Features of microcirculatory disorders in patients with complicated diabetes mellitus

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Introduction

Among the complications of type 2 diabetes mellitus (T2DM), one of the severe ones is diabetic foot syndrome (DFS), and among microvascular complications — diabetic nephropathy [1–8].

Timely detection of changes in the microcirculatory bed has become the subject of numerous foreign and domestic studies. Against this background, the value of non-invasive methods for assessing blood flow (ultrasound dopplerography, laser Doppler flowmetry) with the use of functional tests (thermal, cold, cuff) is increasing. These tests are important for the early diagnosis of type 2 diabetes mellitus complications [9; 10]. According to the authors, the thermal test is more significant, as it allows for the timely detection of damage to fine fibres in patients with diabetes mellitus [11; 12]. An insufficient response to the tests indicates functional disorders, which play an important role in the development of diabetic complications [13]. The functional reactivity of microvessels can be considered a more sensitive indicator of diabetes complications compared to traditional methods [14]. It follows from the above how important it is to assess the degree of microcirculatory disorders using the method of local skin thermometry in patients with complicated diabetes mellitus.  

The objective of the study is to assess microcirculatory disorders in patients with diabetic nephropathy and diabetic foot syndrome using the method of local skin thermometry.

Materials and methods

To assess the state of microcirculatory disorders, the method of local skin thermometry was used with the «Microtest» device [15]. The device operates by registering low-amplitude fluctuations in skin temperature caused by changes in microvascular tone. The characteristics of the coefficients of relative changes in the amplitudes of oscillations (vasodilation indices) in the endothelial and neurogenic frequency ranges (Ke Kn) during the thermal test are given. In the process of statistical analysis of the results, the programs Statistica 6 and Microsoft Excel 7.0 for Windows XP were used. During the study, a set of criteria for a normal (Gaussian) distribution was used to determine the type of distribution of the quantitative trait: the mean value (M) and standard deviation (SD). For a “non-normal” distribution, the median (Me) and quartiles were used. The analysis was carried out according to the methods recommended in biomedical statistics.

Results and discussion

A total of 55 women with type 2 diabetes mellitus (group 1) who had diabetic foot syndrome were examined, 12 of them had a history of surgery. All patients were diagnosed with retinopathy and arterial hypertension. Diabetic polyneuropathy of the lower extremities was recorded in 100 % of cases. The average age was 65.5 [62; 74] years. The duration of the disease was 15 [10; 17.5] years, waist circumference (WC) — 100 [90; 109] cm, glycated haemoglobin HbA1c — 9.3 [8.5; 10.2] %.

The second group consisted of patients with diabetic nephropathy (DN) (n = 261). Arterial hypertension was recorded in 91 % of them. The average age was 60 [58.5; 66.5] years. The duration of the disease was 12.5 [10; 18] years, waist circumference — 101 [93.2; 109.5] cm, glycated haemoglobin HbA1c – 10.4 [9.4; 12.5] %. A slight decrease in GFR (Glomerular Filtration Rate) to the level of 60–90 ml/min/1.73 m² was recorded in 71.9 % of patients, and a moderate and significant decrease was recorded in 28.1 %.

The control group consisted of 125 patients (group 3) who did not have diabetes mellitus. The average age was 68 [61; 72.2] years. Waist circumference — 90 [89; 96.5] cm.

In patients with diabetic foot syndrome, a direct correlation was observed between HbA1c levels and BMI, as well as the duration of the disease (r = +0.5; р = 0.02; r = +0.4; р = 0.03). With an increase in HbA1c levels, an increase in the levels of atherogenic fractions of the lipid spectrum was noted: LDL cholesterol (r = +0.996; р = 0.0001), atherogenic index (r = +1.0; р = 0.0001). In patients of the first group, a direct statistically significant correlation was found between the indicators of tactile sensitivity of the lower extremities and the level of HbA1c (r = +0.4; р = 0.05). A statistically significant relationship was established between the indicators of pain and tactile sensitivity of the lower extremities and the duration of diabetes mellitus (r = +0.7; р = 0.001).

In women with diabetic nephropathy, a direct correlation was observed between HbA1c levels and proteinuria levels (r = +0.32; р = 0.04). A direct significant correlation was found between the indicators of the glycemic profile and blood creatinine levels in patients (r = 0.697, р = 0.001; r = 0.612, р = 0.01; r = 0.557, р = 0.02 respectively). An inverse relationship was established between GFR and fasting blood glucose levels, postprandial blood glucose (r = –0.689, p = 0.0016; r = –0.619, p = 0.01 respectively).

The vasodilation indices in the endothelial and neurogenic ranges in the compared groups are presented in Table 1.

 

Table 1 The values of vasodilation indices in the endothelial and neurogenic ranges in the study groups, conventional units

Frequency range	Group 1	Group 2	Control group	р
Ke	3.4 ± 0.77	1.2 ± 0.3	2.4 ± 0.5	р1–3 = 0.07; р 2–3 = 0.005*
Kn	3.2 ± 0.48	1.8 ± 0.4	2.8 ± 0.7	р1–3 = 0.08; р 2 = 0.004*

Note: * — the difference in indicators is statistically significant (p < 0.05).

 

The data in Table 1 show that the vasodilation indices in the endothelial and neurogenic frequency ranges were significantly lower in the group of patients with diabetic nephropathy than in the control group, which confirms the presence of severe endothelial dysfunction in this category of patients. Unlike group 1, patients with diabetic foot syndrome showed a tendency towards an increase in these indicators. The microcirculatory blood flow in the skin is controlled by sympathetic adrenergic vasoconstrictor nerve fibres and sympathetic vasodilator nerves through the opening and closing of arteriovenous anastomoses and precapillary arterioles [11]. At normal temperatures, the tone of the microcirculatory vessels is maintained by the vasoconstrictor system, with the arteriovenous anastomoses closed. On the one hand, the thermal test is one of the tests for the functional assessment of the microvascular bed, and on the other hand, it is a test for the early diagnosis of microcirculation disorders.

As a result of disorders of sympathetic innervation of blood vessels in the lower extremities, vasoconstriction decreases and vasodilator effects prevail in patients with diabetic foot syndrome. In addition, there is always an inflammatory component in diabetic foot syndrome. Based on the results obtained, this assumption can be made.

Correlation analysis showed an inverse relationship between indicators of carbohydrate metabolism, lipid spectrum, and amplitudes of skin temperature fluctuations in the endothelial, neurogenic, and myogenic frequency ranges (Table 2).

 

Table 2 The relationship between HbA1c levels, lipid spectrum, and vasodilation indices in the endothelial, myogenic, and neurogenic components in patients with type 2 diabetes mellitus and diabetic foot syndrome

Comparable values	r	р
НbА1с & Ke	–0.872	0.000*
НbА1с&Kn	–0.867	0.000*
НbА1с& Km	–0.648	0.005*
Postprandial glycaemia& Ke	0.946	0.000*
Postprandial glycaemia &Kn	0.527	0.026*
LDL cholesterol & Ke	–0.896	0.000*
LDL cholesterol & Kn	–0.858	0.000*
LDL cholesterol & Km	–0.871	0.000*

Note: * — the difference in indicators is statistically significant (p < 0.05).

 

From the data in Table 2, it can be seen that as the HbA1c level increased, the indicators in the neurogenic, myogenic, and endothelial frequency ranges decreased.

As LDL cholesterol increased, the indicators in the neurogenic, endothelial, and myogenic frequency ranges decreased.

An inverse relationship was found in the second group between Ke-indicators and age (r = –0,315; р = 0.02), and fasting blood glucose (r = –0.168; р = 0.02).

Conclusions

1. In patients with diabetic foot syndrome, carbohydrate metabolism disorders are associated with BMI, the duration of diabetes mellitus, indicators of atherogenic fractions of the lipid spectrum, tactile sensitivity of the lower extremities, and HbA1c levels (r = +0.4; p = 0.05). A connection was established between the indicators of pain sensitivity of the lower extremities and the duration of diabetes mellitus.
2. In patients with diabetic nephropathy, an inverse relationship was found between the indicator in the endothelial frequency range and age (r = –0.315; р = 0.02), and fasting blood glucose (r = –0.168; р = 0.02).
3. Vasodilation indices in all frequency ranges are inversely proportional to indicators of carbohydrate and lipid metabolism.
4. In patients with diabetic foot syndrome, disorders of carbohydrate metabolism are associated with body mass index, the duration of diabetes mellitus, indicators of atherogenic fractions of the lipid spectrum, and tactile sensitivity of the lower extremities.

About the authors

T. P. Demicheva

Ye.A. Vagner Perm State Medical University

Author for correspondence.
Email: demich-perm@mail.ru
ORCID iD: 0000-0002-5422-8700
SPIN-code: 3743-3914

PhD (Medicine), Associate Professor of the Department of Endocrinology and Clinical Pharmacology

Russian Federation, Perm

E. N. Смирнова

Ye.A. Vagner Perm State Medical University

Email: demich-perm@mail.ru
ORCID iD: 0000-0003-2727-5226

DSc (Medicine), Professor, Head of the Department of Endocrinology and Clinical Pharmacology

Russian Federation, Perm

References

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