RU2778069C2 - Accounting for residual amount of active insulin in artificial pancreas system - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to the field of systems for control of a blood glucose level, more specifically, to a system for control of a blood glucose level with feedback, such as an artificial pancreas system, which uses a controller using more than one model for accounting for the residual amount of active insulin. A method for accounting for the residual amount of active insulin in a system for measuring a glucose level is described, wherein the system includes a controller. The method contains following stages, which provide for: calculation of the amount of bolus calculated by the system; after calculation of the amount of bolus calculated by the system, administration to a user of the amount of insulin bolus initiated by the user; after administration of the amount of bolus initiated by the user, determination of whether the user has entered a value of blood glucose (hereinafter – BG) concentration into the controller; after determination of whether the user has entered the BG concentration value into the controller, determination of whether the user has entered a value of carbohydrates (hereinafter – CHO) into the controller; if it is determined by the controller that the user entered the BG concentration value into the controller, but did not enter the CHO value, then, the calculation of a component of blood glucose correction for the amount of insulin bolus initiated by the user is carried out based on the BG concentration value, by means of the controller, as follows:

,

where the total amount is the total amount of the amount of insulin bolus initiated by the user, the target value is the target value of the blood glucose level, ISF is a given insulin sensitivity factor, and PFIOB is a value of the patient-oriented residual amount of active insulin; if it is determined that the user did not enter the BG concentration value into the controller, but entered the CHO value, then the calculation, using the controller, of a food component for the amount of insulin bolus initiated by the user is carried out as follows:

max

,

where the total amount is the total amount of the amount of insulin bolus initiated by the user, and CR is a given ratio of grams of carbohydrates and units of insulin; after determination of whether the user has entered BG and CHO concentration values into the controller, then, determination of whether the amount of bolus calculated by the system and the amount of insulin bolus initiated by the user are equal amounts or whether the amount of insulin bolus initiated by the user is the adjusted amount of bolus other than the amount of bolus calculated by the system; and the subsequent use of the controller for the determination of a corrective value of the system-oriented residual amount of active insulin, as corresponding to at least one of the component of blood glucose level correction, the food component, and the adjusted amount of bolus. At the same time, if all of BG concentration value, CHO value, and continuous glucose measurement (CGM) value are not available, then, the calculation of the component of blood glucose correction for the amount of insulin bolus initiated by the user, by means of the controller, is carried out as follows: Total amount/2, where the total amount is the total amount of the amount of insulin bolus initiated by the user. A method for the determination of a corrective value for the system-oriented residual amount of active insulin in the system for measuring a glucose level, and a system for accounting for the residual amount of active insulin are also disclosed.

EFFECT: group of inventions provides for accounting for bolus insulin in such a way that system-oriented IOB (SFIOB) supports only and all corrective insulin as accurately as possible, thus ensuring insulin dosing by the system, which is safe and effective.

14 cl, 6 dwg, 6 ex

Description

FIELD OF TECHNOLOGY

[0001] The invention relates essentially to the field of blood glucose monitoring systems, more specifically, to a feedback blood glucose monitoring system, such as an artificial pancreas system, which uses a controller using more than one model to account for the residual amount active insulin.

BACKGROUND OF THE INVENTION

[0002] Diabetes mellitus is a chronic metabolic disorder caused by the inability of the pancreas to produce enough of the hormone insulin, resulting in a decrease in the body's ability to metabolize glucose. This disorder can lead to an excessive concentration of glucose in the bloodstream or to hyperglycemia. Persistent hyperglycemia alone or in combination with hypoinsulinemia is associated with a variety of serious symptoms and life-threatening long-term complications. Currently, the restoration of endogenous insulin production is not yet possible. As a result, therapy is required to maintain blood glucose concentrations within the normal range. This glycemic control is achieved by regularly delivering external insulin to the patient to lower blood glucose levels.

[0003] Significant improvements in the treatment and management of diabetes have been achieved through the development of drug delivery devices that relieve the patient of the need to use syringes or drug pens to administer multiple daily insulin injections. Such drug delivery devices allow insulin to be administered in a manner that is more similar to the naturally occurring insulin release of the human pancreas, and which can be controlled according to different standards or individually modified protocols to provide the patient with more individualized glycemic control.

[0004] Such devices for the introduction of drugs can be made in the form of implantable devices. Alternatively, the device may be an external device with an infusion set for subcutaneous infusion into the patient's body via percutaneous insertion of a catheter, cannula, or transdermal drug delivery device, such as through a patch. External drug delivery devices are mounted on clothing, or more preferably hidden under clothing or within clothing, or mounted on the body, and are typically controlled by a user interface built into the device or provided on a separate remote device.

[0005] To achieve an acceptable level of glycemic control in devices, control of glucose levels in the blood or tissue environment is required. For example, administering an appropriate amount of insulin via a medicament delivery device requires the user to frequently, sporadically, determine their blood glucose level by testing. The level is injected into the pump or controller, after which a suitable modification can be calculated according to the current default insulin protocol ( i.e. dosage and frequency). Such a modification is used to adjust the operation of the drug delivery device accordingly. Alternatively, or in combination with such episodic determinations, continuous glycemic monitoring (CGM) is used with a drug delivery device, which provides feedback control of insulin delivery to a diabetic patient.

[0006] In addition, to provide feedback control, autonomous modulation of the drug administered to the user is provided by the controller using one or more control algorithms. For example, you can use proportional-integral-derivative (PID) control algorithms that respond to observed glucose levels. PID can be tuned based on simple rules of mathematical models of metabolic interactions between glucose and insulin in humans. Alternatively, model predictive controllers (MPCs) can be used. MPC is advantageous because MPC takes into account the effects of changes in control in the near future in advance, and is sometimes subject to limitations in determining the outcome of MPC, while PID generally only includes past results in determining future changes. In MPC, restrictions can be implemented in such a way that a solution in a limited "space", i.e., within the established introduction restrictions, is guaranteed and the system cannot exceed the reached limit.

[0007] Known MPCs are described in the following documents: US Pat. No. 7,060,059; US Patent Publications Nos. 2011/0313680 and 2011/0257627; International Publication WO 2012/051344; Percival et al ., " Closed–Loop Control and Advisory Mode Evaluation of an Artificial Pancreatic Beta Cell: Use of Proportional–Integral–Derivative Equivalent Model–Based Controllers " J. Diabetes Sci. Technol., Volume 2, Issue 4, July 2008; Paola Soru et al ., " MPC Based Artificial Pancreas; Strategies for Individualization and Meal Compensation, " Annual Reviews in Control 36, pp. 118–128 (2012); Cobelli et al ., "Artificial Pancreas: Past, Present, Future" Diabetes Volume 60, November 2011; Magni et al ., " Run-to-Run Tuning of Model Predictive Control for Type 1 Diabetes Subjects: In Silico Trial " J. Diabetes Sci. Techn., Volume 3, Issue 5, September 2009; Lee et al ., " A Closed–Loop Artificial Pancreas Using Model Predictive Control and a Sliding Meal Size Estimator " J. Diabetes Sci. Techn., Volume 3, Issue 5, September 2009; Lee et al ., " A Closed–Loop Artificial Pancreas based on MPC: Human Friendly Identification and Automatic Meal Disturbance Rejection, " Proceedings of the ^17th World Congress, The International Federation of Automatic Control, Seoul Korea, July 6–11, 2008 .; Magni et al., "Model Predictive Control of Type 1 Diabetes: An in Silico Trial" J. Diabetes Sci. Techn., Volume 1, Issue 6, November 2007; Wang et al ., " Automatic Bolus and Adaptive Basal Algorithm for the Artificial Pancreatic β–Cell " Diabetes Techn. Ther., Vol. 12, No. 11, 2010; Percival et al ., " Closed-Loop Control of an Artificial Pancreatic β-Cell Using Multi-Parametric Model Predictive Control, " Diabetes Res. 2008; Kovatchev et al ., "Control to Range for Diabetes: Functionality and Modular Architecture," J. Diabetes Sci. Techn., Volume 3, Issue 5, September 2009; and Atlas et al ., "MD–Logic Artificial Pancreas System," Diabetes Care, Vol. 33, No. 5, May 2010. All articles or documents referenced in this application are hereby incorporated by reference as if they were set out in full in this document.

[0008] Glucose monitoring systems traditionally use a measure of active insulin residual that takes into account all of the bolus insulin delivered without taking into account the difference between insulin given for food-related purposes and insulin given for correction ( i.e. , reducing glucose concentration). In systems where there is no food intake model, two models are proposed to account for active insulin residuals to improve glucose control: patient-centric active insulin residuals and system-centric active insulin residuals. By "patient-specific active insulin residual" or PFIOB is meant active insulin residual, including meal-related insulin and correction-related insulin, but usually excluding basal insulin; a well-known value that is easily understood by patients. By “system-targeted residual active insulin” or SFIOB is meant, in a system without a meal pattern, residual active insulin with the potential to lower glucose concentration, i.e. correction-related insulin; this value excludes both mealtime insulin and basal insulin, neither of which is designed to lower glucose concentrations. The use of these separate models is problematic in that there is a need to separate mealtime insulin from boluses, which may include both mealtime insulin and correction insulin. The systems solve this problem by using accurate therapeutic parameters such as insulin to carbohydrate ratio and insulin sensitivity factor, along with the proper use of a bolus calculator. However, if the system user does not inform the system of food boluses or correction boluses, or skips carbohydrates and/or blood glucose while using the bolus calculator, or increases or decreases the estimated bolus dose without providing the system with justification for the increase or decrease, erroneous increases, decreases may occur. or interruption of insulin administration.

[0009] Thus, there is a need in the art for a diabetes management system that can use a set of rules to overcome this shortcoming.

BRIEF DESCRIPTION OF GRAPHICS

[0010] In FIG. 1 is a schematic view of an embodiment of an artificial pancreas (AP) diabetes management system.

[0011] In FIG. 2 is a diagram of the main part of the AP-based diabetes management system shown in FIG. one.

[0012] In FIG. 3 is a graph of insulin delivery in an embodiment of the AP system following a patient-initiated insulin bolus with no portion of the insulin present as residual active insulin.

[0013] In FIG. 4 is a graph of insulin administration in an embodiment of the AP system following a patient-initiated insulin bolus, with all insulin represented as residual active insulin.

[0014] In FIG. 5 is an insulin delivery schedule for an embodiment of the inventive AP system following a patient-initiated insulin bolus, in which a portion of the insulin is represented as residual active insulin.

[0015] In FIG. 6 is a block diagram of the bolus analysis logic for an embodiment of an AP-based diabetes management system.

DETAILED DESCRIPTION OF THE INVENTION

[0016] A key requirement for the effective implementation of a feedback insulin administration system using a predictive model control (MPC) algorithm is to determine and accurately record the insulin administered to the user, which is currently active in the body and has not yet entered into action, known as the residual amount of active insulin (IOB) in the patient or user. The present invention provides systems and methods for use in systems that account for bolus insulin such that the system-specific IOB (SFIOB) supports as accurately as possible only and all corrective insulin (i.e., insulin given to reduce blood glucose levels), thus ensuring insulin dosing by the system is safe and effective.

[0017] The blood glucose monitoring system of the present invention includes: a glucometer that detects a blood glucose (BG) value for a biological sample; an insulin pump that is in communication with the meter and is programmed to deliver a user-initiated insulin bolus to the user; a controller that is connected to the user interface and includes a processor programmed to: (i) determine if the user has entered a blood glucose value into the user interface, (ii) calculate the correction component, i.e., the bolus component administered for blood glucose lowering, bolus based on blood glucose value; (iii) determining whether the user has entered the amount of carbohydrates into the user interface; and (iv) calculating the bolus components based on the amount of carbohydrates (the food component of the bolus). In the system of the present invention, the SFIOB is then determined based on at least one of the correction component and the food component of the bolus. When a glucose value and a carbohydrate value are not entered into the controller, these components can be calculated based on the last CGM value. If the CGM value is also not available, then one half (50%) of the total insulin bolus is assigned to the SFIOB value.

[0018] The invention also relates to a method for accounting for the residual amount of active insulin in a glucose measurement system, in which a patient-initiated insulin bolus is dispensed, and then a determination is made whether the user enters data into the controller related to the previous blood glucose concentration value, measured by the system. If a previous blood glucose value was entered, then the blood glucose correction component of the bolus is calculated from that value. The second determination is made as to whether the user has entered an input to the controller relating to the amount of carbohydrates. If the amount of carbohydrates was entered, then the food component of the bolus is calculated based on this amount of carbohydrates. A third determination is made as to whether the user has adjusted the user-initiated insulin bolus. The SFIOB is then determined based on at least one of the calculated bolus components and the third determination or adjusted amount. A specified one-half (50%) component of a total meal-related insulin bolus is assigned to the remaining active insulin when the previous blood glucose and carbohydrate counts are not entered into the controller and the last CGM is not available.

[0019] The invention also relates to a blood glucose monitoring system having a sensor that automatically detects a blood glucose value for a biological fluid, and an insulin pump that receives the data received by the sensor and is programmed to administer to the user initiated by the patient or user bolus insulin. The system also includes a controller that communicates with the pump and has a user interface and processor. The processor is programmed to: determine if the user has entered data into the user interface related to the previous blood glucose value measured by the system; calculating a bolus correction component based on the previous blood glucose value; determining whether the user has entered data into the user interface related to the amount of carbohydrates; and calculating the food component of the bolus based on the amount of carbohydrates. The SFIOB value is then determined based on at least one of the components of the bolus. A predetermined corrective component of one half (50%) of the total mealtime insulin bolus is attributed to the remaining active insulin when the previous blood glucose and carbohydrate amount is not entered into the controller and the last CGM is not available.

[0020] As shown in FIG. 1, an artificial pancreas (AP) diabetes management system 100 includes a controller 110 and a drug delivery device or insulin pump 130. The medication delivery device 130 is connected to an infusion set 135 via a flexible tube 134. The controller 110 includes includes a housing 111, a user interface 112, an autonomous modulation (or control) algorithm, which may be any suitable control algorithm, and is preferably an MPC 150 (FIG. 2) and a memory device (not shown). The drug administration device 130 is configured to transmit data to and receive data from the controller 110, for example, via a communication channel 122 such as RF, Bluetooth®, and the like. In one embodiment, the drug administration device 130 is an insulin infusion device or pump, and the controller 110 may be a handheld controller or a user electronic device such as a smartphone, computer, exercise monitor or user device, and the like. In such an embodiment, the data transmitted from the drug delivery device 130 controller 110 may include information such as, for example, insulin delivery data, blood glucose levels, basal/bolus data, insulin to carbohydrate ratio, or insulin sensitivity ratio. Controller 110 may be configured to include a feedback controller programmed to continuously receive glucose readings from CGM sensor 117 over communication channel 123. The data transmitted from the controller 110 to the administering device 130 may include glucose measurements and a food database so that the administering device 130 can calculate the amount of insulin to be administered. Alternatively, controller 110 may perform basal or bolus calculations and send the results of such calculations to device 130 for administering medication. Bolus advice may be performed manually upon triggering by the subject, or may be automated such that the system is capable of administering insulin delivery in both bolus and basal modes.

[0021] As shown in FIG. 1, a glucometer 160 ( e.g. , an episodic blood glucose meter), alone or in combination with a CGM sensor 117, provides data to the controller 110 and/or administering device 130, e.g. , via appropriate communication channels 123, 124. The meter 160 may measure the fluid sample placed on the test strip 170. The controller 110 may present information and receive commands through a user interface, such as the touch screen 113 shown, or other devices.

[0022] The controller 110, the drug delivery device 130, and the CGM sensor 117 may be integrated into multi-functional blocks in any combination. For example, controller 110 may be integrated into drug delivery device 130 to form a combined single body device. Infusion, sensory and control functions can also be integrated into a one-piece artificial pancreas. In various embodiments, the controller 110 is combined with the glucometer 160 into a complex one-piece device having a housing. In other embodiments, controller 110 and meter 160 are two separate devices that can be connected to each other to form a complex device. Devices 130, 110, and 160 each have a suitable microprocessor (not shown for brevity) programmed to perform various functions.

[0023] The administering device 130 or controller 110 may also be configured to communicate bi-directionally with a remote health monitoring station via, for example, communication network 119. One or more servers 128 or storage devices 126 may be communicatively coupled to controller 110 via network 119. In one example, administering device 130 and/or controller 110 may communicate with personal computer 127 over a communication channel such as radio frequency. channel, Bluetooth®, and the like. The controller 110 and the remote station may also be configured for two-way wired communication via, for example, a communications network based on a landline telephone. Examples of remote monitoring stations may include, but are not limited to, a personal or network computer 127, a server 128, a storage device 126, a personal digital assistant, another mobile phone, a hospital monitoring station, or a dedicated clinic remote monitoring station. Alternatively, although not shown in FIG. 1, data storage may be further provided in the cloud.

[0024] As shown in FIG. 1, the controller 110 also includes a user interface 112. As shown, the user interface 112 has a display screen 113 and one or more function buttons 115 that allow the user to turn the controller 110 on and off, as well as manually enter data and select various functions of the controller 110. In one embodiment, the user interface 112 may also include an audible alarm, vibrator, or voice prompt to notify the user of a particular operating condition or request data from the user. In another embodiment, the user interface 112 includes a touch screen display in addition to one or more function buttons.

[0025] The control algorithm may reside in the remote controller 110 and/or in the drug delivery device 130 in the configurations shown in FIG. 1. In one configuration, the controller 110 will wirelessly collect the necessary information ( eg , insulin administration history) from the drug administration device 130 as well as from the glucose sensor 117 ( eg , glucose data) to allow the drug administration device 130 to means using the control algorithm to calculate the amount of insulin to be modulatively administered by the drug administration device 130 . Alternatively, controller 110 includes a control algorithm and can perform a basal or bolus calculation and send the results of such calculations along communication channel 122 with administration instructions to device 130 for administering medication. In an alternative embodiment, the episodic blood glucose meter 160 and biosensors 170 may also be used alone or in combination with CGM sensor 117 to provide blood glucose data to controller 110 and/or administering device 130.

[0026] According to one embodiment, controller 110 further includes an MPC 150 (FIG. 2) that is programmed to receive continuous data from CGM sensor 117 via transmitter 118 coupled to CGM sensor 117 and over communication channel 123. The transmitter 118 transmits data received from the CGM sensor 117 related to the concentration of glucose in the user's interstitial fluid. In another embodiment, controller 110 receives data from a CGM receiver located in drug administration device 130 over communication channel 122. Controller 110 may process the received data and transmit additional data to drug administration device 130, which may include data related to glucose measurements and a food database. The medicament delivery device 130 may use the data received from the controller 110 to calculate the amount of insulin to be administered to the user at a given time. The controller 110 may also perform a basal rate or insulin bolus calculation and communicate such calculations to the medication delivery device 130.

[0027] In one embodiment, controller 110 receives signals from transmitter 118 connected to CGM glucose sensor 117 over communication channel 123. The controller 110 has a central processing unit (CPU) programmed to perform various functions and calculations. The MPC 150 (FIG. 2) is programmed to use the data received from the CGM sensor 117 to determine, on one occasion, the appropriate amount of insulin to administer to the user at predetermined periodic intervals. Controller 110 then transmits dosing commands to drug delivery device 130, which injects the calculated amount of insulin through infusion set 135. Interstitial fluid glucose concentration can be related to blood glucose concentration such that the user does not need to perform a lot of finger manipulation. Because controller 110 is programmed to receive data from CGM transmitter 118 or receiver (not shown), controller 110 can also be programmed to approximate blood glucose values using the data, as well as predict blood glucose trends and blood glucose rate of change. over time.

[0028] As shown in FIG. 1, the meter 160 further includes a meter user interface 166, which may include one or more function buttons 168 and a display screen 169. In a further embodiment, the display screen 169 may have touch screen capabilities. Test strip port 162 is configured to receive an electrochemical test strip or biosensor 170. Electrochemical test strip 170 is configured at one end to respond to a biological sample, such as blood, with a reagent and establish an electrical connection to a glucometer 160 at the opposite end. .

[0029] As shown in FIG. 2, the MPC 150 accesses the glucose concentration data acquired by the CGM sensor 117 or (and preferably) the glucometer 160 (FIG. 1) and calculates a correction bolus value that will be transmitted to the drug administration device 130 from which the calculated value will be administered to the user. bolus. In one embodiment, the glucose concentration is obtained from the glucometer via communication channel 126. The controller 110 may also include a memory device (not shown) that is in communication with the MPC 150. The memory device (not shown), which may include volatile and non-volatile memory, may store a set of blood glucose values and other related data that the MPC 150 can access to calculate blood glucose trends and mean blood glucose values over a predetermined period of time and at predetermined time intervals. In accordance with one embodiment, the predetermined time interval is 5 (five) minutes. In one embodiment, the memory device stores predetermined information related to the user's insulin sensitivity factor (ISF), carbohydrate ratio (CR), target blood glucose (T), and other predetermined metabolic parameters. The memory device may include both volatile and non-volatile memory. The MPC 150 is programmed to automatically adjust the rate of insulin delivery to the user based on the glucose measurement provided by the CGM sensor 117, the data entered by the user, and any parameters stored in the memory device at each predetermined time interval.

[0030] The drug administration device 130 further includes a CPU and a CGM receiver. The CPU is programmed to deliver the appropriate dose of insulin based on commands received from the controller 110. The CGM receiver is programmed to receive data from the transmitter 118 and transmit or relay said data to the controller 110. In one embodiment, the administering device 130 has one or more function buttons or dials 136 that allow the user to enter data into the drug delivery device 130. The drug administration device may also include a drug administration display screen 140 that relays visual information to the user, the display screen 140 may have touch screen capabilities. User input to drug delivery device 130 may include programming a patient-initiated insulin bolus.

[0031] Glucose sensor 117 is an electrochemical sensor that measures the concentration of glucose in the user's interstitial fluid at predetermined time intervals and transmits this data back to the controller 110 (or a CGM receiver housed in a separate administering device 130) via a transmitter 118. Concentrations blood glucose can be approximated using data received by the glucose sensor 117 and transmitted via the transmitter 118 to the controller 110 or CGM receiver located in a separate device 130 for drug administration. The controller 110 receives information from the transmitter 118 and calculates the proper dose of insulin to administer to the user and transmits these dosing commands to the medicament delivery device 130. The controller 110 can also transmit and receive data over the communication network 119 such that data related to the user's therapy can be accessed by healthcare professionals or other individuals or entities over the Internet or any other information network.

[0032] As shown in FIG. 2, the first output 151 of the MPC 150 may be commands to the insulin pump or administering device 130 to administer the desired amount of insulin 154 to achieve the desired glucose concentration in the user's body at the next predetermined time (and such time intervals may be, for example, five minutes). As noted, the glucose sensor 117 measures the glucose levels in the user's interstitial fluid, and this information is used to estimate the user's actual blood glucose level.

[0033] The logic circuit described above and shown schematically in FIG. 2 is based on predicted glucose concentration levels based on previous information entered into the AP system 100 (FIG. 1) through communication with other components of the AP system 100 or a user. If the required information is not available, the MPC 150 cannot provide accurate predictions and therefore may lead to incorrect corrections or settings of the drug delivery device 130. For example, existing AP systems having a model-based predictive control algorithm do not accurately analyze food-related IOBs as compared to correction-related IOBs, leading to fundamentally mispredicting future blood glucose concentrations.

[0034] There are currently 3 (three) recognized ways to calculate IOB after administration of a patient-initiated insulin bolus: (1) classify none of the insulin boluses as IOB; (2) classify the entire insulin bolus as IOB; or (3) classify one half (50%) of the insulin bolus as an IOB. However, the present invention provides a method for more accurately determining or classifying the amount of insulin bolus needed to correct carbohydrate intake (CHO) and the amount needed to correct suboptimal blood glucose (BG).

[0035] Method 1, as shown in FIG. 3 is characterized in that the user administers an insulin bolus 300 in conjunction with a meal and does not report its MPC 150 (FIG. 2) as an IOB. Accordingly, the AP system 100 (FIG. 1) does not take into account the insulin bolus 300 and therefore does not predict a decrease in blood glucose concentration in the near future 310 after the administration of the insulin bolus 300 and provides an incorrect prediction for the AP system 100 (FIG. 1). The term "near future" or "post-injection period" is defined as the period of time immediately following the administration of an insulin bolus 300 during which absorption of the appropriate food has a significant effect on glucose concentration. The prediction provided by MPC 150 (FIG. 1) for system 100 (FIG. 1) will be an overestimate of the amount of insulin to be delivered by drug delivery device 130 (FIG. 1) in the post-administration period. Accordingly, adjusting or adjusting the user's insulin delivery as determined by the system will not result in a proper decrease in insulin delivery and may result in an insulin-induced hyperglycemic event because the user is administering too much insulin and their blood glucose levels fall below the predetermined range or target value. As shown in FIG. 3, system insulin delivery is still high in the near future 310 after an unreported insulin bolus.

[0036] Method 2, as shown in FIG. 4 is characterized in that the user administers an insulin bolus of 400 in conjunction with a meal and reports the entire insulin bolus of 400 MPC 150 (FIG. 2) as IOB. However, only a portion of the insulin bolus 400 is the nutritional component needed to correct carbohydrate intake, while the other portion is used for the correction component to correct the user's blood glucose in the normal mode. Thus, MPC 150 (FIG. 2) recognizes an artificially high SFIOB value and predicts a sharp drop in blood glucose during period 410 after administration. Therefore, the modification of the user's basal insulin delivery provided by the AP system 100 (FIG. 1) will mean a reduction (or even suspension) of insulin delivery in the near future after the administration of insulin bolus 400. This will cause the user's blood glucose levels to rise above T and may cause a hyperglycemic event. As shown in FIG. 4, the near future insulin delivery 410 by the system drops significantly after the reported insulin bolus 400. It can also be seen that the amount of insulin delivered in the near future 410 fluctuates, corresponding to fluctuations in the user's blood glucose levels, as the system 100 (FIG. 1) trying to restore basal levels of insulin delivery.

[0037] Method 3 classifies one half (50%) or some other specified percentage of a patient-initiated insulin bolus as an IOB. However, system 100 (FIG. 1) may still deliver much more or less insulin than is required to maintain the user's blood glucose control during the post-infusion period. Accordingly, the user will still experience a higher incidence of sub-optimal glucose levels than when using the described method. The results of each alternative method are compared with the results of the present method in examples 1-6, which are discussed in more detail below.

[0038] The current AP system 100 (FIG. 1) utilizes an MPC 150 (FIG. 2) programmed to account for SFIOB to prevent the significant increases and decreases in blood glucose that occur in the systems shown in FIG. 3 and 4 previously described. As shown in FIG. 5, the MPC 150 (FIG. 2) is programmed to classify only the portion of the insulin bolus 500 administered to the user as SFIOB, and therefore only considers that fraction of insulin when predicting near-future glucose levels 510. When comparing near-future insulin delivery 310 , 410 and 510 from the systems shown in FIG. 3-5, insulin delivery after administration at step 510 is more regulated and lies between the levels seen at step 310 (which would possibly lead to a hypoglycemic event) and step 410 (which would probably lead to a hyperglycemic event).

[0039] The MPC 150 (FIG. 2) determines what data has been received from other parts of the system 100 (FIG. 1) and what assumptions, if any, must be made in order to classify a portion of a patient-initiated insulin bolus as attributed to SFIOB. As shown in block diagram 600 of FIG. 6, a patient-initiated bolus is delivered at step 602. At step 604, the algorithm then determines if a BG value is available, either manually entered by the user or automatically transmitted by the meter over communication channel 126 (FIG. 1). After the MPC 150 (FIG. 2) determines if a BG value is available, the MPC then determines if a CHO has been output by the user at 608. The CHO value corresponds to an estimate of the amount of carbohydrate in the food the user is about to take or is currently taking.

[0040] If the BG value is available while the carbohydrate amount is not available, then the amount of insulin to correct the high BG level or the amount of insulin to correct the BG is determined in step 606 using the following formula:

(one)

where "min." is the minimum function;

"Max." is the maximum function;

"total" is a total bolus; "target value" is the target glucose value for the patient; and

The ISF is the patient's insulin sensitivity factor.

[0041] If the CHO value is provided by the user while the BG value is not available, then the amount of insulin to correct the high BG level is calculated at 610 using the following formula:

(2) max.

where CR is the user's carb ratio.

[0042] If both the BG value and the CHO value are present, the amount of insulin to correct is calculated in step 612 using the following formula:

(3)

[0043] It is advantageous if the amount of insulin administered to the user is slightly lower to prevent insulin-induced hypoglycemic events. For example, if there are two or more IOB calculation methods, the method that gives the larger amount will cause the MPC 150 (FIG. 2) to provide a more predictive lower blood glucose for point A. As a result, the controller 110 (FIG. 1) suggest a more conservative insulin regimen or corrective component in the near future (i.e. administering less insulin than may be needed).

[0044] If neither the number of BGs nor the number of CHOs has been received, the CGM value may be replaced at step 614 for the BG. The resulting correction value for SFIOB is then determined using the following relationship:

(four)

[0045] If CGM data is also unavailable, the algorithm reverts to the 50%/50% approach and calculates an estimated correction using the following ratio (block 616 shown in FIG. 6):

(5)

The following examples are provided to demonstrate the described methodology:

Examples

Example 1

[0046] The following values are set and stored in a memory device (not shown) of the drug administration device 130:

The user's CR is 10 grams per unit of insulin;

The user's ISF is 50 mg/dL per unit of insulin;

The user's blood glucose target is 120 mg/dL; and

The current value of PFIOB is 0.

[0047] According to this example, the user did not enter a blood glucose (BG) value, but provided an estimate of the amount of carbohydrate received from a meal as 20 g. The MPC 150 (FIG. 2) calculates the amount of CHO insulin as follows:

= 2 единицы инсулина

= 2 units of insulin

[0048] However, the user then manually increases the dose to 3 units of insulin. The controller 110 is programmed in such a way that it believes that the user will estimate the amount of carbohydrates entered by him as correctly as possible. Thus, the MPC 150 (FIG. 2) can correctly deliver 2 units of insulin, given the increase in glucose that is expected after a user consumes 20 g of carbohydrates. In this case, the algorithm determines the corrective insulin, which is the difference between the total bolus amount and the carbohydrate bolus calculated by the controller based on the amount of carbohydrate entered by the user.

Correction: entered 3 units - calculated 2 units = 1 unit

[0049] Thus, MPC 150 (FIG. 2) classifies 1 (one) unit of insulin as a correction component for correcting the user's BG value and 2 (two) units of insulin as a food component for a meal. Accordingly, only one unit of insulin is classified as SFIOB for the future and is considered by the MPC 150 (FIG. 2) when predicting glucose concentration for insulin administration in the near future or in the post-administration period. This result can be compared with Methods 1-3 discussed earlier and examples of which are shown in FIG. 3–5. As shown below, the use of any of the previous methods leads to the introduction of insulin below the optimal or above the optimal amount in the near future compared to the claimed method.

Method 1 Method 2 Method 3 The claimed method 0 units 3 units 1.5 units 1 unit

Example 2

[0050] Using the same stored parameters as in example 1, the user again estimates that the carbohydrate intake is 20 g. As in example 1, the controller 110 calculates that 2 (two) units of insulin are CHO insulin and should be administered user to account for the CHO value. However, in this case, the user reduces the bolus from 2 (two) units to 1 (one) unit.

Correction: entered 1 unit - calculated 2 units = -1 unit

[0051] The received bolus is a negative number, which means that no part of the insulin to be administered to the user will be classified by the MPC 150 (FIG. 2) as a correction, since the amount of insulin cannot be less than zero. As shown below, only method 1 assigns the same number of units of insulin as SFIOB for purposes of predicting MPC 150 (FIG. 2) glucose levels in the near future compared to the claimed method.

Method 1 Method 2 Method 3 The claimed method 0 units 1 unit 0.5 units 0 units

Example 3

[0052] Using the same stored information as in Examples 1 and 2, the user enters a BG value of 270 mg/dL into the controller and does not enter a CHO value. The MPC 150 (FIG. 2) defines corrective BG insulin as follows:

единицы инсулина

units of insulin

[0053] The user then manually increases the total bolus to five (5) units of insulin. The MPC 150 (FIG. 2) is programmed to believe that the user has correctly determined the blood glucose value entered into the controller 110. Thus, the MPC 150 (FIG. 2) can correctly deliver 3 (three) units of insulin, which are a corrective component for correcting elevated blood glucose levels of the user. In this case, the correction value is the minimum value between the total bolus (5 units) and the correction component based on the user-entered BG value (3 units):

Correction: min. (total 5 units, calculated 3 units) = 3 units

[0054] The 2 (two) units of insulin do not count towards the MPC 150 (FIG. 2) for the future because the system considers that the user has increased the total dose for the purpose of possible carbohydrate intake and has scheduled correction only in accordance with the BG value entered by the user (or the value BG transmitted wirelessly by the meter). As shown below, the use of any of the previous methods leads to the introduction of insulin below the optimal or above the optimal amount in the near future compared to the claimed method.

Method 1 Method 2 Method 3 The claimed method 0 units 5 units 2.5 units 3 units

Example 4:

[0055] Using the same stored information as in Examples 1-3 and the same BG value as in Example 3, the user then manually reduces the total bolus to be delivered to 1 (one) unit of insulin. The MPC 150 (FIG. 2) is programmed to believe that the user has correctly determined the blood glucose value entered into the controller 110. However, since the total bolus amount is 1 (one) unit of insulin, the MPC 150 (FIG. 2) can only classify 1 (one) unit as a correction component, not the calculated 3 correction units calculated based on BG value, CF value and user target value. In this example, only method 2 classifies the same number of units of insulin as a correction for the purposes of predicting MPC 150 (FIG. 2) glucose levels in the near future compared to the claimed method.

Method 1 Method 2 Method 3 The claimed method 0 units 1 unit 0.5 units 1 unit

Example 5

[0056] Using the same stored information as in the examples above, the user enters a BG value of 170 mg/dL and a carbohydrate value of 20 g. The MPC 150 (FIG. 2) determines the corrective BG insulin as follows:

– 0=1 единица инсулина

– 0= 1 unit of insulin

[0057] MPC 150 (Fig. 2) determines the amount of CHO insulin as follows:

= 2 единицы инсулина

= 2 units of insulin

[0058] Based on the above calculations, the total insulin bolus determined by the MPC 150 (FIG. 2) is 3 (three) units. However, in this example, the user increases the total bolus amount from 3 (three) units to 5 (five) units. The MPC 150 (FIG. 2) defines the correction component as the maximum value between the correction calculated from BG and CF, which is 1 unit, and the difference between the total insulin bolus (5 units) and the calculated amount of CHO insulin (2 units), which is 3 units. These 3 (three) units of insulin are classified as SFIOBs moving forward into the future and are taken into account when the system predicts the glucose concentration for post-dose insulin administration purposes. In this example, neither method classifies the same number of units of insulin as a correction for purposes of predicting MPC 150 glucose levels in the near future compared to the claimed method.

Method 1 Method 2 Method 3 The claimed method 0 units 5 units 2.5 units 3 units

Example 6

[0059] Using the same stored information as in the examples above, the user enters a BG value of 220 mg/dL and a carbohydrate value of 20 g. MPC 150 (FIG. 2) determines the BG correction as follows:

– 0=2 единицы инсулина

– 0= 2 units of insulin

[0060] The MPC 150 (FIG. 2) quantifies CHO insulin as follows:

= 2 единицы инсулина

= 2 units of insulin

[0061] Based on the above calculations, the total insulin bolus determined by the MPC 150 (FIG. 2) is 4 (four) units. In this example, the user reduces the bolus amount from 4 (four) units to 3 (three) units. Because the user has entered a BG value, the algorithm assumes that this BG value is accurate and classifies 2 (two) units as a correction component for the future, and this value is taken into account when the system predicts the glucose concentration for insulin administration targets during the post-dose period. As shown below, the use of any of the previous methods leads to the introduction of insulin below the optimal or above the optimal amount in the near future compared to the claimed method.

Method 1 Method 2 Method 3 The claimed method 0 units 3 units 1.5 units 2 pieces

[0062] Additional embodiments include any of the embodiments described above and described in all applications and other materials presented herein, where one or more of their components, functionality, or structures are interchanged, replaced, or supplemented by one or more components, functionality, or structures of another embodiment described above.

[0063] It should be understood that various changes and modifications to the embodiments described herein will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the spirit and scope of the present disclosure and without diminishing its intended benefits. Thus, such changes and modifications are intended to be covered by the appended claims.

Claims (71)

1. A method for accounting for the residual amount of active insulin in a system for measuring glucose levels, and the system includes a controller, the method includes the following steps, which are: calculation of the amount of bolus calculated by the system; after calculating the system-calculated bolus amount, administering the user-initiated insulin bolus amount to the user; after administering the user-initiated bolus amount, determining whether the user has entered a blood glucose concentration (BG) value into the controller; after determining whether the user has entered a BG concentration value into the controller, it is determined whether the user has entered a carbohydrate (CHO) value into the controller; if it is determined by the controller that the user has entered the BG concentration value into the controller but has not entered the CHO value, then the calculation of the blood glucose correction component for the user-initiated insulin bolus amount based on the BG concentration value by the controller as follows:

where total is the total amount of the user-initiated insulin bolus amount, target is the blood glucose target, ISF is the target insulin sensitivity factor, and PFIOB is the patient-oriented active insulin residual; if it is determined that the user has not entered a BG concentration value into the controller, but has entered a CHO value, then calculate, using the controller, the food component for the user-initiated insulin bolus amount as follows: Max.

where total is the total amount of the user-initiated insulin bolus amount and CR is the target ratio of carbohydrate grams and units of insulin; after determining whether the user has entered BG and CHO concentration values into the controller, then determining whether the system-calculated bolus amount and the user-initiated insulin bolus amount are equal amounts, or whether the user-initiated insulin bolus amount is a corrected bolus amount different from the system-calculated bolus amount; and subsequently using the controller to determine a correction value of the system-oriented active insulin residual as corresponding to at least one of the blood glucose correction component, the food component, and the adjusted bolus amount, and moreover, if all of the BG concentration value, CHO value, and continuous glucose measurement (CGM) value are not available, then calculation of the blood glucose correction component for a user-initiated insulin bolus amount, via the controller, as follows: Total / 2 where total is the total amount of the user-initiated insulin bolus amount. 2. The method of claim 1, further comprising, if it is determined that both the BG concentration and the CHO concentration have been entered, then calculating the blood glucose correction component of the user-initiated insulin bolus amount, by the controller, as follows : Max.

where total is the total amount of the user-initiated insulin bolus amount, target is the target blood glucose, ISF is the target insulin sensitivity factor, and CR is the target ratio of carbohydrate grams to units of insulin. 3. The method of claim 1, further comprising, if it is determined that neither the BG concentration nor the CHO values are entered, then calculating the blood glucose correction component of the user-initiated insulin bolus amount based on the (CGM) value of the continuous glucose measurements, by means of a controller, as follows:

, where total is the total amount of the user-initiated insulin bolus amount, target is the blood glucose target, CGM is the continuous glucose measurement, ISF is the target insulin sensitivity factor, and PFIOB is the patient-focused residual amount of active insulin. 4. The method of claim. 1, in which the value of the target blood glucose concentration is set by the controller and stored in the memory device of the controller. 5. The method of claim 1, wherein the predetermined insulin sensitivity factor is stored in a memory component of the controller. 6. The method of claim 1, wherein the user manually adjusts the user initiated insulin bolus amount. 7. A method for determining a correction value for a system-oriented residual amount of active insulin in a system for measuring glucose, the method comprising the following steps: administering a user-initiated insulin bolus amount to a user via the pump, wherein the user-initiated insulin bolus amount can be manually adjusted by the user; after administering the user-initiated insulin bolus amount to the user, determining whether the system controller has received data from the pump related to the blood glucose concentration (BG) value; after determining whether the controller has received data from the pump related to the BG concentration value, determining whether the system controller has received data related to the carbohydrate (CHO) value; if the controller received data from the pump related to the BG concentration value and did not receive data related to the CHO value, then the calculation of the blood glucose correction component, by the controller, is as follows:

where total is the total amount of the user-initiated insulin bolus amount, target is the blood glucose target, ISF is the target insulin sensitivity factor, and PFIOB is the patient-oriented active insulin residual; if the controller has not received data from the pump related to the BG concentration value and has received data related to the CHO value, then the controller calculates the food component for the user-initiated insulin bolus amount based on the CHO value as follows: Max.

where total is the total amount of the user-initiated insulin bolus amount and CR is the target ratio of carbohydrate grams and units of insulin; and then determining, using the controller, a correction value system-oriented residual amount of active insulin as corresponding to at least the blood glucose correction component and the food component for the user-initiated insulin bolus amount, if BG or CHO concentrations are not available, then calculate the blood glucose correction component for the user-initiated insulin bolus amount, via the controller, as follows:

where total is the total amount of the user-initiated insulin bolus amount, CGM is the continuous glucose measurement value, target is the blood glucose target, ISF is the target insulin sensitivity factor, and PFIOB is the patient-focused residual amount of active insulin. 8. The method of claim 7, further comprising determining if the user has corrected the user-initiated insulin bolus amount by the adjusted amount, and determining, using a system oriented controller, the remaining amount of active insulin based on at least one of the glucose correction component in the blood, the food component, and the adjusted amount of the user-initiated insulin bolus amount. 9. The method of claim 7, wherein the continuous glucose measurement (CGM) value is used, by the controller, for the blood glucose correction component if the BG and CHO concentration values are not entered into the controller. 10. The method of claim 7, further comprising, if both BG and CHO concentrations are entered, calculating the blood glucose correction component of the user-initiated bolus amount by the controller as follows:

where total is the total amount of the user-initiated insulin bolus amount, target is the target blood glucose, ISF is the target insulin sensitivity factor, PFIOB is the value of the patient-targeted residual amount of active insulin, and CR is the target the ratio of grams of carbohydrates to units of insulin. 11. The method of claim 9, further comprising, if none of the concentration BG, CHO, and CGM values are available, then calculate the correction component of the user-initiated insulin bolus amount by the controller as follows: Total / 2 where total is the total amount of the user-initiated insulin bolus amount. 12. The method of claim 10, wherein the blood glucose target and insulin sensitivity factor are setpoints stored in the controller. 13. A system for accounting for the residual amount of active insulin, comprising: a sensor located subcutaneously in the user's body; a drug administration device configured to communicate with the sensor and programmed to administer a user-initiated insulin bolus amount to the user; and a controller configured to communicate with the drug administration device, the controller comprising: user interface, and a processor coupled to the user interface and configured to calculate a user-initiated insulin bolus amount, the processor being programmed to: first, determining whether the user has entered data into the user interface related to the blood glucose concentration (BG) value measured by the glucose management system, then determining whether the user has entered into the user interface data related to the value of carbohydrates (CHO); then calculating the blood glucose correction component of the user-initiated insulin bolus amount based on the blood glucose concentration value, if it is first determined that the user entered data related to the glucose concentration (BG) value, but did not enter data related to the CHO value , in the following way:

total is the total amount of the user-initiated insulin bolus amount, target is the blood glucose target, ISF is the target insulin sensitivity factor, and PFIOB is the patient-oriented residual active insulin; then calculate the food component for the user-initiated insulin bolus amount based on the CHO value, if it is first determined that the user entered data related to the CHO value, but did not enter data related to the glucose concentration (BG) value, as follows: Max.

where total is the total amount of the user-initiated insulin bolus amount and CR is the target ratio of carbohydrate grams and units of insulin; then determining the correction value of the system-oriented residual amount of active insulin as corresponding to at least one of the components of the user-initiated insulin bolus amount, where it is determined that neither BG concentration nor CHO values are entered, then calculating the blood glucose correction components for the user-initiated insulin bolus amount based on the continuous glucose measurement (CGM) value, by the controller, as follows:

where total is the total amount of the user-initiated insulin bolus amount, target is the blood glucose target, CGM is the continuous glucose measurement, ISF is the target insulin sensitivity factor, and PFIOB is the patient-focused residual the amount of active insulin, and wherein a predetermined percentage value of the total insulin bolus is assigned to the system-oriented residual amount of active insulin when the BG concentration value and the CHO value are not entered into the controller and the CGM value is not available, and the blood glucose correction component of the user-initiated insulin bolus amount is calculated as follows: Total / 2 where total is the total amount of the user-initiated insulin bolus amount. 14. The blood glucose monitoring system of claim 13, wherein the processor is further programmed to determine whether the user has increased the user-initiated insulin bolus amount by an adjusted amount, and to determine the system-oriented residual amount of active insulin based on at least one of a blood glucose correction component, a nutritional component, and an adjusted amount of the user-initiated insulin bolus amount.

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