RU2506893C1 - Method of non-invasive determination of glucose in blood and device for its realisation - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, endocrinology and can be used for determination and control of level of glucose in blood in the process of diagnostics of carbohydrate metabolism disorders. Sound fluctuations of person's voice are registered, their instrument conversion is performed to obtain parameter, corresponding to content of glucose in blood, and content of glucose in person/s blood is determined in the process of registration of sound fluctuations. Intensity of peaks of audio frequencies of person's voice fluctuations is used as parameter, corresponding to content of glucose in blood. Ratio between intensities of peaks of selected low and high frequencies is used as said parameter of intensity. Registration of sound fluctuations of person's voice is performed in selected range of low frequencies from 100 Hz to 1500 Hz and high frequencies from 7000 Hz to 10000 Hz. Device for determination of level of glucose in person's blood includes register of sound fluctuations of person's voice, audio spectrum analyser with filters for selection of peaks of spectrum in the area of low and high frequencies, unit for processing data from spectrum-analyser and unit for determination of the value of glucose level depending on change of intensity of selected spectrum peaks.

EFFECT: group of inventions ensures non-invasive accurate and simple enough determination and constant control of glucose level in person's blood.

9 cl, 4 dwg, 1 ex

Description

The invention relates to medicine, in particular to endocrinology, and can be used to control blood glucose levels in the diagnosis of carbohydrate metabolism disorders, for differential diagnosis of insulin-dependent and non-insulin-dependent diabetes, determining the state of their compensation.

Diabetes mellitus is a chronic disease that occurs as a result of insufficient insulin production by the pancreas or ineffective susceptibility of insulin produced by the body's cells.

Diabetes mellitus is a very common disease; the number of people affected by this disease is growing year by year. Already today, diabetes affects more than 60 million people on earth.

Diabetes requires constant monitoring of blood glucose, otherwise the disease can lead to serious complications. Only when maintaining the concentration of glucose in the blood within the normal range (3.5-6.0 mmol / L) is it possible to stop the development of complications. Proper diet and physical activity, maintaining a normal or near normal level of glucose in the blood will prevent the development of diabetic complications.

Blood tests for sugar are widespread, in which it is necessary to obtain a blood sample in the form of a drop. To do this, use special automatic devices for piercing the skin. Determination of sugar level is carried out in the laboratory. Known methods for analyzing a patient’s blood sugar are based on the property of sugar to restore certain salts during complex chemical reactions; such analyzes are biochemical in nature.

Blood for testing for glucose in it is taken in various ways - from a vein, by piercing the skin of your fingertips, earlobe. In the first case, venous blood is examined, in the second - capillary blood. Currently, portable devices for determining blood sugar have been created, which patients at home can use and themselves can determine the level of sugar. This is necessary for the correct selection of doses of drugs for patients with diabetes, which significantly increases the effectiveness of treatment.

The disadvantage of such methods is that they are expensive and, most importantly, require mandatory blood sampling. In this case, injury and infection of a person is possible.

Known non-invasive methods for determining glucose in human blood, excluding blood sampling.

For example, there is a known method for determining the concentration of glucose in human blood based on measuring the total electrical resistance of the skin or one of the components of the total electrical resistance of the skin (RU 2230485, 2004).

However, this method has low sensitivity to determining glucose concentration, as it uses a calculation formula that includes difficult to determine parameters. Such parameters, although they take into account the relationship of glucose concentration with the electrical parameters of the skin, but depend on the ionic composition of the fluids and perspiration, which vary greatly in different people.

A known method for determining the concentration of glucose in human blood and continuous monitoring of the state of glucose concentration in human blood (RU 2342071, 2007). The method consists in measuring electric transfer functions by means of two pairs of four-electrode sensors fixed to the surface of a human body.

The disadvantage of this method is the low sensitivity to determine the concentration of glucose, because glucose is electrically neutral. Its concentration in the blood is three orders of magnitude lower than the concentration of electrolytes in the blood and in biological tissues.

Known non-invasive method for determining the concentration of glucose in human blood (RU 2295915, 2005). The method is carried out by irradiating with a laser beam the zone of maximum congestion of blood vessels on the mucous membrane, receiving information and instructing it by highlighting the orientation of the polarization vector and the intensity of the reflected radiation and calculating the concentration of the substance in the blood from them. For irradiation using a laser beam with "zero polarization" and a wavelength in the range of 0.5 microns - 2.1 microns. The polaroid analyzer is preliminarily tuned to the points of local absorption of laser radiation in the mucous tissue of the substances being determined, the changes in the orientation of the polarization vector of the reflected radiation at the points of local absorption of laser radiation are recorded by the angle of rotation and the substance concentration is determined by the angle of rotation of the polarization vector.

However, this method has low accuracy, since the blood vessels, for example, in the dermis are at a depth of the order of a millimeter from the stratum corneum. In addition, the surface layers of the skin are anisotropic, and the propagation of linearly polarized light leads to an ambiguous interpretation of the measurement results.

A non-invasive method for determining glucose concentration is known, including measuring systolic and diastolic blood pressure sequentially on the patient's left and right hands, while the blood glucose is calculated by mathematical formulas (RU 2368303, 2007).

However, this method is complicated and not accurate enough, since it requires measuring the pressure on the patient’s right and left hands on an empty stomach and after eating, and the blood glucose is calculated according to the mathematical formulas proposed by the applicant.

Scientists from Israel and the United States have developed a method for the early diagnosis of Parkinsonism, based on an assessment of the subtlest changes. human voices, reports The Daily Telegraph. Currently, parkinsonism is diagnosed, as a rule, only when the death rate of motor neurons is large enough to cause symptoms such as muscle stiffness, tremors and imbalances.

Treatment initiated at this stage may slow the progression of the disease, but not restore motor function. Timely diagnosis, according to the researchers, can prevent the destruction of up to 60 percent of nerve cells in the corresponding areas of the brain. It is also known that parkinsonism disrupts the function of the muscles of the larynx, which sooner or later leads to hoarseness.

Based on this fact, attempts at early diagnosis of the disease by voice changes have already been carried out, but have been unsuccessful. A professor at the University of Haifa, Shimon Sapir, was able to do this by taking an alternative approach to voice analysis and developing software that identifies his characteristic changes due to illness before they become audible.

It should be noted that the voice itself, regardless of what words are pronounced, carries an enormous amount of information; the voice can determine the character of a person and much more.

This is explained by the fact that the voice is directly related to anatomy and physiology: it depends on the structure of the body in general and the organs of voice formation in particular. Sounds are produced by vibrations of the vocal folds, which, like strings, are stretched in the larynx. They can perform from 80 to 10,000 or more oscillations per second, and fluctuate with their entire mass, as well as individual sections. It has been established that under the influence of nerve impulses coming from the central nervous system, the vocal folds change their length, thickness, and degree of tension. The reduction of their various sections determines the whole rich gamut of sounds, just as pressing fingers on guitar strings in different places gives a different sound.

The pitch of the voice depends on the length of the folds, and their length and thickness depends on the structure of the larynx. The timbre of the voice, its strength, color depends not only on the length and thickness of the folds, but also on the structure of the so-called resonators.

The pharynx, nasopharynx, mouth, nasal cavity and sinuses are the upper resonators, and the trachea, bronchi and lungs are the lower ones. Each person has these individual characteristics, so the voices are so dissimilar.

As already noted, the voice is associated with anatomy and physiology, so almost any disease, one way or another, affects the sound of the voice. The voice changes with various bronchitis, tonsillitis, sinusitis ...

Sophisticated electro-acoustic processing of a voice uttering phrases expressing different emotions - joy, grief, anger, fear, showed that each state of a person has its own set of distinctive acoustic features. For example, for the state of grief - this is the longest syllable, the characteristic “rises” and “congresses” in the height of the sounds, for fear - the sharp changes in the strength of the voice, violation of the tempo, pauses ...

So, the voice accurately informs others about the current state of a person. These reactions are usually poorly controlled by the person himself, and therefore they are very informative.

When a person’s emotional state changes, a large number of speech characteristics change uncontrollably. These primarily include: a change in the frequency of the fundamental tone and the first few formants, changes in the spectral composition of speech, an increase in the energy of high-frequency components, an increase in the volume and pace of speech, the appearance of vibration; other changes also occur that can be described in mathematical form and, therefore, calculated using a computer. Thus, the detection of a wide range of characteristics listed above can, with a high degree of certainty, reveal changes in the psychoemotional state of a person.

Currently, there are known methods for determining the psychophysiological state of a person based on the connection of ongoing mental processes with the dynamics of physiological processes, which is used, for example, in "lie detectors".

In this case, the parameters of the human condition can be recorded using external devices that are not directly connected to the person.

However, the parameters of the sound vibrations of a person’s voice can change not only when the emotional state changes, but also due to physiological changes in the larynx and vocal cords when various biochemical characteristics of the human blood change, for example, when the blood glucose level changes.

Studies have shown that with a change in the level of glucose in the blood, including one that washes the larynx and ligaments, the elastic properties of the biological tissue of these organs will change, which accordingly will also lead to a change in the spectral characteristics of sound vibrations in the human voice (which corresponds to the physical Hooke's law).

Thus, a theoretical analysis of the vibration spectrum of a two-dimensional plate shows that as a result of a change in the coefficient of elasticity of the plate material, the spectral composition of the plate vibrations also changes. New overtones appear, a frequency shift of the peaks and a change in the intensity of some peaks in the spectrum of vibrations occur. All these changes in the spectrum can be used as quantitative values of the change in the corresponding parameters depending on the change in the coefficient of elasticity of the material.

In relation to this application, such material is the biological tissue of the larynx and ligaments, the coefficient of elasticity of which undergoes a change under the influence of changes in the level of glucose in human blood.

Thus, it would be interesting to take advantage of the revealed dependence of changes in the spectrum of sound vibrations of a person’s voice on changes in glucose levels in his blood. This dependence could be the basis for creating a method for non-invasive determination of glucose in the blood of humans and animals.

A non-invasive method is known for determining the concentration of glucose in the blood from a person’s voice, including recording the sound vibrations of a person’s voice, transforming them in hardware to obtain a parameter corresponding to the blood glucose, and determining the glucose level in a person’s blood when recording sound vibrations. In this case, as a parameter corresponding to the content of glucose in the blood, a change in the frequency of the spectrum of the sound vibrations of a person’s voice is selected.

However, the frequency characteristics of the ligaments and larynx are different for all people, which is associated with gender, age, etc. In this regard, a method or device created on the basis of such a method has low measurement accuracy and is preferred only as an individual. When measuring the glucose level of another person using such a device, the measurement error will be about 40-50%.

Thus, the main disadvantages of this method include the low accuracy of the measurement.

It should also be noted that a change in the level of glucose in the blood entails not only a change in frequency, but also a change in the intensity of sound vibrations.

In this case, the main area of human colloquial speech in frequency ranges from 100 Hz to 1600-2000 Hz, and the total intensity of sound vibrations in this area is about 60 decibels. The change in the intensity of colloquial speech of different people relative to each other is about 3-4 decibels.

Experiments to measure the intensity of peaks for selected frequencies in the spectrum of a person’s voice (measured using a sound spectrum analyzer) as a function of blood glucose (measurements were carried out with a standard glucometer) for different people showed that the effect of blood glucose on the change in the intensity of frequency peaks in the spectrum human voices really exist.

Moreover, for the low-frequency region of colloquial speech, the change in the peak intensity for the selected frequencies under the influence of a change in blood glucose is about 5-6 decibels, i.e. almost at the level of change in the intensity of colloquial speech of different people.

Thus, the technical task of the invention is the creation of a non-invasive method for measuring glucose in human blood, allowing with sufficient simplicity and accuracy to continuously monitor the level of glucose in human blood, and a device for its implementation.

The technical result of the invention is to increase the accuracy of measurements due to the choice as a parameter corresponding to the content of glucose in the blood, the intensity of the peaks of the sound frequencies of the vibrations of a person’s voice.

To solve this problem, in the known method of non-invasive determination of glucose in the blood from a person’s voice, including recording the sound vibrations of a person’s voice, their hardware conversion to obtain a parameter corresponding to the glucose content in the blood, and determining the glucose content in a person’s blood when recording sound vibrations, in as a parameter corresponding to the content of glucose in the blood, choose the intensity of the peaks of the sound frequencies of the oscillations of the human voice.

In this case, the hardware conversion includes the conversion of the sound vibrations of a person’s voice into a spectrum, the selection of spectral peaks of sound frequencies with a uniform intensity in the low and high frequencies, the determination of the intensities of the selected peaks in frequency and obtaining the ratio between the intensities of the peaks of the selected low and high frequencies.

In addition, the functional dependence of the change in the ratio of intensities of the selected peaks depending on the glucose level in the blood is preliminarily determined using a standard glucometer.

In this case, the functional dependence of the change in the ratio of the selected peaks on the blood glucose level can be a generalized average functional dependence obtained by recording the sound vibrations of voices of different people or an individual functional dependence obtained by recording the sound vibrations of one person’s voice.

Preferably, the registration of the sound vibrations of the human voice is carried out in a selected range of low frequencies from 100 Hz to 1500 Hz and high frequencies from 7000 Hz to 10000 Hz.

Also proposed is a device for implementing the method according to claim 1, comprising a recorder of sound vibrations of a human voice, a sound spectrum analyzer with filters for selecting spectrum peaks in the low and high frequencies, a data processing unit from a spectrum analyzer, and a unit for determining the value of glucose depending from changes in the intensity of the selected peaks of the spectrum.

It is preferable that a microphone is used as a recorder of sound vibrations of a person’s voice, and a computer is used as a data processing unit from a spectrum analyzer and a unit for determining the value of glucose depending on changes in the intensity of the selected spectrum peaks.

The method is implemented as follows: a person whose blood glucose level they want to measure, pronounces a standard phrase into a microphone, for example, a voice recorder, telephone or computer, in which there is a sound spectrum analyzer program. Then, using the data processing unit from the spectrum analyzer and the unit for determining the level of glucose depending on the change in the intensity of the selected peaks of the spectrum, the sound vibrations of the human voice are converted into the spectrum, spectral peaks of sound frequencies with uniform intensity in the low and high frequencies are selected, determine the intensity of the selected peaks in frequency, get the ratio between the intensities of the peaks of the selected low and high frequencies, and determine the level of glucose in the blood from them.

The functional dependence of the change in the ratio of intensities of the selected peaks depending on the glucose level in the blood is preliminarily determined using a standard glucometer and a generalized average statistical functional dependence obtained by recording sound vibrations of voices of different people or an individual functional dependence obtained by recording sound vibrations of one person’s voice is obtained.

An appropriate technique was developed to obtain a database of measurements for many people, mainly patients with insulin-dependent diabetes. For each person, at least 10 values of glucose were measured, and at the same time, sound recording of a person's voice was made. A computer with a microphone and a sound spectrum analyzer program were used as a bench device for processing incoming data and sugar levels. Using a spectrum analyzer, the sound recording of a human voice was converted into a spectrum both in the form of digital data and in the form of a spectral graph. Spectral graphs were graphs of both individual peaks and solid, merging peaks with different intensities. According to the ordinate of the graph - the magnitude of the intensities of the peaks, along the abscissa - the frequency of sound vibrations. Initially, the obtained databases were analyzed by the visual method, in which qualitative changes were considered on the graph of the sound spectrum of the voice depending on the level of glucose. In accordance with this method of analyzing the spectrum graphs and the corresponding values of the glucose level, frequency ranges were found in which the peak intensities strongly varied depending on the change in glucose value for each person individually. Then, such regular changes in the peak intensity in these frequency ranges were found for all people participating in the experiment with a change in glucose level. After that, to increase the accuracy of measurements, relative intensities such as harmonic relations were used.

To obtain quantitative functional dependences of the change in peak intensities on the values of glucose levels, we used digital databases of the sound spectrum of each person’s voice.

A device for measuring the level of glucose in the blood according to the person’s voice is shown schematically in the drawing (Fig. 1) and includes a microphone 1, a sound spectrum analyzer with filters for selecting peaks of spectrum 2, in which the person’s voice decomposes into a spectrum, a computer with blocks 3, in which there is a program for processing incoming data, a processor unit 4, with which the glucose level is determined, and a telemetry unit 5, with which the result of measuring blood glucose is shown.

The device operates as follows. From microphone 1, the audio recording enters the block of the sound spectrum analyzer 2, where the conversion of the human voice into the spectrum is performed. In digitalized form, the data is transmitted to the computer and to the telemetry unit 5, where the result of measuring the glucose level is visible.

Examples of the method.

The inventive method was tested experimentally on five first-type diabetics, two second-type diabetics and three healthy people. Moreover, one test day for each subject was used to calibrate the method. The remaining test days (from one to three for different subjects) were used to restore glucose in the blood of the subjects. Tests on test days were carried out for half a day every hour, while changes in blood glucose occurred in different directions (in the direction of decreasing and increasing it). At the same time, invasive measurements of blood glucose were performed using Accu-Chek Active instruments for control. The results of some of these experiments are shown in FIGS. 2-4.

Figure 2 shows graphs of changes in the intensity of a person's voice depending on the level of sugar for five people of insulin-dependent diabetics. The measurements were carried out using the AkUchek instrument, a sound spectrum analyzer, and a developed calculation procedure for determining the functional dependence of the intensity of selected peaks on glucose level. The ordinate shows glucose levels. The abscissa shows the relative dimensionless values of the intensity of the peaks of the voice spectrum. Recordings of human voices were made from cell phones with the simultaneous reporting of the glucose level at a given time. Tests were carried out for a month. All subjects are diabetics with an experience of 5 to 10 years and different ages from 40 to 75 years. The duration of the tests was determined by the need to obtain the value of the sugar level from maximum values to normal values corresponding to a healthy person.

Figure 3 presents the test results of a bench sample of a non-invasive device. Dots in the form of rhombs on the graph correspond to the values of glucose concentration in the blood, measured with the help of the invasive device AkUchek. A line with dots in the form of squares shows the results of a non-invasive bench device. The ordinate shows the sugar level. The abscissa is the time in hours. The measurements were carried out on an insulin-dependent diabetic M. simultaneously with two devices every hour. Measurements began at 9:00 a.m.

Figure 4 presents graphs of the measured values of glucose levels for the second test insulin-dependent diabetic.

Claims (9)

1. The method of non-invasive determination of glucose in the blood from a person’s voice, including recording the sound vibrations of a person’s voice, their hardware conversion to obtain a parameter corresponding to the glucose in the blood, and determining the glucose content in a person’s blood when recording sound vibrations, characterized in that as a parameter corresponding to the content of glucose in the blood, choose the intensity of the peaks of the sound frequencies of the oscillations of the human voice. 2. The method according to claim 1, characterized in that the ratio between the intensities of the peaks of the selected low and high frequencies is used as an intensity parameter. 3. The method according to claim 1, characterized in that the apparatus conversion includes converting the sound vibrations of a person’s voice into a spectrum, selecting spectral peaks of sound frequencies with uniform intensity in the low and high frequencies, determining the intensities of the selected peaks in frequency and obtaining the relationship between peak intensities of selected low and high frequencies. 4. The method according to claim 3, characterized in that the functional dependence of the change in the ratio of intensities of the selected peaks depending on the level of glucose in the blood is preliminarily determined using a standard glucometer. 5. The method according to claim 4, characterized in that the functional dependence of the change in the ratio of selected peaks on the level of glucose in the blood is a generalized average functional dependence obtained by recording the sound vibrations of voices of different people. 6. The method according to claim 4, characterized in that the functional dependence of the change in the ratio of selected peaks on the level of glucose in the blood is an individual functional dependence obtained by recording the sound vibrations of one person’s voice. 7. The method according to claim 1, characterized in that the registration of the sound vibrations of a person’s voice is carried out in a selected range of low frequencies from 100 Hz to 1500 Hz and high frequencies from 7000 Hz to 10000 Hz. 8. The device for implementing the method according to claim 1, comprising a recorder of sound vibrations of a human voice, a sound spectrum analyzer with filters for selecting spectrum peaks in the low and high frequencies, a data processing unit from a spectrum analyzer and a unit for determining the value of glucose depending from changes in the intensity of the selected peaks of the spectrum. 9. The device according to claim 8, characterized in that a microphone is used as a recorder of sound vibrations of a person’s voice, and a computer is used as a data processing unit from a spectrum analyzer and a unit for determining the value of glucose depending on changes in the intensity of the selected spectrum peaks.

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