The role of fatty tissue hormones in the genesis of insulin resistance in patients with essential hypertension and type 2 diabetes mellitus

Fatty tissue is the main source of energy and plays an important role in regulating the energy homeostasis of the body. At present, the study of endocrinology of adipose tissue is a field of close research and new discoveries that allowed to consider adipocytes as highly active endocrine cells secreting a number of chemokines, cytokines and peptides that directly or indirectly affect insulin resistance, the rate of progression of atherosclerosis and vascular complications of diabetes mellitus (DM) in patients with essential hypertension (GB).

Lipocytokines are conventionally divided into insulin sensitizers (leptin, adiponectin, insulin-like growth factor-1) and insulin antagonists (tumor necrosis factor-a, interleukin-6 and resistin) in the modulation of insulin activity.

Adiponectin is a specific adipokine. Numerous scientific studies have proved that expression, secretion and plasma level of adiponectin decrease with obesity and abdominal distribution of adipose tissue, diabetes and GB.

The involvement of resistin in stimulating the mechanisms of inflammation, endothelial activation and proliferation of smooth muscle cells of the vessels makes it possible to consider it as a marker or even an etiologic factor of the development of diseases. It affects fat metabolism on the principle of feedback: on the one hand, its concentration increases when differentiating adipocytes, on the other - resistin suppresses adipogenesis. Resistin as a cause of IR can be a link between obesity and the development of diabetes and hypertension. At the present stage, the biological and pathophysiological effects of resistin in the human body are not fully understood and this topic remains the topic of discussion.

Thus, adipose tissue is an active metabolic and endocrine organ that plays a key role in the development of obesity, metabolic syndrome, type 2 diabetes mellitus. An increase in the prevalence of obesity among people, an increase in the number of patients with complicated forms of the disease (a violation of carbohydrate metabolism, IR, dyslipidemia, GB) explain the significant interest of physicians in understanding the physiology of adipose tissue and in particular the role of adipokines in the development and progression of metabolic disorders. A better understanding of endocrinology of adipose tissue opens the possibility of finding new points of influence in the prevention and treatment of diabetes mellitus, hypertension and their complications in medical practice. The final refinement of the mechanisms of the disturbance of the energy homeostasis will allow to carry out an effective individually selected therapy based on the physiological features of fat metabolism.

Therefore, the purpose of this study was to study the role of fatty tissue hormones in the genesis of insulin resistance in patients with essential hypertension and type 2 diabetes mellitus.

The study included 105 patients (41 men and 64 women) whose mean age was 65.16 ± 1.53 years. All patients with hypertensive disease were divided into 2 groups: the first group consisted of patients with type 2 diabetes mellitus (n = 75), the second group consisted of patients with type 2 diabetes (n = 30). The mean age of hypertensive patients with type 2 diabetes mellitus was 65.45 ± 1.08 years, and in the second group, 64.87 ± 1.98 years. The control group consisted of 25 practically healthy persons. The diagnosis of hypertension and diabetes mellitus was verified according to the current criteria.

The study did not include patients with hypertensive disease with acute or chronic inflammatory, oncological diseases, renal insufficiency and insulin-dependent diabetes.

The blood pressure level (BP) was assessed by the average BP, obtained as a result of three measurements at 2-minute intervals in the sitting position.

The body mass index (BMI) was determined by the formula:

BMI = weight (kg) / height (m2).

Normal values of BMI - up to 27 kg / m2.

To determine the IR, the HOMA-IR index was used (normal values up to 2.7), which was calculated by the formula:

IR = (fasting glucose x insulin on an empty stomach) / 22.5.

Determination of the content of glycosylated hemoglobin (HbAlc) in whole blood was performed by photometric method by reaction with thiobarbituric acid using the commercial test system of Reagent (Ukraine) in accordance with the attached instruction.

The glucose level was determined by the glucose oxidative method in capillary blood taken on an empty stomach. Normal was considered to be a glucose level of 3.3-5.5 mmol / l. With the value of this indicator more than 5.6 mmol / l, found after a two-fold measurement for 2-3 days, an endocrinologist was consulted.

The serum insulin level was determined by an enzyme immunoassay using the ELISA kit (USA). The expected range of insulin values is normal - 2.0-25.0 μED / ml.

Determination of the level of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL cholesterol), low density lipoprotein cholesterol (LDL cholesterol), very low density lipoprotein cholesterol (VLDL) and atherogenic coefficient (CA) enzymatic photocolorimetric method by the sets of the firm "Human" (Germany).

The content of resistin and adiponectin in the serum of patients was determined by the enzyme immunoassay on the enzyme immunoassay analyzer "Labline-90" (Austria). Resistance level studies were carried out using the commercial test system produced by BioVendor (Germany), the level of adiponectin - using a commercial test system manufactured by ELISA (USA).

The results are presented as the mean ± standard deviation from the mean (M ± SD). Statistical processing of data was carried out using the package Statistica, version 8.0. Estimation of differences between groups with a distribution close to normal was made using the Student's test. For correlation analysis, Pearson correlation coefficients were calculated. Statistically significant differences were considered for p <0.05.

When comparing the anthropometric parameters, there were no significant differences in age, weight, height, heart rate (heart rate), pulse, systolic (SBP) and diastolic blood pressure (DBP) between patients of both groups.

The level of resistin increased in the group of hypertensive patients with type 2 diabetes mellitus as compared to patients without diabetes mellitus and control group, which indicates that resistin can be a trigger factor in the development of metabolic disorders associated with diabetes mellitus.

Changes in adiponectin were reversed: its level significantly decreased in the hypertensive group with type 2 diabetes mellitus, which coincides with the data of other researchers who admit that the development of non-insulin dependent diabetes mellitus may be associated with a violation of the regulation of adiponectin secretion, which normally depresses synthesis of glucose by the liver.

There were no statistically significant differences in lipid metabolism in patients of groups 1 and 2, such as OXC, HDL cholesterol, LDL cholesterol, LDLP cholesterol, and CS, which indicates dyslipidemic disorders in patients with essential hypertension, regardless of the presence diabetes mellitus type 2. However, in diabetes mellitus, these indicators are higher than without it, but these values are not reliable (p> 0.05). It should be noted that the levels of TG concentrations were significantly different between patients with diabetes mellitus and without it and with a control group (p <0.05).

In the distribution of patients, depending on the presence of type 2 diabetes mellitus, there was a clear tendency to worsen carbohydrate metabolism in parallel with the increase in blood glucose level in people with hypertensive disease.

When studying the HOMA index, data were obtained on a significant increase (9.34 ± 0.54 as compared with 3.80 ± 0.24 and 1.94 + 0.12, respectively) in patients of the first group compared with the second group and the control group ( p <0.05).

Ranking of the studied factors by the degree of potentiation of violations of the level of hormones of adipose tissue, carbohydrate and lipid metabolism with the help of the t-test established that the most important potentiator of MI is diabetes mellitus type 2. Then, in order of hierarchy, resistin, AH, adiponectin and OXC are followed.

These factors were combined in different ways in each patient and caused a violation of carbohydrate and lipid metabolism, which led to RI and subsequently to an increase in cardiovascular risk.

To study the relationships of fatty tissue hormones with clinical and metabolic parameters in groups of patients with concomitant diabetes mellitus type 2 and without it, a correlation analysis was performed to calculate the Spearman correlation coefficients.

Positive correlations between adiponectin and BMI (r = 0.48, p <0.05) were determined, which coincides with the evidence that adiponectin decreases with hypertension and obesity, which leads to the progression of diabetic and atherosclerotic effects and increases the risk of unwanted cardiovascular events with a combination of hypertension, diabetes and obesity.

We also established reliable positive correlation links between resistin and HbA1c (r = 0.57, p <0.05), HDL cholesterol (r = 0.29, p <0.05) and HOMA index (r = 0.34, p <0.05), and also negative between adiponectin and HOMA index (r = -0.34, p <0.05). The data obtained indicate that hyperresistinemia and hypoadiponectinemia, which occurred against the background of type 2 diabetes mellitus and hypertensive disease, increase the insulin level and increase the phenomenon of IR.

As a result of the conducted researches it is possible to draw the following conclusions.

In hypertensive patients with type 2 diabetes mellitus, a significant increase in the levels of resistin, insulin, glucose, TG, HOMA index and a decrease in the level of adiponectin was established.

In the formation of IR, a leading role belongs to diabetes mellitus and adipose tissue hormones, such as resistin and adiponectin.

The established correlation links confirm the aggravating effect of individual risk factors on the expression of the total cardiovascular risk.

The results obtained should be taken into account in the treatment of patients with essential hypertension and type 2 diabetes mellitus.
 
OI Kadykova. The role of fatty tissue hormones in the genesis of insulin resistance in patients with essential hypertension and type 2 diabetes mellitus // International Medical Journal No. 4 2012