RU2559640C1 - Diagnostic technique for microangiopathy in diabetic patients - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: rest capillaroscopy is followed by measuring changes in the capillary state structure. That is accompanied by acapillaroscopy and oxygenometry with four provocative tests involving the examined limb exposure to physical factors, including a cuff occlusion, a cold test, a thermal test, and a test with arms lifted up. Each test is followed by measuring an oxygen saturation index (SaO) and a capillaroscopy values reset time (t). After the cuff occlusion SaOand tare supposed to be measured. The cold test is followed by measuring SaOand t. The thermal test - by measuring SaOand t. SaOand tappear after the test with arms lifted up has been completed. If SaO- 85-90%, t<20 seconds, SaO>95%, t<5 minutes, SaO>95%, t<4 minutes 30 seconds, SaO- 85-90%, t<15 seconds, early microangiopathy is diagnosed. If SaO- 80-85%, t- 20-30 seconds, SaO- 87-95%, t- 5 minutes - 6 minutes 30 seconds; SaO- 90-95%, t<4 minutes 30 seconds - 5 minutes, SaO- 78-85%, t- 15-25 seconds, moderate microangiopathy is diagnosed. SaO<80%, t>30 seconds; SaO<87%, t>6 minutes 30 seconds; SaO<90%, t>5 min; SaO<78%, t> 25 seconds show pronounced microangiopathy.EFFECT: method provides diagnosing microangiopathy as accurately as possible in the given category of patients by the early integrated microvasculature assessment associated with detecting the capillary reserve level.2 tbl, 2 ex

Description

The invention relates to medicine, namely to endocrinology, and can be used to diagnose the early stages of microangiopathy in patients with diabetes mellitus (DM).

Today, the use of effective treatment for patients with diabetes in most cases can prevent the development of acute complications and significantly reduce their frequency. At the same time, the problem of early diagnosis of the complications of the disease remains urgent: angiopathies, neuropathies, etc., the number of which increases with the experience of the disease. In the first months of the onset of hyperglycemia, aldose reductase, non-enzymatic protein glycation, free radical oxidation, etc. are activated. These metabolic changes lead to damage to the vascular wall already in the onset of the disease, but in the initial stages a reversible character is possible. In this regard, it is necessary to develop new, more effective methods for the diagnosis of diabetic microangiopathy, allowing to identify the earliest changes in microcirculation, mainly of a functional nature.

A known method for the diagnosis of microangiopathy in patients with diabetes mellitus (Method for determining the reactivity of blood vessels // Lukyanov V.F., Lukyanova S.V. RF patent for invention No. 2018263, publ. 30.08.1994), which includes irradiating a fixed part of the body with monochromatic visible light and determining the amount of reflected light before and during a functional test with compression of the limb, and then evaluating the results obtained by the ratio of the intensity of the reflected light to the original value.

The disadvantages of this method are the lack of visualization of capillaries and the assessment of their structural disturbances, the inability to determine the compensatory capabilities of capillaries, the state of the reserve microcirculation system and the severity of peripheral tissue hypoxia.

There is also a method for the diagnosis of microangiopathy in patients with diabetes mellitus (1. A method for the early diagnosis of microangiopathy in patients with type 1 diabetes mellitus // Kasatkina SG, Panova TN Patent of the Russian Federation for the invention No. 2316004, publ. January 27, 2008) , which consists in the study of venous blood, when the content of methemoglobin and sulfhemoglobin is determined in the patient’s blood at the same time, the transformation coefficient of methemoglobin into sulfhemoglobin is calculated.

The disadvantages of this method are the invasiveness of the study, the need for direct contact with the blood of the subjects, the availability of special equipment for recording biochemical parameters, the presence of qualified personnel, the absence of a comprehensive morphofunctional assessment of microcirculation and the inability to assess the level of compensatory capillary capabilities.

As a prototype of the proposed method, a method for diagnosing microangiopathy in patients with diabetes mellitus (1. Kaminska-Winciorek G. Diabetic microangiopathy in capillaroscopic examination of juveniles with diabetes type 1 / G. Kaminska-Winciorek, G. Deja, J. Polańska [et al. ] // Postepy Hig Med Dosw. - 2012. - No. 66. - P. 51-59), which consists in studying the capillaries of the nail bed of the ring fingers of the patient’s hands at rest, assessing their structural changes by determining the main capillaroscopic parameters using a computer capillaroscope with photographing function.

The prototype and the claimed invention has the following essential features: conducting capillaroscopy at rest and subsequent assessment of structural changes in the state of capillaries.

The disadvantage of this method is that the known method does not fully realize the capabilities of the diagnostic algorithm, which limits its use in the initial stages of microangiopathy in patients with diabetes mellitus.

At the same time, the doctor is not able to identify pathological changes in the capillaries in patients in the onset of diabetes mellitus and with an insignificant duration of the disease, which does not allow to assess the state of the reserve microcirculation system and the severity of peripheral tissue hypoxia, establish the stage of microangiopathy, and ultimately monitor the condition of the capillaries in the patient with diabetes in dynamics.

The objective of the invention is to improve the diagnostic algorithm of microangiopathy in patients with diabetes mellitus, which allows to comprehensively assess the state of the microvasculature in the early stages of the disease and establish the level of reserve capacity of capillaries, which can facilitate timely treatment and prevention of vascular complications.

A new technical result achieved by the invention is to increase the accuracy and informativeness of the diagnosis of microangiopathy in patients with diabetes, which will allow you to choose the most effective therapeutic tactics individually for each patient.

This technical result is achieved by the fact that in a method for diagnosing microangiopathy in patients with diabetes mellitus, including conducting capillaroscopy at rest followed by an assessment of the structural changes in the state of the capillaries, they additionally carry out capillaroscopy and oxygenometry with four functional tests with the influence of physical factors on the limb under study - cuff occlusion, test with a cold effect, a sample with a thermal effect, a sample with a limb raised up, and after each of the samples, determine SaCO ₂ oxygenation indicator and recovery time of capillaroscopy indices t to initial values, after occlusion - SaCO _{2 okl.} and t _approx. , after cold exposure - SaO _{2 cold.} and t _cold. after heat exposure - SaO _2tepl. and t is _warm. , after raising the limb up - SaO _{2 up} and t _up and diagnose the initial stage of microangiopathy with SaO _{2 okl.} - 85-90%, t _approx. <20 sec, SaO _{2 hall.} > 95%, t _cold. <5 min, SaO ₂ heat _. > 95%, t _heat. <4 min 30 sec, SaO _{2 up} - 85-90%, t _Вepx. <15 sec, a moderate stage of microangiopathy is diagnosed with SaO _{2 okl.} - 80-85%, t _approx. - 20-30 sec; SaO _{2 hall.} - 87-95%, t _cold. - 5 min - 6 min 30 sec; SaO _{2 warm} - 90-95%, t _heat. - 4 minutes 30 seconds - 5 minutes; SaO _{2 up} - 78-85%, t _upx. - 15-25 seconds, diagnose a pronounced stage of microangiopathy with SaO _{2 okl.} <80%, t _approx. > 30 sec; SaO _{2 cold} <87%, t _cold. > 6 min 30 sec; SaO _{2 warm} <90%, t _heat > 5 min; SaO _{2 up} <78%, t _upx > 25 sec.

The method is as follows.

A patient with a diagnosis of type 1 diabetes is subjected to a standard comprehensive examination, which includes determining the level of glycated hemoglobin, microalbuminuria, ultrasound examination of the kidneys, examination of the fundus and consultation of a neurologist.

Then the patient is carried out oxygenometry at rest.

For this patient, after 15-20 minutes of rest in a sitting position at an ambient temperature of 18-21 ° C, they are asked to lay the test arm horizontally on the table, slightly bending it in the elbow joint. A pulse oximeter, for example, an Onyx 9500 finger pulse oximeter manufactured by Nonin, is applied to the little finger of the test arm. Determine the oxygenation rate of capillary blood SaO ₂ , which is normally 95-100%.

Next, the patient undergo capillaroscopy at rest. To do this, immersion oil (refractive index, n _d = 1.515 ± 0.002) is applied to the nail roller of the ring finger of the hand of the test hand, and capillaroscopy is performed using a capillaroscope, for example, a CAM-04 digital microscope capillaroscope manufactured by Sigeta. Using capillary morphometry software such as Digi-microscope v. 1.1, determine the following parameters: the length of the capillary loops (l _cap. ) In microns, the diameter of the arterial sections of the capillaries (d _art. ) In microns, the transitional sections of the capillaries (d _per. ) In microns, the venous sections of the capillaries (d _ven. ) In microns ; determine the ratio of the diameters of the arterial sections of the capillaries to the venous (d _art. / d _ven. ).

Conduct a test with an occlusion cuff.

To do this, put a cuff on the shoulder of the arm under study at a distance of 2-3 cm from the elbow, inject air into the cuff to values that exceed the level of disappearance of Korotkov tones by 20-30 mm RT. Art. After 40-45 seconds, the oxygenation index of capillary blood after occlusion of SaO _{2occl is determined.} using a pulse oximeter superimposed on the little finger of the examined hand. A capillaroscopy of the nail roller of the ring finger is carried out, where immersion oil was applied, recording changes in capillaroscopic parameters. Gently release air from the cuff and set the recovery time of capillaroscopic indices to the initial values after occlusion t _approx. . At the end of the test, the cuff and pulse oximeter are removed from the patient’s examined hand.

Then conduct a test with cold exposure.

This test is carried out by placing the brush of the patient’s examined hand for 4-6 minutes in a container with water, the temperature of which is 5-7 ° C. At the end of this time, the hand is removed from the container, dried with a paper towel. Next, a pulse oximeter is applied to the little finger of the test arm and the capillary blood oxygenation index is determined after cold exposure to SaO _2chol. . Immersion oil is applied to the nail roller of the ring finger, and capillaroscopic indices are evaluated using a capillaroscope. Then record the time of restoration of capillaroscopic indicators to the original values after cold exposure t _cold. . At the end of the cold exposure test, the patient is taken out of the pulse oximeter from the little finger of the examined hand and the remaining immersion oil on the nail roll of the ring finger is removed with a napkin.

Then conduct a test with thermal exposure.

For a sample with thermal effect, the hand of the studied hand is immersed for 4-6 minutes in a container of water, whose temperature is 42-46 ° C. After this time, the hand is removed from the container, dried with a paper towel. Then apply a pulse oximeter on the little finger of the test arm and determine the oxygenation index of capillary blood after heat exposure to _SaO2tepl. . Immersion oil is applied to the nail roller of the ring finger, a capillaroscopic examination is performed using a capillaroscope. Then, the recovery time of capillaroscopic indices to the initial values after thermal exposure t heat is recorded _. . The patient is removed the pulse oximeter from the little finger of the examined hand and the remnants of immersion oil on the nail roller of the ring finger are removed with a napkin.

Then carry out a test with raising the limb up.

A pulse oximeter is placed on the little finger of the examined hand. Next, the hand is raised for 2-2.5 minutes vertically up. At their end, the hand is quickly lowered to its original position, the oxygenation index of capillary blood is recorded after raising the limb up SaO _{2 up} . Next, immersion oil is applied to the nail roller of the ring finger and capillaroscopy is performed. The changes in capillaroscopy indices are recorded after the arm is raised vertically, and then the recovery time of the capillaroscopic indices is set to the initial values after the limb is raised up t _up . At the end of the test, the pulse oximeter is removed and the immersion oil is removed with a napkin from the nail roller of the ring finger.

Diagnose the initial stage of microangiopathy in patients with diabetes with the following values: SaO _{2 okl.} - 85-90%, t _approx. <20 sec, SaO _{2 hall.} > 95%, t _cold. <5 min; SaO _{2 warm} > 95%, t _heat. <4 min 30 sec, SaO _{2 up} - 85-90%, t _up <15 sec.

A moderate stage of microangiopathy is diagnosed with the following indicators: SaO _{2 okl.} - 80-85%, t _approx. - 20-30 sec; SaO _2hol. - 87-95%, t _cold. - 5 min - 6 min 30 sec; SaO _{2 warm} - 90-95%, t _heat. - 4 minutes 30 seconds - 5 minutes; SaO _{2 upx} - 78-85%, t _up - 15-25 sec.

The expressed stage of microangiopathy is established at the following values: SaO _{2 okl.} <80%, t _approx. > 30 sec; SaO _{2 hall.} <87%, t _cold. > 6 min 30 sec; SaO _{2 warm} <90%, t _heat > 5 min; SaO _{2 up} <78%, t _up > 25 sec.

The proposed method was tested on 78 subjects: men - 33, women - 45; the average age is 24 ± 2.7 years. The subjects were divided into two groups: group I — control, consisting of 20 practically healthy people, of which 10 were men, 10 were women, and the average age was 21 ± 2.3 years; II group - 58 patients with type 1 diabetes mellitus, 23 of them men, 35 women; the average age is 25 ± 2.9 years. The average duration of diabetes mellitus was 4.2 ± 0.6 years.

The statistical significance of the differences between the 1st and 2nd groups was determined using the Mann-Whitney criterion (U-test) and estimation of the value of the p-level of significance.

The data obtained during functional tests on the severity of microangiopathy in patients with diabetes mellitus were confirmed by the results of clinical and laboratory studies, including determining the level of glycated hemoglobin, microalbuminuria, ultrasound examination of the kidneys, examination of the fundus and consultation of a neurologist.

Table 1 shows the indicators of capillaroscopy of the upper extremities during diagnostics by the prototype method and by the claimed method.

As can be seen from table 1, when conducting diagnostics by the prototype method, a decrease in d _{art was} found in patients of group II in comparison with group I. (p = 0.047) and a decrease in d _art. / d _van. (p = 0.035).

The inventive method in addition to the above changes additionally revealed in patients of the II group in comparison with the I-th increase in d _veins. (p = 0.022) during the test with cuff occlusion. A sample with cold exposure revealed a decrease in l _cap. (p = 0,031), a pronounced decrease in d _art. (p = 0.018) and d _veins. (p = 0.038), decrease in d _art. / d _veins (p = 0.031).

When tested with thermal exposure, a decrease in l _cap. (p = 0.043), the absence of caused dilation d _art. (p = 0.033), d _veins. (p = 0.047) and, accordingly, insufficient increase in d _art. / d _veins (p = 0.020).

The test with raising the limb up revealed a sharp decrease in l _cap in patients of group II in comparison with group I. (p = 0.019), narrowing d _apt. (p = 0.033), d _per. (p = 0.028) and d _veins. (p = 0.036), decrease in d _art. / d _veins (p = 0.044).

The above indicators confirm that the inventive method for the diagnosis of microangiopathy in patients with diabetes has a greater sensitivity and informativeness compared to the prototype method.

Table 2 shows the functional indicators obtained during the diagnosis according to the claimed method.

As can be seen from table 2, SaO ₂ at rest was within normal limits and, accordingly, amounted to 98% in both the I and II groups.

When performing functional tests, a number of changes in capillaroscopy indices were found in patients of group II in comparison with group I.

When conducting a test with an occlusion cuff in patients in group II, the SaO indicator is _2occl. statistically significantly decreased in comparison with the 1st (p = 0,0008), and t _okl. - lengthened (p = 0.012).

When conducting a functional test with a cold effect, a decrease in SaO _2chol was observed in the group II _studied. (p = 0.002) and t _cold. elongation in comparison with group I (p = 0.026).

When conducting a functional test with thermal effect in the II group revealed a decrease in SaO _2tepl. (p = 0.04) and elongation t _heat. (p = 0.038).

Conducting a test with raising the limb up caused a decrease in blood supply and, consequently, a decrease in SaO _{2 up} . In the II group, SaO _{2 up} was less important than in the I group (p = 0.004). An elongation of t _{up was} revealed (p = 0.02).

A method for the diagnosis of microangiopathy in patients with diabetes is illustrated by the following examples.

Example 1

Patient A., 21 years old, with a diagnosis of type I diabetes, severe, subcompensation phase. Diabetic distal polyneuropathy, sensory form. " On admission, she complained of thirst, polyuria, dry skin, general weakness. From the anamnesis it is known that diabetes suffers for 3.5 years.

When examining a patient by the claimed method, it was revealed: during the test with an occlusion cuff, an increase in the tortuosity of the capillaries, perivascular edema was noted. SaO ₂ - 89%, t _approx. - 18 sec. SaO _hall. - 95%, t _cold. - 4 min 45 sec. SaO _2tem. decreased to 96%, t _heat. - 4 min 10 sec. SaO ₂ up 87%, at _up 13 s.

Conclusion: the initial stage of diabetic microangiopathy.

Example 2

Patient M., 18 years old, with a diagnosis of type I diabetes, severe form, decompensation phase. Diabetic nephropathy, stage microalbuminuria. Diabetic retinopathy, non-proliferative stage. Diabetic distal polyneuropathy, sensory form. Hypertrophic lipodystrophy. " On admission, she complained of polyuria, thirst, loss of appetite, weight loss, dry skin, general weakness. From the anamnesis it is known that the patient suffers from diabetes for 6 years.

The inventive method for the diagnosis of microangiopathy revealed a pronounced decrease in SaO _2occl. up to 83%; t _approx. - 28 sec When tested with a cold exposure SaO _2hol. - 88%, t _cold - 5 min 40 sec; heat sample - SaO _2tepl. - 91%, t _heat. - 4 min 40 sec. The test with raising the limb up revealed a decrease in SaO _{2 up} to 76% and elongation t _upx up to 21 sec.

Conclusion: a moderate stage of diabetic microangiopathy.

The above examples indicate the effectiveness of the proposed method for the diagnosis of microangiopathy in patients with diabetes.

Using the proposed method allows to identify both structural and functional changes of capillaries, to assess their severity and establish the level of reserve capabilities of capillaries, makes it possible to comprehensively assess the state of the microvasculature.

The advantages of the method compared to the prototype method are the high accuracy of determining microangiopathy at the initial stage of the disease, the ability to evaluate the various stages of microangiopathy, and the availability of widespread use in outpatient settings by general practitioners.

This method is applicable in patients in the early stages of diabetes mellitus, which makes it possible to widely use it for a short duration of the disease, when standard capillaroscopy does not reveal pathological changes.

The inventive method is tested in clinical practice and can be recommended for implementation in hospitals.

Claims (1)

A method for diagnosing microangiopathy in patients with diabetes mellitus, including conducting capillaroscopy at rest followed by an assessment of structural changes in the state of capillaries, characterized in that they additionally carry out capillaroscopy and oxygenometry with four functional tests with the influence of physical factors on the limb under study - cuff occlusion, a cold test, sample with thermal action, sample by raising the limb up, and after each of the samples was determined oxygenation index SaO ₂ and vre I capillaroscopy recovery performance to baseline values t, after occlusion cuff - SaO _2okkl. and t _approx. , after cold exposure - SaO _2hol. and t _cold. after heat exposure - SaO _2tepl. and t is _warm. , after raising the limb up - SaO _{2 up} and t _upx , and diagnose the initial stage of microangiopathy with SaO _{2 occl.} - 85-90%, t _approx. <20 seconds, SaO _2chol. > 95%, t _cold. <5 minutes, SaO _2tem. > 95%, t _heat. <4 minutes 30 seconds, SaO _{2 up} - 85-90%, t _upx <15 seconds, a moderate stage of microangiopathy is diagnosed with SaO _{2 occl.} - 80-85%, t _approx. - 20-30 seconds; SaO _2hol. - 87-95%, t _cold. - 5 minutes - 6 minutes 30 seconds; SaO _2tem. - 90-95%, t _heat. - 4 minutes 30 seconds - 5 minutes; SaO _{2 up} - 78-85%, t _upx - 15-25 seconds, diagnose a pronounced stage of microangiopathy with SaO _2occl. <80%, t _approx. > 30 seconds; SaO _2hol. <87%, t _cold. > 6 minutes 30 seconds; SaO _2tem. <90%, t _heat > 5 min; SaO _{2 up} <78%, t _up > 25 seconds.