WO2014072823A2

WO2014072823A2 - Device for blood glucose level determination

Info

Publication number: WO2014072823A2
Application number: PCT/IB2013/003022
Authority: WO
Inventors: Yakov Benediktovich Ulanovsky; Aleksandr Mihaylovich FROLOV; Alena Yakovlevna KOZLOVA; Maksim Aleksandrovich FATKIN
Original assignee: Scienmet La, Inc.
Priority date: 2012-11-06
Filing date: 2013-11-01
Publication date: 2014-05-15
Also published as: WO2014072823A3; RU2510023C1

Abstract

This invention relates to the field of medicine, and may be used to determine and control the level of biochemical parameters in the blood of patients with a variety of disorders, in particular blood glucose level. A device is claimed to determine blood glucose concentration comprising a line for glucose level measurement by human voice and a line for invasive blood glucose level measurement.

Description

Device for glucose blood level determination

FIELD OF THE INVENTION

This invention relates to the field of medicine, more specifically to endocrinology, and may be used to control glucose concentration in blood in patients with carbohydrate metabolism disorders, to conduct differential diagnostics for insulin-dependent and non-insulin-dependent types of diabetes mellitus, and to determine the state of the disease compensation.

STATE OF THE ART

Diabetes mellitus is a chronic disease that originates as a result of insufficient production of insulin by the pancreas or ineffective receptiveness of the cells of the patient to produced insulin.

Diabetes mellitus is a very widespread disease; the number of people suffering from that malaise grows by the year. Today, over 300 million people on Earth have diabetes mellitus.

Diabetes mellitus requires on-going control of glucose level in the blood, otherwise the disease may lead to serious complications. Only if glucose concentration in the blood is maintained within norm (3.5-6.0 mmol/1), it is possible to forestall the development of complications. Following correct nutrition and physical activity regimens and maintaining a normal or close to normal glucose concentration in the blood makes it possible to prevent the development of diabetic complications.

A blood sugar test, where it is necessary to obtain a drop of blood as a sample, is widespread. For that purpose, special automatic devices are used to puncture the skin. The determination of sugar level is performed at the laboratory. The known methods of performing blood analysis for sugar content in the blood of a patient are based on the property of blood sugar to reduce certain salts in the process of complex chemical reactions; such analyses are biochemical in nature.

The blood for analysis for glucose content is taken by a variety of methods: from a vein (venipuncture), by puncturing the skin of fingertips or ear lobe. In the first case, venous blood is analyzed, while in the second case it is capillary blood. Such method of diagnostics is very informative for the attending doctor and very reliable. However, it can be provided only in specially equipped medical centers by skilled personnel.

A method and device are known for the determination of glucose concentration in human blood and continuous monitoring of glucose concentration in human blood (RU 2342071 , 2007). The method consists in measuring the transmitting functions with the help of two pairs of four- electrode sensors fastened on the surface of the human body. A disadvantage of the method is low sensitivity to glucose concentration determination, since glucose is electrically neutral. Its concentration in the blood is three orders less than concentration of electrolytes in the blood and in biotissues.

A non-invasive method and device are known for the determination of glucose concentration in human blood, comprising the measurement of systolic and diastolic arterial blood pressure consecutively on the left and right arms of the patient, glucose blood content being calculated according to mathematical formulae (RU 2368303, 2007).

However, that method is too complex and not accurate enough, since it requires each time to measure blood pressure on both arms of the patient during fasting and after food intake, while glucose concentration in blood is calculated according to mathematical formulae proposed by the applicant.

At the present time, portable devices have been designed for blood sugar determination that may be used by patients at home for determining their blood sugar levels by themselves. That is necessary to correctly adjust the drug dosage for diabetic patients, which significantly increases the efficacy of treatment. All kinds of glucometers can be found on the market today.

The disadvantage of such devices consists in the fact that they are expensive, require disposable materials (test strips) to be purchased for them, and, most important of all, require a blood sample to be taken. In doing so, there is a likelihood of injuring and infecting the patient.

It is known that researchers from Israel and the USA have developed a method of early Parkinson's disease diagnostics, based on the assessment of the finest changes of the human voice, according to The Daily Telegraph. At this time, Parkinson's disease is diagnosed, as a rule, only after the quantity of dead motor neurons has become sufficiently large to cause such symptoms as muscular rigidity, tremor and impaired balance.

Treatment begun at that stage may slow down the disease progression, but not restore movement functions. Timely diagnostics, according to the researchers, may prevent the destruction of up to 60 percent of the nerve cells of the respective brain areas.

It is also known that Parkinson's disease affects larynx muscle functions, which sooner or later results in voice hoarseness.

Attempts of early Parkinson's disease diagnostics based on changes of the voice had been undertaken earlier, but were unsuccessful. Professor Shimon Sapir of the University of Haifa managed to accomplish it by using an alternative approach to voice analysis and developing special computer software that identifies changes characteristic of the disease even before they become discernible by the ear. It needs to be said that the voice itself, irrespective of the words being said, contains a colossal amount of information; the voice allows determining the character of a person and many other things.

It may be attributed to the fact that the voice is directly connected to the anatomy and physiology: it depends on the body structure in general and the structure of voice-generating organs, in particular. Sounds are generated during fluctuation of vocal folds, which are stretched in the larynx like strings. They can perform from 80 to 10,000 and more fluctuations in a second, vibrating either with all its mass or with individual portion thereof. It has been established that, under the influence of nerve impulses coming from the central nervous system, the voice folds change their length, thickness and degree of tension. It is the contraction of various portions of the folds that gives rise to the richest array of sounds, similar to the guitar strings when pressed in different places giving rise to different notes.

As noted above, the voice is related to the anatomy and physiology, therefore almost any disease, in one way or another, influences the way the voice sounds. The voice changes in case of such diseases as bronchitis, tonsillitis, or sinusitis.

A sophisticated electro-acoustic processing of the human voice pronouncing phrases expressing a variety of emotions - joy, grief, fear or anger - has shown that each state of the human being is characterized with a set of distinctive acoustic features. For example, the state of grief is characterized with the greatest length of a syllable, specific ""ascents" and "descents" in the pitch; fear is characterized with sharp fluctuations of the voice volume, distortions of speed and rhythm of the speech, increased pauses etc.

Thus, the voice conveys very accurate information to the surrounding people about the current state of a person. Such reactions are usually poorly controlled by the person himself, so they are very informative.

As the emotional state of a person changes, a great number of his speech characteristics also uncontrollably change.

At the present time, devices are known of the determination of the psycho-emotional state of a person based on the relationship of the ongoing psychic processes with the dynamics of physiological processes; this is made use of, e.g., in the so-called "lie detectors".

Moreover, parameters of the state of a person may be recorded with the help of external devices not connected directly to the person in question.

That said, parameters of sound fluctuations of the human voice may change not only in the case of change in the emotional state, but due to physiological changes of the larynx and vocal cords, given a change in biochemical properties of the human blood, e.g., a change in the blood glucose level.

According to research, if there is a change in blood glucose level, including the blood flowing in the larynx and the cords, there will occur changes in the elastic properties of the biological tissue of these organs, which in turn will result in changes in spectral characteristics of sound fluctuations of the human voice (which complies with Hooke's law of physics).

Thus, a theoretical analysis of the spectrum of fluctuations of a 2D plate shows that, due to a change in the plate material elasticity ratio, there occurs a change in the spectral composition of plate fluctuations. There occur new overtones, shifts in frequency peaks and changes of intensity of a number of peaks in the fluctuation spectrum. All those changes in the spectrum may be used as quantitative metrics of the change in corresponding parameters depending on changes in the material elasticity ratio.

As applied to the present application, such material is the biological tissue of the larynx and the cord, whose elasticity ratio is suffering change under the impact of changes in glucose level in the human blood.

Therefore, it would be interesting to use the identified correlation between changes in the sound fluctuation spectrum of the voice of a person and changes in his/her blood biochemical parameters.

A non-invasive method is known of the determination of glucose concentration in blood based on the human voice, comprising the recoding of sound fluctuations of the voice of a person, instrumental transformation thereof for the purpose of obtaining a parameter correlated with the glucose content in the blood, and determination of the glucose content in the blood of the person at the time of such recording. Changes in the frequency of the sound fluctuation spectrum of the human voice were chosen as the parameter correlated with the glucose content in blood (www.fred.ucoz.ru^").

However, different people have different frequency characteristics of the larynx and cords, due to gender, age etc. In this regard, a method or device created on the basis of such methodology would have low precision of measurement and would be preferable only as an individual device. In the case of measuring glucose level in another patient with the same device, the error of measurement will be in the order of 40-50%.

Thus, low measurement precision may be said to be a major disadvantage of the state-of- the-art method.

It is also necessary to note that a change in blood glucose level entails not only a change of frequency, but also a change in the intensity of sound fluctuations. The main frequency area of the human speech is located in the range of from 100 Hz to 1 ,600-2,000 Hz, with the total intensity of sound fluctuations of this area being about 60 decibel. The difference between speech intensities of different people relative to each other is about 3-4 decibel.

Experiments dedicated to the measurement of peak intensities for selected frequencies in the human voice spectrum (measured with a sound spectrum analyzer) as related to the blood glucose level (measured by a standard glucometer) of different persons have shown that a certain influence of blood glucose level on the intensity of frequency peaks in the human voice spectrum is a reality.

Moreover, for the low-frequency area of the human speech, changes in peak intensities for the selected frequencies induced by changes in the blood glucose level amounted to 5-6 decibel, i.e. actually were in the same order as the differences of speech intensity of different people.

BRIEF SUMMARY OF THE INVENTION

Taking into consideration the above-said, the technical purpose of the invention is the creation of a device for the determination of biochemical properties of the blood, in particular blood glucose, by human voice.

In this invention, the set goal is achieved by creating a device for blood glucose concentration determination that comprises the line for glucose level measurement by human voice and the line for invasive blood glucose level measurement.

DETAILED DISCLOSURE OF THE INVENTION

In the claimed device, the line for measuring blood glucose level by human voice comprises consecutively installed microphone 1, sound recording module 2, analog-to-digital voice converter module 3, audio spectrum analyzer module 4, analog-to-digital voice spectrum converter module 5, spectrum frequency range selection module 6, selected frequency peak intensity determination module 7, selected frequency peak intensity ratios determination module 8, switch 9, spectrum peak intensity ratios to glucose level peak intensity ratios matching module 10, and glucose level display module 1 1.

The line for invasive blood glucose level measurement is connected, via switch 12, to selected frequency peak intensity ratios determination module 8, and comprises invasive glucometer module 13, analog-to-digital glucometer data converter module 14, peak intensity ratios database and glucose level database matching module 15, database averaging by glucose level module 16, and glucose level-averaged database and selected frequency peak intensity ratios matching module 17. Module 17 is connected, via switch 18, with spectrum peak intensity ratios to glucose level peak intensity ratios matching module 10.

The device is additionally equipped with module 20 for the determination of individual dependencies of changes in spectrum peak intensity ratios on glucose levels, which is connected via switch 19 with analog- to-digital glucometer data converter module 14.

The claimed device is shown schematically on the drawing.

According to fig.l , the line for measuring blood glucose level by human voice comprises consecutively installed microphone 1 , sound recording module 2, analog-to-digital voice converter module 3, audio spectrum analyzer module 4, analog-to-digital voice spectrum converter module 5, spectrum frequency range selection module 6, selected frequency peak intensity determination module 7, selected frequency peak intensity ratios determination module 8, switch 9, spectrum peak intensity ratios to glucose level peak intensity ratios matching module 10, and glucose level display module 11.

The line for invasive blood glucose level measurement is connected, via switch 12, to selected frequency peak intensity ratios determination module 8, and comprises invasive glucometer module 13, analog-to-digital glucometer data converter module 14, peak intensity ratios database and glucose level database matching module 15, database averaging by glucose level module 16, and glucose level-averaged database and selected frequency peak intensity ratios matching module 17. The latter is connected, via switch 18, with spectrum peak intensity ratios to glucose level peak intensity ratios matching module 10.

That line makes it possible to determine the generalized functional dependency of selected peak intensity changes in the spectrum on glucose levels with the help of a standard glucometer.

If necessary, to increase data precision by means of device adaptation to a specific individual and the determination of individual functional dependency of selected peak intensity changes in the spectrum on glucose levels, the schematic design additionally comprises module 20 for the determination of individual dependencies of changes in spectrum peak intensity ratios on glucose levels, which is connected via switch 19 with analog-to-digital glucometer data converter module 14, and via switch 21 - with spectrum peak intensity ratios to glucose level peak intensity ratios matching module 10.

The claimed device operates as follows:

Human voice is recorded with the help of microphone 1 in the selected low frequency range of 100 Hz to 1 ,500 Hz and high frequency range of 7,000 Hz to 10,000 Hz. The electric signal is received by sound recording module 2, wherefrom the audio recording is transmitted to analog-to-digital voice converter module 3 for voice digitization. The digitized human voice then goes to the input of audio spectrum analyzer module 4, wherefrom the obtained signal is transmitted to the input of analog-to-digital voice spectrum converter module 5. Then the signal is received at the input of spectrum frequency range selection module 6. The determination of peak intensities in the selected frequencies of the spectrum is performed in module 7: obtained peak intensity values are transmitted to the input of selected frequency peak intensity ratios determination module 8. Thereafter, the signal, on the one hand, may be transmitted via switch 9 to the input of spectrum peak intensity ratios to glucose level peak intensity ratios matching module 10 and glucose level display module 1 1, and on the other hand, via switch 12 - to the input of peak intensity ratios database and glucose level database matching module 15.

Initially, to determine the generalized functional dependency of selected peak intensity changes in the spectrum on glucose levels, standard invasive glucometer 13 is used, and, correspondingly, the line for invasive blood glucose level measurement. To obtain such dependency, glucose level values and corresponding voice changes of a multitude of individuals are recorded and matched. During that process, both the line for measuring blood glucose level by human voice and the line for invasive blood glucose level measurement are operating. From glucometer 13 the signal is transmitted to the input of analog-to-digital glucometer data converter module 14 for blood glucose level data digitization; that being performed, the digitized data are transmitted to the input of peak intensity ratios database and glucose level database matching module 15 and to database averaging by glucose level module 16, and then, consecutively, to the input of glucose level-averaged database and selected frequency peak intensity ratios matching module 17.

Thus, the functional dependency of glucose level changes on human voice spectrum changes in digital form is obtained, which is then used to measure blood glucose level in the blood of any individual. For that purpose, only the line for measuring blood glucose level by human voice shall be operative thereafter. The device may be used in that case as a common-use device. The data obtained by the authors demonstrate high measurement precision.

However, despite general regularities, there exist individual specifics of human voice changes depending on blood glucose level. To switch the device over to the individual use mode, module 20 for the determination of individual dependencies of changes in spectrum peak intensity ratios on glucose levels is used.

For that purpose, blood glucose concentration in the blood of an individual is measured with the help of invasive glucometer 13, and the signal is transmitted via analog-to-digital glucometer data converter module 14 and switch 19 to module 20. At the same time, information on the generalized functional dependency of selected peak intensity changes in the spectrum on glucose levels is received at the second input of module 20 from glucose level-averaged database and selected frequency peak intensity ratios matching module 17. As a result of matching of the data transmitted to module 20 from modules 14 and 17, an individual functional dependency of selected peak intensity changes in the spectrum on glucose levels is obtained. The signal is transmitted from module 20 via switch 21 to the input of spectrum peak intensity ratios to glucose level peak intensity ratios matching module 10 and glucose level display module 1 1. Thereafter, just as in the first case, only the line for measuring blood glucose level by human voice shall be operative, with the device used as an individual- use device. Thus, the proposed schematic design can be used in a variety of common- and individual-use devices, embedded in a telephone set or computer, or designed for the remote blood glucose level measurement in the blood of a person by his voice.

The claimed device was experimentally tried on five type 1 diabetics, two type 2 diabetics and three healthy individuals. For each trial subject, one day of testing was used for the calibration of the method. The other test days (from one to three for different individuals) were used for the restoration of glucose in the blood of the subjects. During test days, tests were conducted for half a day on an hourly basis, with changes in blood glucose concentration taking place in both directions (downward and upward). At the same time, for the sake of control, invasive measurements of blood glucose were conducted with the help of the Accu-Chek Active glucometer. Results of some of the experiments are shown in fig.2-4.

Fig.2 shows charts of human voice intensity changes depending on blood sugar levels for five insulin-dependent diabetics. The measurements were made with the help of Accu-Chek, a sound spectrum analyzer and a special calculation methodology developed for the determination of the functional dependency of the selected peak intensity on blood glucose level. Blood glucose levels are plotted on the ordinate, and relative dimensionless values of voice spectrum peak intensities are on the abscissa. Human voice recordings were made from mobile telephones with the simultaneous recording of blood glucose levels at the same instant of time. The trial was conducted for the period of one month. All subjects were diabetics since 5 to 10 years of a variety of ages from 40 to 75. The length of the trial was determined by the need to obtain blood sugar readings from maximum values to normal ones typical of the normal healthy individual.

Fig.3 shows test results of a bench version of the non-invasive device. Rhombus-like points on the chart correspond to blood glucose concentrations measured with the help of the invasive Accu-Chek glucometer. The line with square-like dots shows the results of the noninvasive bench device. Blood sugar levels are plotted on the ordinate, time (in hours) is plotted on the abscissa. Measurements were conducted on insulin-dependent diabetic M. by the two devices concurrently on an hourly basis beginning at 9am in the morning.

Fig.4 shows charts of measured blood glucose levels for another insulin-dependent diabetic subject.

Claims

WHAT IS CLAIMED IS:

1. A device for blood glucose level determination comprising a line for blood glucose level measurement by human voice and a line for invasive blood glucose level measurement.

2. The device according to claim 1. wherein the said line for blood glucose level measurement by human voice comprises consecutively installed microphone, sound recording module, analog-to-digital voice converter module, audio spectrum analyzer module, analog-to- digital voice spectrum converter module, spectrum frequency range selection module, selected frequency peak intensity determination module, selected frequency peak intensity ratios determination module, switch, spectrum peak intensity ratios to glucose level peak intensity ratios matching module, and glucose level display module.

3. The device according to claim 1 , wherein the said line of invasive blood glucose level measurement is connected, via a switch, to the said selected frequency peak intensity ratios determination module, and comprises an invasive glucometer module, analog-to-digital glucometer data converter module, peak intensity ratios database and glucose level database matching module, a module for database averaging by glucose level, and a glucose level- averaged database and selected frequency peak intensity ratios matching module.

4. The device according to claim 1, wherein it additionally comprises a module for the determination of individual dependencies of changes in spectrum peak intensity ratios on glucose levels, which is connected via a switch with the said analog-to-digital glucometer data converter module.