100 to determine whether similar variations have been previously measured. In some cases, if the GLCS 4100 determines that similar glucose level variations have been previously recorded for extended periods, the GLCS 4100 may ignore the corresponding artifact and generate a dose control signal based on the one or more glucose level signals received.
  • the GLCS 4100 may use machine-learning algorithms or other algorithms to identify subject specific patterns in the glucose level variations measured during one or more measurement periods (e.g., preceding measurement periods); subsequently the controller 4102 may use the subject specific patterns to distinguish artifacts from variations associated with subject’s glucose level.
  • the controller 4102 may determine threshold values (e.g. threshold accelerations, threshold glucose level drops, threshold velocities), maximum glucose level or minimum glucose level, based on glycemic control characteristics of a subject recorded over a longer period of time (e.g., days, weeks, or months). In such cases, the controller 4102 may use various algorithms (e.g., machine learning algorithms) to determine threshold values and the maximum/minimum glucose levels for the subject 4118.
  • threshold values e.g. threshold accelerations, threshold glucose level drops, threshold velocities
  • maximum glucose level or minimum glucose level based on glycemic control characteristics of a subject recorded over a longer period of time (e.g., days, weeks, or months).
  • the controller 4102 may use various algorithms (e.g., machine learning algorithms) to determine threshold values and the maximum/minimum glucose levels for the subject 4118.
  • one or more artifacts may be artificially low glucose levels or artificially high glucose levels.
  • an artificially low glucose level can be a glucose level lower than a low glucose level limit.
  • an artificially high glucose level can be a glucose level signal associated with glucose level larger than a high glucose level limit.
  • the controller 4102 when the controller 4102 identifies an artifact, it may determine whether the artifact is an artificially low glucose level or an artificially high glucose level.
  • the low and high glucose level limits may be subject specific reference values stored in a memory of the GLCS 4100 or determined by the controller 4102 of the GLCS 4100.
  • the high glucose level limit may be the maximum glucose level and the low glucose level limit may be the minimum glucose level used to identify artifacts.
  • the controller 4102 may analyze the glucose level signals received from the glucose sensor 4116 to identify or detect suspected artifacts (e.g., outlier glucose levels). In some cases, the controller 4102 may perform further analysis to determine whether the suspected artifacts are artifacts (e.g., glucose level that are not indicative of a physiological glucose level of the subject 4118).
  • suspected artifacts e.g., outlier glucose levels
  • the controller 4102 may perform further analysis to determine whether the suspected artifacts are artifacts (e.g., glucose level that are not indicative of a physiological glucose level of the subject 4118).
  • the controller 4102 may identify one or more artifacts based at least in part on the one or more sensor signals received from one or more sensors (e.g., motion sensor, pressure sensor, heart rate sensor and the like). For example, the controller 4102 may receive a sensor signal from a pressure sensor connected to the glucose sensor and/or the subject indicating that pressure is applied on the glucose sensor or a region near the glucose sensor (e.g., a region on subject’s skin). If such sensor signal coincides with reception of a glucose level signal indicating a low glucose level, the controller 4102 may identify the low glucose level as an artifact (e.g., an artificially low glucose level).
  • an artifact e.g., an artificially low glucose level
  • the controller 4102 may identify one or more artifacts based on a first glucose level data received from a first glucose sensor during a first time period and a second glucose level data received from a second glucose sensor during a second time period.
  • the first glucose sensor and the second glucose sensor may be connected to different regions of the subject’s body (e.g., regions on subject’s skin).
  • the first and the second time periods may be identical.
  • the first and the second time periods may be non-overlapping or partially overlapping time periods.
  • the controller 4102 may identify the artifacts based on a comparison between the first and the second glucose level data.
  • the controller 4102 of the GLCS 4100 may identify artifacts in the glucose level data based at least in part on amplitude or strength of corresponding glucose level signals (e.g., used to decode the glucose levels data), or glucose level signals received during the corresponding measurement time period or artifact time window.
  • the corresponding glucose level signals or the glucose level signals may be wireless signals (e.g., Bluetooth signals) received by the glucose sensor interface 4122, and the controller 4102 may determine the strength of the wireless signals based on the information received from the glucose sensor interface 4122.
  • the corresponding glucose level signals or the glucose level signals are weaker than a set value (e.g., a normal glucose level signal strength/amplitude or glucose level signal amplitude range saved in the memory 4110 of the controller 4102), the glucose levels decoded from the corresponding glucose level signals or the glucose level signals may be identified as artifacts. In some cases, other characteristics of the corresponding glucose level signals or the glucose level signals (e.g., temporal variation and signal -to-noise ratio) may be used by the controller 4102 to identify artifacts.
  • the controller 4102 may determine whether one or more suspected artifacts detected during a glucose measurement period are correlated with the weakness of the wireless glucose level signals received during the glucose measurement period or an artifact time window. For example, if the wireless glucose level signals are weakened due to subject’s body position or (e.g., when a body part blocks wireless signal pathways between the glucose sensor 4116 and the glucose sensor interface 4122), it is possible that pressure is applied on or around an area where the glucose sensor 4116 is connected to the subject’s body.
  • the controller 4102 may identify the suspected artifacts as artifacts associated with pressure applied on or near the glucose sensor 4116.
  • the controller 4102 may identify an artifact, based on the strength of the corresponding wireless glucose level signal. For example, a glucose level decoded from a glucose level signal received during a time period when the wireless glucose level signals are weakened may be identified as an artifact (or suspected artifact).
  • the controller 4102 of the GLCS 4100 may operate the control algorithm in an artifact compensation mode to generate dose control signals to maintain the glucose level of the subject 4118 within a set range (e.g., a normal glucose level range associated with the subject).
  • the dose control signals generated in the control algorithm in the artifact compensation mode may reduce the risk of hyperglycemia or hypoglycemia that may occur if the medicament dose and/or medicament delivery time are determined based glucose level data that contains the artifacts.
  • the control algorithm may generate the dose control signal using one or more of artifact compensation processes including: delaying, reducing, expediting, increasing, or reducing doses of medicament in response to glucose level excursions associated with the glucose level data that contains the artifacts.
  • delaying or expediting a dose of medicament may include delaying or expediting the dose of medicament relative to a medicament delivery time associated with the glucose level data that contains the identified artifacts.
  • increasing or reducing a medicament dose may include increasing or reducing the medicament dose relative to a medicament dose associated with the glucose level data that contains the identified artifacts.
  • the controller 4102 may reduce or delay the delivery of a dose of a counter regulatory medicament (e.g., glucagon), increase a dose of insulin, or deliver a dose of insulin early.
  • a counter regulatory medicament e.g., glucagon
  • the controller 4102 may increase the delivery of a counter regulatory medicament (e.g., glucagon), deliver a dose of glucagon early, decrease a dose of insulin, or deliver delay a delivery of insulin.
  • the controller 4102 may temporarily increase or reduce medicament doses until glucose data associated with a threshold number of glucose levels received after identifying the artifacts, is free of artifacts.
  • the threshold number of glucose levels may be provided by a manufacturer, healthcare provider, the user, or the subject.
  • delaying medicament delivery to the subject may comprise suspending the medicament delivery for a suspension period.
  • an artifact compensation process may comprise receiving glucose level signals from a second glucose sensor different from the glucose sensor that generated the glucose level data in which an artifact is identified.
  • the corresponding control algorithm may generate the dose control signal based at least in part on second glucose level data decoded from the glucose level signals from a second glucose sensor.
  • control algorithm may include one or more artifact management algorithms that may be executed when the control algorithm is operated in an artifact compensation mode.
  • the artifact management algorithms may comprise one or more artifact compensation processes described herein.
  • an artifact compensation process may operate the control algorithm in an offline mode of operation and generate the dose control signal without using the glucose level data.
  • the controller may generate dose control signals based on methods described in U.S. Patent No. 10,543,313, the contents of which are hereby incorporated by reference in its entirety herein.
  • an artifact compensation process may generate the dose control signal using modified glucose level data generated by the controller 4102.
  • the modified glucose level data may comprise modified glucose levels different from the glucose levels associated the glucose level data that contains the artifacts.
  • the controller 4102 may first generate an initial dose control signal based on glucose levels decoded from glucose level signals received from the glucose sensor 4116, and if an artifact is identified in the glucose levels, the controller 4102 may modify the initial dose control signal based at least in part on the identified artifact. Subsequently the controller 4102 may transmit the modified dose control signal to the medicament delivery system 4112.
  • the controller 4102 may first analyze one or more glucose levels decoded from glucose level signals received from the glucose sensor 4116 to identify artifacts and then generate a dose control signal. In these examples, if an artifact is identified in the glucose levels, the controller 4102 may generate the dose control signal based at least in part on the identified artifact and using an artifact management algorithm. In some cases, upon identifying an artifact, the controller 4102 may switch to an offline operational mode. In some such cases, in the offline operational mode the controller 4102 may generate a dose control signal based on isolated glucose measurements.
  • the controller 4102 may restrict calibration of the glucose sensor 4116. For example, when an artifact is detected, the GLCS 4100 may lock a user interface associated with sensor calibration and inform the subject 4118 that due to detection of an artifact, glucose sensor calibration is temporary unavailable (e.g., via a user interface such as a touchscreen display).
  • the GLCS 4100 may switch to an offline operation mode and notify the subject (or a user) that due detection of artifacts the GLCS 4100 is switched to an offline mode.
  • the GLCS 4100 may request the user to provide isolated glucose measurements via a user interface (e.g., a touchscreen display) and use the isolated glucose measurements provided by the subject (or the user) to generate dose control signals.
  • the GLCS 4100 may operate the control algorithm in an artifact compensation mode to delay the delivery of medicament with respect to a delivery time associated with the artifacts or the glucose level data that contains the artifacts.
  • the artifact compensation process may generate a dose control signal that results in delayed delivery of medicament in response to glucose level excursions associated with the glucose level data that contains the artifacts.
  • the GLCS 4100 may delay the delivery of medicament until receiving one or more additional glucose level signals.
  • the controller 4102 may cause the glucose sensor 4116 to generate and transmit additional glucose level signals (in addition to periodically generated glucose level signals transmitted to the GLCS 4100).
  • the controller may send an electronic request to the glucose sensor 4116 and in response to the electronic request, the glucose sensor 4116 may generate and transmit the additional glucose level signal.
  • the additional glucose level signals may be received from a second glucose sensor different from the glucose sensor 4116 that generated the one or more glucose levels or the glucose level data.
  • the first and the second glucose sensors may be connected to different regions of the subject’s body.
  • the controller 4102 may analyze the one or more additional glucose level signals and if one or more glucose levels or glucose level variations associated with the additional glucose level signals are identified as artifact, the controller 4102 may switch the GLCS 4100 to an offline mode where GLCS 4100 delivers glucose therapy to the subject without using glucose level signals received from the first or the second glucose sensors. In some cases, if the controller 4102 does not identify any artifact in the glucose level data received from the second glucose sensor, it may generate a dose control signal based on the glucose level data received from the second glucose sensor.
  • the controller 4102 may send a user notification to a user interface (e.g., a user interface of the GLCS 4100) requesting a measured glucose level value to be provided via the user interface.
  • a user interface e.g., a user interface of the GLCS 4100
  • the GLCS 4100 may display a message on a touchscreen display indicating that an artifact has been detected and in order to proceed with the glucose level therapy, a measured glucose level has to be provided via the touchscreen display.
  • a measured glucose level may be a glucose level measured by another glucose sensor that is connected to the subject but that is not in communication with the GLCS 4100.
  • a measured glucose level may be a glucose level measured manually by the subject or an authorized user (e.g., a guardian or parent of the subject), for example, using a glucose monitor and glucose test strips.
  • the controller 4102 may delay, expedite medicament delivery, reduce or increase a medicament dose, or modify the corresponding glucose levels and generate a dose control signal based on the modified glucose levels.
  • the GLCS 4100 may use an artifact management algorithm to analyze one or more sensor signals received from one or more sensors (e.g., heart rate sensors, pressure sensors, motion sensors, temperature sensors and the like) and delay/expedite the delivery of medicament or increase/reduce the medicament dose based on the artifact and the one or more sensor signals.
  • sensors e.g., heart rate sensors, pressure sensors, motion sensors, temperature sensors and the like
  • the controller 4102 may suspend the delivery of medicament for a suspension period.
  • the suspension period may be determined based at least in part on the identified artifact, sensor signals received from one or more sensors (e.g., heart rate sensors, pressure sensors, motion sensors, temperature sensors and the like), diurnal period during which the artifact is identified, the glucose levels decoded from one or more glucose level signals, or the last medicament dose and/or medicament type delivered to the subject.
  • sensors e.g., heart rate sensors, pressure sensors, motion sensors, temperature sensors and the like
  • the GLCS 4100 may determine a diurnal period during which the corresponding glucose level signals were received and delay delivery of medicament based at least in part on the determined diurnal period.
  • the GLCS 4100 may temporarily delay the delivery of a dose of medicament in response to glucose level excursions associated with the glucose level data.
  • the controller 4102 may determine a level of movement and/or activity of the subject 4118.
  • the controller 4102 may determine the level of movement and/or activity of the subject 4118, based at least in part on one or more motion signals received from one or more motion sensors connected to the subject 4118, indicative of level of movement of a subject 4118.
  • the controller 4102 may determine the level of movement and/or activity of the subject 4118, based at least in part on one or more sensor signals received from a heart rate sensor or a temperature sensor operatively connected to the subject 4118.
  • the controller 4102 may determine that the subject 4118 has been inactive (e.g., has not moved) during a time period larger than a threshold time period indicating that an artificially low glucose level associated with an artifact identified during the corresponding time period, may be associated with pressure applied on the glucose sensor due to subject’s body position. In such examples, the controller 4102 may delay the delivery of the medicament until a motion signal received from the motion sensor indicates that subject has moved. Once the controller 4102 determines that the subject has moved, it may analyze glucose level data associated with a first glucose level signal, or first few glucose level signals received after detecting the subject’s motion, and if no artifact is identified, generate a dose control signal based on the glucose level data.
  • the controller 4102 may delay the delivery of insulin to the subject 4118 by at least 2 hours, 4 hours, or 5 hours compared to an initial insulin delivery time associated with the glucose level data. Alternatively, or in addition, the controller 4102 may determine whether a time of the day during which the one or more artifacts are identified overlaps with a time period during which a physical activity (e.g., exercise, hiking, and the like) is scheduled and delay the delivery of insulin to the subject 4118 compared to an initial insulin delivery time associated with the glucose level data.
  • a physical activity e.g., exercise, hiking, and the like
  • the controller 4102 may use a sensor signal received from a pressure sensor connected to the subject to determine whether pressure is applied on or near the glucose sensor 4116 and delay the delivery of medicament until receiving the a sensor signal that indicates the pressure is removed from the glucose sensor and/or the an area near the glucose sensor.
  • the GLCS 4100 may deliver restricted glucose therapy to the subject.
  • the restricted glucose therapy may be a capped therapy.
  • the controller 4102 may impose a maximum limit on a dose of medicament (e.g., insulin or glucagon) delivered based on the glucose level data that contains the artifact.
  • a restricted therapy may be a scaled therapy.
  • the controller 4102 may scale up or scale down the dose of medicament (e.g., insulin or glucagon) compared to a calculated dose of medicament associated with the glucose level data that contains the artifact.
  • the controller 4102 may determine a scaling factor by which the dose of medicament is changed compared a dose of medicament associated with the glucose level data that contains the artifact.
  • the controller 4102 may determine the scaling factor based at least in part on the characteristics of the identified artifact or a history of the glycemic control of the subject (e.g., associated with preceding medicament doses delivered).
  • the characteristics of the identified artifact may include, for example: values of glucose level, glucose level velocities, or glucose level accelerations associated with the artifact.
  • the GLCS 4100 may generate a substitute dose control signal based at least in part on the one the one or more artifacts or portion of the glucose level data that includes the artifacts.
  • generating a substitute dose control signal may comprise generating a dose control signal based on a glucose level signal received after receiving the one or more glucose level signals associated with the artifacts or after a measurement period during which the glucose level data that contains one or more artifacts is received.
  • the substitute dose control signal may be delivered to the medicament delivery system 4112 and result in delivery of substitute glucose control therapy.
  • the substitute glucose control therapy may be associated with an artifact compensation process used by a control algorithm executed by the controller 4102 in an artifact compensation mode.
  • the substitute glucose control therapy may be a restricted therapy, or delayed therapy or an offline therapy.
  • the substitute dose control signal may be determined based at least in part on whether the corresponding artifact is an artificially low or an artificially high glucose level. For example, if the artifact is an artificially low glucose level, substitute dose control signal may be a dose control signal that results in restricted delivery of insulin to the subject.
  • a restricted delivery of insulin can be delivery of a dose of insulin later than a delivery time associated with a dose control signal that could be generated based on the artifact. In some examples, a restricted delivery of insulin can be delivery of a dose of insulin smaller than dose associated with a dose control signal that could be generated based on the artifact.
  • the controller 4102 may generate a substitute dose control signal based at least in part on a history of glycemic control of the subject.
  • the substitute dose may be generated based at least in part on one or more glucose level signals received or dose control signals generated during a time period before a time period during which one or more artifacts or the portion of the glucose level data that contains an artifact, are received or measured.
  • the controller 4102 may generate the substitute dose control signal based at least in part on the time of the day at which the glucose level signals associated the one or more artifacts are received. In some embodiments, the controller 4102 may generate the substitute dose control signal based at least in part on the one or more dose control signals generated during a time period before the time period during which the one or more artifacts are identified.
  • the controller 4102 may generate the substitute dose control signal based at least in part on one or more sensor signals received from one or more sensors (e.g., motion sensor, blood pressure sensor, heart rate sensor and the like). [0677] In some implementations, the controller 4102 may generate the substitute dose control signal based at least in part on one or more modified glucose levels. In some such implementations, the controller 4102 may use an artifact modification algorithm to generate the one or more modified glucose levels to replace the artifacts or all the glucose level signals (including artifacts) included in glucose level data that includes one or more artifacts. In some cases, controller 4102 may generate substitute dose control signals only for glucose level signals received during the artifact time window determined by the controller 4102.
  • the controller 4102 may generate the modified glucose levels by generating averaged glucose level data, smoothed glucose level data or filtered glucose level data using the entire or a portion of the glucose level data.
  • the filtered glucose level data may be generated by calculating a Fourier transform of the entire or a portion of the glucose level data and discarding glucose levels associated with frequency components larger than a threshold frequency.
  • the controller 4102 may use the artifact modification algorithm to generate the one or more modified glucose level signals (or modified glucose level signals) based at least in part on: one or more glucose therapies delivered to the subject 4118 before receiving the glucose level data that includes the identified artifacts, one or more glucose level signals received before receiving glucose level signals associated with the artifacts, a history of the glycemic control of the subject 4118 stored in a memory of the GLCS 4100, one or more sensor signals received from one or more sensors, and/or a diurnal period and a day during which the receiving glucose level signals associated with the artifacts are received.
  • FIG. 34 shows an example of glucose level data 4300 that includes several glucose levels that may be identified as artifacts.
  • the glucose level 4304a may be identified as an artifact because it is larger than a maximum glucose level (e.g., the maximum glucose level 4210) and indicates a velocity larger than a jump threshold velocity.
  • the glucose level 4308a may be identified as an artifact because it is smaller than a minimum glucose level (e.g., the minimum glucose level 4206) and indicates a velocity larger than a drop threshold velocity.
  • glucose level 4306a may be identified as artifact because it represents a velocity larger than a jump threshold velocity.
  • the controller 4102 may identify an artifact time window 4302 and use the artifact modification algorithm to generate one or more modified glucose levels to replace the originally received glucose level signals. For example, the controller 4102 may replace glucose level glucose levels 4304a, 4306a and 4308a with modified glucose levels 4304b, 4306b and 4308b. Alternatively, using the artifact modification algorithm, the controller 4102 may calculate a modified glucose level variation curve 4310 based at least in part on normal glucose level signals included in the artifact time window 4302, glucose level signals received before the artifact time window 4302, and dose control signals generated before the artifact time window 4302.
  • the controller 4102 may use the modified glucose level variation curve 4310 to calculate the substitute or modified glucose level glucose levels 4304b, 4306b and 4308b.
  • the controller 4102 may use the glucose level variation curve 4310, and/or the modified glucose levels 4304b, 4306b and 4308b to generate the substitute dose control signal.
  • FIG. 35 is a flow diagram showing an example of a computer-implemented method or process 4400 that may be used by GLCS 4100 to manage glucose control therapy delivered to a subject in the presence and absence of an artifact in the received glucose level data.
  • the process 4400 begins at block 4402 where the GLCS 4100 receives one or more glucose level signals from the glucose sensor 4116 (e.g., a CGM). In some cases, the glucose sensor 4116 may transmit the glucose level signals to the glucose sensor interface 4122 of the GLCS 4100 via a wired or a wireless link. Subsequently the controller 4102 may receive the glucose level signals from the glucose sensor interface 4122.
  • the glucose sensor 4116 e.g., a CGM
  • the glucose sensor 4116 may transmit the glucose level signals to the glucose sensor interface 4122 of the GLCS 4100 via a wired or a wireless link.
  • the controller 4102 may receive the glucose level signals from the glucose sensor interface 4122.
  • the glucose level signals may be proportional to glucose levels of the subject 4118.
  • the glucose level signals may comprise encoded glucose levels (e.g., the measured glucose levels) and the GLCS 4100 may decode the glucose levels from the glucose level signals.
  • the controller of 4102 generates an initial dose control signal based at least in part on the glucose levels decoded from the glucose level signals received at block 4402.
  • the initial dose control signal may indicate a medicament type, an initial medicament dose and an initial medicament delivery time.
  • the dose control signal may comprise the medicament type, the initial medicament dose, and the initial medicament delivery time.
  • the controller 4102 may generate the initial dose control signal using a control algorithm and the values of one or more control parameters.
  • the control algorithm may be implemented via execution of machine-readable instructions stored in memory 4110 of the controller 4102.
  • the controller 4102 may decode glucose levels of the subject from the received glucose level signal and use the control algorithm to determine the medicament type, the medicament delivery time and the medicament dose based at least in part on the measured values of the glucose level.
  • the GLCS 4100 may analyze the one or more glucose level signals to determine to identify artifacts.
  • the GLCS 4100 may identify an artifact based on the last glucose level signal received.
  • the GLCS 4100 may identify an artifact based on the last glucose level signal received and one or more glucose level signals received before the last glucose level signal.
  • the controller 4102 of the GLCS 4100 may analyze the glucose levels associated with the received glucose level signals using one of the artifact detection methods described herein, for example methods described with respect to FIG. 33 A-7C.
  • the controller 4102 may implement an artifact detection process using one or more artifact detection algorithms.
  • the artifact detection algorithm may be stored as machine readable instructions in the memory 4110 and executed by the processor 4104 of the controller 4102.
  • the artifact detection process may include a comparison between the time of day during which the first glucose level signal is received, and one more reference times of the day stored in a memory of the ambulatory medicament pump.
  • the reference times of the day may correspond to times or periods associated with activities that may affect the glucose level in a subject.
  • the artifact detection algorithm may identify the artifact based at least in part on one or more medicament therapies delivered to the subject before receiving the glucose level signal at block 4402.
  • the GLCS 4100 if no artifact is identified based on the analysis performed at block 4406, the process proceeds to block 4410 where the controller 4102 transmits the initial dose control signal, generated at block 4404, to the medicament delivery system 4112.
  • the controller 4102 may transmit the dose control signal to a pump controller in the medicament delivery system.
  • the pump controller Upon receiving the initial dose control signal, the pump controller causes a medicament pump to infuse the initial medicament dose to the subject 4118 at the initial medicament delivery time.
  • the process proceeds to block 4412, where the controller 4102 modifies the initial dose control signal, generated at block 4404, based at least in part on the identified artifact.
  • the resulting modified dose control signal may correspond to a reduced medicament dose and/or a delayed medicament delivery time with respect to the initial medicament dose and the initial medicament delivery time.
  • the resulting modified dose control signal may correspond to an increased medicament dose and/or an early delivery of a medicament with respect to the initial medicament dose and the initial medicament delivery time.
  • the controller 4102 may modify the signal based at least in part on a diurnal period during which the one or more glucose level signals have been received.
  • the controller 4102 may modify the glucose level signal based at least in part on one or more dose control signals generated before receiving the glucose level signal at block 4402.
  • the modified dose control signal may be transmitted to the medicament delivery system 4112.
  • the modified dose control signal may cause the delivery system 4112 to deliver, at the initial delivery time, a reduced dose of medicament compared to the initial medicament dose corresponding to the initial dose control signal, to the subject 4118.
  • the modified dose control signal may delay the delivery of the initial medicament dose to the subject 4118, by the delivery system 4112, compared to the initial medicament delivery time associated with the initial dose control signal.
  • the modified dose control signal may cause the delivery system 4112 to deliver a reduced dose of medicament to the subject 4118, compared to the initial medicament dose, at a delayed delivery time compared to the initial medicament delivery time.
  • the modified dose control signal may cause the delivery system 4112 to deliver, at the initial delivery time, an increased dose of medicament compared to the initial medicament dose corresponding to the initial dose control signal, to the subject 4118.
  • the modified dose control signal may result in early delivery of the initial medicament dose to the subject 4118, by the delivery system 4112, compared to the initial medicament delivery time associated with the initial dose control signal.
  • the modified dose control signal may cause early delivery of an increased dose of medicament to the subject 4118, compared to the initial delivery time and initial medicament dose.
  • FIG. 36 is a flow diagram showing another example of a computer-implemented method or process 4400 that may be used by an GLCS to manage glucose control therapy delivered to a subject in the presence and absence of an artifact in the received glucose level signal.
  • the process 4500 may include one or more features described with respect to the process 4400.
  • the process 4500 begins at block 4502 where the GLCS 4100 receives a first group of glucose level signals from the glucose sensor 4116 (e.g., a CGM sensor).
  • the glucose sensor 4116 may transmit the glucose level signals to the glucose sensor interface 4122 of the GLCS 4100 via a wired or a wireless link.
  • the controller 4102 may receive the glucose level signals from the glucose sensor interface 4122.
  • the glucose level signals may be stored in a memory of the GLCS 4100.
  • the first group of glucose level signals may comprise a first glucose level signal.
  • the first group of glucose level signals may include two or more glucose level signals.
  • the controller 4102 may decode a first group of glucose levels from the first group of glucose level signals and generate an initial dose control signal based at least in part on the first group of glucose levels.
  • the GLCS 4100 may analyze the first group of glucose levels to identify artifacts using one or more artifact identification methods and one or more artifact detection algorithms.
  • the process proceeds to block 4512 where the controller 4102 delays the delivery of medicament.
  • the controller 4102 may send an electronic request to the glucose sensor 4116 to cause generation of the one or more additional glucose level signals.
  • the controller may delay the delivery of the medicament until a set number of additional glucose level signals are received.
  • the controller 4102 may receive a second group of glucose level signals from the glucose sensor 4116.
  • the second group of glucose level signals may comprise a second glucose level signal.
  • the second group of glucose level signals may include two or more glucose level signals.
  • a number of glucose levels in the second group of glucose level signals may be larger than a number of glucose level signals in the first group of glucose level signals.
  • the second group of glucose level signals may be received from a second glucose sensor connected to the subject.
  • the controller 4102 may decode a second group of glucose levels from the second group of glucose level signals and generate a second dose control signal based at least in part on the second group of glucose levels.
  • controller 4102 may analyze the second group of glucose levels to identify one or more artifacts.
  • the modified dose control signal may be transmitted to the medicament delivery system 4112 and cause the delivery of medicament to the subject based on the modified dose control signal.
  • FIG. 37 is a flow diagram showing another example of a computer-implemented method or process 4600 that may be used by an GLCS 4100 to manage glucose control therapy delivered to a subject in the presence and absence of an artifact in the received glucose level signal.
  • the process 4600 may include one or more features described with respect to the process 4400 and/or the process 4500.
  • the process 4600 begins at block 4602 where the controller 4102 of the GLCS 4100 analyzes the glucose level data received from the glucose sensor 4116 to identify one or more artifacts.
  • the glucose level data may include one or more glucose levels decoded from one or more glucose level signals received from the glucose sensor 4116.
  • the process may proceed to block 4606 where the controller 4102 generates a dose control signal based at least in part on the glucose level data received at block 4602 and transmits the dose control signal to the medicament deliver system 4112.
  • a substitute dose control signal may be generated based on a portion of the glucose level data (e.g., a portion received during an artifact time window).
  • the controller 4102 may generate the substitute dose control signal based at least in part, on: a diurnal period during which the glucose level data is received, one or more sensor signals received from one or more sensors, one or more dose control signals generated before receiving the glucose level data that contains the identified artifacts, a glycemic history of the subject 4118, glucose level data received before receiving the glucose level data that contains the identified artifacts.
  • the controller 4102 may deliver substitute glucose control therapy to the subject 4118, based on the substitute dose control signals generated at block 4608.
  • the substitute glucose control therapy may be delivery of a reduced or an increased dose of a medicament (e.g., insulin or glucagon) compared to a dose determined based on the glucose level data analyzed at block 4602.
  • substitute glucose control therapy may be an early or delayed delivery of a medicament to the subject 4118 compared to a delivery time determined based on the glucose level data received at block 4602.
  • substitute glucose control therapy may be an offline deliver of medicament, for example, based on one or more isolated glucose measurement (e.g., glucose levels measured by a user or the subject and provided to the GLCS 4100 via a user interface).
  • FIG. 38 is a flow diagram showing another example of a computer-implemented method or process 4700 that may be used by an GLCS 4100 (e.g., the controller 4102 of the GLCS 4100) to manage glucose control therapy delivered to a subject in the presence and absence of an artifact in the received glucose level signal.
  • the process 4700 may include one or more features described with respect to the process 4400, and/or process 4500 and/or the process 4600.
  • the process 4700 begins at block 4702 where the controller 4102 of the GLCS 4100 analyzes the glucose level data decoded from the glucose level signals received from the glucose sensor 4116 to identify one or more artifacts.
  • the decision to block 4704 may use the outcome of the analysis performed at block 4702 to determine whether the glucose level data includes an artifact. If at decision block 4704, the controller of 4102 does not identify an artifact in the glucose level data, the process may proceed to block 4706, the controller 4102 may generate a dose control signal based at least in part on the glucose level data received at block 4602 and transmit the dose control signal to the medicament deliver system 4112.
  • the process may proceed to decision block 4708 where the controller 4102 determines whether the artifact is an artificially low artifact. If at decision block 4708 the controller determines that the artifact is not an artificially low glucose level, the process may proceed to block 4710 where the controller generates a substitute dose control signal and transmits the dose control signal to the medicament delivery system 4112.
  • the process may proceed to decision block 4712 where the controller 4102 determines a level of motion or activity of the subject 4118.
  • the controller 4102 may determine the level of motion or an activity of the subject 4118 based on a diurnal period and the day during which the glucose level data that includes the identified artifact is received.
  • the controller 4102 may determine whether the glucose level data (that includes the identified artifact) has been received during a time period that overlaps with a sleeping or an exercise time period during which the subject may be sleeping or moving.
  • one or more sleeping or exercise time periods may have been provided by a user of the GLCS 4100 or the subject receiving therapy from the GLCS 4100 and stored in a memory of the GLCS 4100.
  • the controller 4102 may determine the one or more sleeping or exercise time periods by analyzing a sensor signals received from one or more sensors during an extended time period before the time period during which the glucose level data is received.
  • the controller 4102 may analyze one or more sensor signals (e.g., motion signals, or heart rate signals) received from one or more sensors (e.g., a motions sensor, or a heart rate sensor) to determine an activity of level of motion of the subject.
  • the sensor signals may be continuously or periodically transmitted to the controller 4102.
  • the sensor signals may be stored in a memory (e.g., memory 4110 of the controller 4102).
  • the controller 4102 may analyze one or more sensor signals received before receiving the glucose level data that includes the identified artifacts.
  • the controller 4102 may analyze one or more sensor signals received during a time period when the glucose level data that includes the identified artifacts, is received.
  • the process may proceed to block 4710 where the controller generates a substitute dose control signal and transmits the dose control signal to the medicament delivery system 4112.
  • the process may proceed to block 4714 where the controller 4102 delays the delivery of medicament until the subject moves or becomes active.
  • the controller 4102 may determine whether the subject has moved or became active. Upon determining whether the subject has moved or became active, the control may use the first glucose level signal received after determining the subject has moved or became active, to generate a dose control signal.
  • FIG. 39 is a flow diagram showing an example of a computer-implemented method or process 4800 that may be used by GLCS 4100 (e.g., the controller 4102 of the GLCS 4100) to adjust the glucose control therapy delivered to a subject by an ambulatory medicament pump in response to identifying a glucose level artifact in glucose level data.
  • the process 4800 may include one or more features described with respect to the process 4400, and/or process 4500 and/or process 4600 and/or the process 4700.
  • the GLCS 4100 receives one or more glucose level signals from the glucose sensor 4116 via the glucose sensor interface 4122.
  • the GLCS 4100 decodes glucose level data from the glucose level signal. [0717] At decision block 4806 the GLCS 4100 determines whether the glucose level data has a glucose level artifact.
  • the process proceeds to block 4808 where the GLCS 4100 generates a dose control signal based at least in part on the glucose level data.
  • the process proceeds to block 4810 where the GLCS 4100 operates a control algorithm in an artifact compensation mode to generate a dose control signal.
  • the GLCS 4100 may select the artifact compensation mode based at least in part on the detected artifact.
  • the artifact compensation mode can implement one or more artifact compensation processes, which can include delaying doses of medicament in response to glucose level excursions, reducing doses of medicament in response to glucose level excursions, expediting doses of medicament in response to glucose level excursions, increasing doses of medicament in response to glucose level excursions, generating the dose control signal using an offline mode of operation, or a combination of processes.
  • delaying, reducing, or increasing doses of medicament comprises temporarily delaying, reducing, or increasing doses of medicament.
  • compensation processes may restrict therapy delivery by capping or scaling the associated doses of medicament.
  • the controller 4102 may impose a limit (e.g., a maximum limit) on a dose of medicament (e.g., insulin or glucagon) that may be delivered based on the glucose level data that contains the artifact.
  • a limit e.g., a maximum limit
  • the controller 4102 may scale up or scale down the dose of medicament (e.g., insulin or glucagon) compared to a dose medicament associated with the glucose level data that contains the artifact.
  • the controller 4102 may determine a scaling factor by which the dose of medicament is changed compared a dose of medicament associated with the glucose level data that contains the artifact.
  • the controller 4102 may determine the scaling factor based at least in part on the characteristics of the identified artifact or a history of the glycemic control of the subject (e.g., associated with preceding medicament doses delivered).
  • the characteristics of the identified artifact may include, for example: values of glucose level, glucose level velocities or glucose level accelerations associated with the artifact.
  • an artifact compensation process may operate the control algorithm in an offline mode where the control algorithm generates the dose control signal when the glucose level data associated with the glucose level signal without using the glucose level data.
  • the controller 4102 may send a user notification to a user interface (e.g., a user interface of the GLCS 4100) requesting a measured glucose level value to be provided via the user interface.
  • a user interface e.g., a user interface of the GLCS 4100
  • the GLCS 4100 may display a message on a touchscreen display indicating that an artifact has been detected and that, to proceed with the glucose level therapy, a measured glucose level should be provided via the touchscreen display or via another glucose level entry interface.
  • a measured glucose level may be a glucose level measured by another glucose sensor (e.g., a test strip-based sensor or another CGM) that is not in communication with the GLCS 4100.
  • a measured glucose level may be a glucose level measured manually by the subject or an authorized user (e.g., a guardian or parent of the subject), for example, using a glucose monitor and glucose test strips.
  • an artifact compensation process may include generate a modified glucose level and generate the dose control signal using the modified glucose level.
  • the modified glucose level may be different from glucose levels decoded from the glucose level data.
  • the GLCS 4100 may notify the subject of the glucose level artifact by generating a user notification.
  • the notification may be a text message or a visual indicator displayed on a display (e.g., a touchscreen display) of the GLCS 4100.
  • the notification may be displayed on a lock screen of the GLCS 4100.
  • FIG. 40 illustrates a block diagram showing an example glucose level control system 4900 that includes an artifact detection system 4902 and a dose control generation system 4906 with artifact mode .
  • the artifact detection system 4902 may analyze the glucose level data decoded from glucose level signals received from a glucose sensor to identify an artifact.
  • the artifact detection system 4902 may use one or more artifact detection algorithms 4904 stored in a memory of the glucose level control system 4900, to identify the artifact.
  • the artifact detection system 4902 may identify the artifact in the glucose data using one or more of the example methods described in the section titled Identifying an artifact in glucose level data or using another method. Subsequently the artifact detection system 4902 may generate and send artifact data 4905 to the dose control generation system 4906. In some cases, the artifact data 4905 may include a type of artifact identified (e.g., an artificially low glucose level, an artificially high glucose levels, an artifact associated with a velocity of glucose level, an artifact associated with an acceleration of the glucose level, and the like).
  • a type of artifact identified e.g., an artificially low glucose level, an artificially high glucose levels, an artifact associated with a velocity of glucose level, an artifact associated with an acceleration of the glucose level, and the like.
  • the artifact data 4905 may include data usable to quantify the artifact, and to select an artifact compensation process that may be used to generate a dose control signal in response to the detection of the artifact. In some cases, such dose control signal may reduce the risk of hyperglycemia or hypoglycemia in the subject.
  • the artifact data 4905 may include an amount of by which an acceleration, a residual value, or a velocity of a glucose level associated with the artifact exceeds a threshold value (e.g., threshold acceleration, drop threshold velocity, jump threshold velocity, and the like).
  • the artifact data 4905 may also include data received from a sensor (e.g., heart rate sensor, motion sensors, and pressure sensor)
  • the dose control generation system 4906 may select the artifact compensation process and operate the control algorithm of the control algorithms 4920 stored in a memory of the glucose level control system 4900 in the corresponding artifact compensation mode.
  • the control algorithms 4920 may include control algorithms for generating correction doses 4922 (e.g., a model predictive control algorithm), generating meal doses 4924, or generating basal doses 4926.
  • the dose control generation system 4906 may select the artifact compensation process based at least in part on the artifact data 4905.
  • Artifact compensation processes may include: delaying doses of medicament 4908, reducing doses of medicament 4910, expediting doses of medicament 4912, increasing doses of medicament 4914, operating the control algorithm in an offline mode 4916, or generating the dose control signal using a modified glucose level 4918.
  • the dose control generation system 4906 may operate a control algorithm in the artifact compensation mode associated with the selected artifact compensation process to generate a dose control signal 404 and send the dose control signal to the medicament delivery system 4112.
  • the hesitancy may be for any number of subjective or objective reasons.
  • the hesitancy may relate to the subjects’ confidence in their ability to best manage their disease based on their experience or general distrust in giving up control.
  • the hesitancy may relate to bad experiences with older diabetes management systems.
  • even subjects that are confident in the ability of the glucose level control systems to maintain their disease may at times desire manual control or the ability to manually modify recommendations or control or of the glucose level control systems.
  • a subject who is anticipating unusual activity for the subject e.g., increase or decrease in exercise, unusual meal selections, etc.
  • Embodiments of the glucose level control system 510 can generate or calculate an insulin dose or insulin dose rate using one or more control algorithms described in the patents and publications incorporated by reference above. Further, the glucose level control system 510 can output an indication of the calculated insulin dose on a user interface that permits a user or subject to manually modify the calculated insulin dose.
  • permitting a user to manually modify the calculated insulin dose enables the user to assert control over maintenance of a subject’s diabetes while at least partially maintaining closed loop and/or automatic maintenance of the subject’s diabetes.
  • the glucose level control system 510 may continue to receive one or more glucose level readings from a glucose sensor 516. Using the glucose level readings, the glucose level control system 510 may automatically adjust subsequent calculated insulin doses and/or cease using the manually modified insulin doses upon detection of a trigger, such as a risk of adverse health consequences.
  • FIG. 41 illustrates a flowchart of an example process 5000 directed to manual modification of an autonomously generated medicament dose in accordance with certain embodiments.
  • the process 5000 can be implemented by any system that can operate using a control algorithm used by an ambulatory medical device to automatically determine a medicament dose and administer the medicament to a subject and enable a user to manually adjust the automatically determined medicament dose.
  • the process 5000 in whole or in part, can be implemented by, for example, an ambulatory medical device 100, a glucose level control system 200, a glucose level control system 510, a controller 202, a controller 518, a processor 530, a glucagon controller 622, a basal controller 624, a corrective insulin controller 626 (e.g., a model predictive controller), a priming insulin controller 628 (e.g., a meal controller), a glucose sensor 516, or a glucose sensor interface that interfaces with the glucose sensor 516, among others.
  • a corrective insulin controller 626 e.g., a model predictive controller
  • a priming insulin controller 628 e.g., a meal controller
  • glucose sensor 516 e.g., a meal controller
  • any number of systems, in whole or in part, can implement the process 5000 to simplify discussion, the process 5000 will be described with respect to particular systems.
  • the process may begin at block 5002 where, for example, the glucose level control system 510 automatically provides therapy to a subject over a first time period.
  • Providing therapy to the subject may include using a control algorithm that is configured to generate dose control signals to administer insulin doses to the subject.
  • the control algorithm may include any of the control algorithms described in the patents and publications previously incorporated by reference herein.
  • the control algorithm may be an adaptive closed-loop algorithm that adjusts insulin dosing based at least in part on glucose signals received from a glucose sensor coupled to the subject.
  • the block 5002 may be optional or omitted.
  • features of the process 5000 may be applicable to first-time users and/or during an initial administration of therapy.
  • the first time period may be a set period of time.
  • the first time period may be a training period or some other period of time specified by a user or the glucose level control system 510.
  • the first time period may be an indefinite period of time.
  • the first time period may be from the start of operation of the glucose level control system 510, or some other designated start time, until a modification of an insulin dose value is received at the block 5008 as described further herein.
  • the first time period may be defined by a user after occurrence of the first time period. For example, a user may specify a historical or past period of time as the first time period.
  • the glucose level control system 510 generates a calculated insulin dose based at least in part on the therapy provided to the subject over the first time period.
  • the calculated insulin dose may be further based at least in part on one or more glucose level signals received from one or more glucose sensors 516.
  • some features of the process 5000 may be applicable during an initial administration of therapy.
  • the calculated insulin dose at the block 5004 may not be based on prior therapy or therapy over the first time period, but may instead be based on the one or more glucose level signals received from the one or more glucose sensors 516 and/or based on clinical data provided to the glucose level control system 510.
  • the calculated insulin dose may include a plurality of insulin doses. Further, the calculated insulin dose may be a dose rate rather than a single dose.
  • the calculated insulin dose may include a basal rate.
  • the basal rate may be for a particular time period or segment of a day.
  • the calculated basal rate may be for a six hour period, an eight hour period, a 12 hour period, associated with daytime, associated with nighttime, or any other division of a day or time period.
  • the calculated insulin dose may include a plurality of calculated insulin dose rates. Further, at least some of the plurality of calculated insulin dose rates may be associated with different segments of the day in at least some other of the calculated insulin dose rates. For example, at least one of the calculated insulin dose rates may be a basal rate associated with one portion of the day and at least one other of the plurality of calculated insulin dose rates may be a basal rate associated with another portion of the day.
  • the calculated insulin dose may be an initial basal rate calculated based on physiological data associated with the subject.
  • Physiological data may include any physiological characteristics that can affect the maintenance of the subject’s diabetes.
  • the physiological data may include age, weight, sex or gender, length of time since the subject became diabetic, severity of the subject’s diabetes, etc.
  • the calculated insulin dose may be a dose rate, such as a basal rate. Further, the calculated insulin dose may be a meal dose. The meal dose may be associated with a particular meal, meal time, meal size, or meal type. Alternatively, the calculated insulin dose may be a correction dose.
  • the glucose level control system 510 may determine a correction dose using a model predictive controller configured to execute a control algorithm. The control algorithm may determine a correction dose to adjust a subject’s glucose level to bring it within a glucose setpoint range or to bring it closer to a center or other point within a glucose setpoint range. In some cases, the calculated insulin dose may vary based on the medicament that the glucose level control system 510 has access. For example, the glucose level control system 510 may determine a particular insulin dose when a particular type of insulin is available, when only insulin is available, or when both insulin and a counter regulatory agent (e.g., Glucagon) is available.
  • a counter regulatory agent e.g., Glucagon
  • the glucose level control system 510 outputs an indication of the calculated insulin dose on a display.
  • the display may be part of the glucose level control system 510.
  • outputting the indication of the calculated insulin dose may include causing the indication of the calculated insulin dose to be output on another device, such as an electronic device in wired or wireless communication with the glucose level control system 510.
  • the block 5006 may include causing the indication of the calculated insulin dose to be displayed on a control device, a smart phone, a smartwatch, a tablet, or any other electronic device that may communicate with the glucose level control system 510.
  • the block 5006 is optional or omitted.
  • a user may manually modify a calculated insulin dose without accessing the specific calculated insulin dose value.
  • a user may adjust or scale (e.g., increase or decrease by 5%, 10%, 12%, etc.) calculated insulin doses without being aware of the specific insulin dose values.
  • the glucose level control system 510 receives an indication of a modification to the calculated insulin dose to obtain a modified insulin dose.
  • the indication of the modification to the calculated insulin dose may be received in response to and/or based on user input.
  • This user input may be received in response to interaction with a user interface by a user.
  • the user may be the subject receiving therapy and/or another user, such as a parent, guardian, healthcare provider, or other user that may be permitted to provide commands or otherwise interact with the glucose level control system 510.
  • a parent, guardian, healthcare provider or other user that may be permitted to provide commands or otherwise interact with the glucose level control system 510.
  • the modification to the calculated insulin dose may include a modification to a single insulin dose or a modification to a plurality of calculated insulin doses.
  • modification to the calculated insulin dose may include a modification to an insulin dose rate.
  • the calculated insulin dose may be a basal rate.
  • the modification to the calculated insulin dose may be a modification to the basal rate.
  • the modification to the basal rate may be a modification to each calculated basal rate of a plurality of calculated basal rates or may be modification to a particular basal rate of the plurality of calculated basal rates.
  • a modification to a calculated insulin dose may include a modification to some calculated basal rates, but not other calculated basal rates of the plurality of calculated basal rates.
  • at least one of the calculated basal rates may be omitted from the modification of the calculated basal rates and may remain unmodified.
  • a basal rate associated with the daytime may be modified while a basal rate associated with nighttime may remain unmodified.
  • the calculated insulin dose may include a calculated basal rate.
  • This calculated basal rate may include a nominal basal rate and/or an instantaneous basal rate.
  • the nominal basal rate is adapted more slowly over time than the instantaneous basal rate.
  • the indication of the modification to the calculated insulin dose may be an indication of a basal rate or associated with a basal rate.
  • the indication of the modification to the calculated insulin dose may be a new nominal basal rate or a change to the nominal basal rate.
  • indication of the modified basal rate may be associated with an event or a particular time period.
  • modified basal rate may be associated with a particular time of day.
  • the modified basal rate may be associated with an exercise event or a sickness event, such as an indication the subject has the flu.
  • the glucose level control system 510 may switch the calculated basal rate for a modified basal rate based at least in part on the indication of the modification to the basal rate. In some cases, switching the calculated basal rate to the modified basal rate may modify a basal rate around which the instantaneous basal rate varies. This basal rate around which the instantaneous basal rate varies may be a nominal basal rate. Further, the calculated insulin dose may be an adapted basal rate that is adapted over time based at least in part on one or more glucose level signals received from a glucose sensor operative to determine a glucose level of the subject.
  • the indication of the modification to the calculated insulin dose may include an indication of a change in a percentage of the total daily dose of insulin for the subject to apply as basal insulin for the subject.
  • the user may specify that the basal rate should be modified to cover a different percentage or a particular percentage of the total daily dose (TDD) of insulin.
  • TDD total daily dose
  • the indication of the modification to the calculated insulin dose may specify that the basal rate provide 35% or 40% of the subjects TDD of insulin.
  • the indication of the modification to the calculated insulin dose may include a specific value for the insulin dose.
  • the modification of the calculated insulin dose may identify a specific number of units of insulin to administer to the user or a specific rate of insulin to supply to the user.
  • the specific rate of insulin may include a time period for which the specific rate should be supplied to the user.

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Abstract

Un système de régulation du glucose peut être conçu pour calculer, mettre en œuvre, afficher ou modifier un traitement de régulation du glucose chez un sujet. Le système de régulation du glucose peut mettre en œuvre de telles actions par l'intermédiaire d'une pompe à médicament, par l'intermédiaire d'une indication d'utilisateur, l'utilisateur mettant en œuvre manuellement le traitement, par l'intermédiaire de la sélection d'un mode de fonctionnement ou toute combinaison de ces éléments. Le système peut déterminer l'administration d'un traitement de régulation du glucose en raison d'une condition détectée, d'une interaction détectée, d'un événement hypoglycémique déterminé, d'une interaction d'utilisateur déterminée ou d'un artefact déterminé. Le système de régulation du glucose peut reposer sur certaines valeurs de seuil ou sur des critères qui peuvent être dynamiques ou fixes dans la détermination d'un traitement.
PCT/US2022/027531 2021-05-04 2022-05-03 Systèmes et procédés de régulation du taux de glucose WO2022235714A1 (fr)

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WO2024197057A1 (fr) * 2023-03-22 2024-09-26 Know Labs, Inc. Système et procédé d'activation de logiciel et de matériel sur la base de paramètres de santé en temps réel

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