Role of adipose tissue hormones in the genesis of insulin resistance in patients with hypertension and type 2 diabetes mellitus

Adipose tissue is the main source of energy and plays an important role in the regulation of the body's energy homeostasis. Currently, the study of adipose tissue endocrinology is an area of close research and new discoveries that have allowed us to consider adipocytes as highly active endocrine cells secreting a number of chemokines, cytokines and peptides that directly or indirectly affect insulin resistance (IR), the rate of progression of atherosclerosis and vascular complications of diabetes mellitus (DM) in patients with hypertension (HT).

Based on their involvement in modulating insulin activity, 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).

Adiponectin is a specific adipokine. Numerous scientific studies have shown that the expression, secretion and plasma levels of adiponectin are reduced in obesity and abdominal distribution of adipose tissue, diabetes mellitus and hypertension.

The participation of resistin in the stimulation of inflammation mechanisms, activation of endothelium and proliferation of vascular smooth muscle cells makes it possible to consider it as a marker or even an etiologic factor in the development of diseases. It affects fat metabolism by the feedback principle: on the one hand, its concentration increases during adipocyte differentiation, on the other hand, resistin suppresses adipogenesis. Resistin as a cause of IR may be a link between obesity and the development of diabetes mellitus and hypertension. At the present stage, the biological and pathophysiological effects of resistin in the human body have not been fully clarified and this issue remains a 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, and type 2 diabetes mellitus. The increasing prevalence of obesity among people, the growing number of patients with complicated forms of the disease (impaired carbohydrate metabolism, IR, dyslipidemia, hypertension) explain the significant interest of doctors 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 the endocrinology of adipose tissue opens up opportunities to search for new points of influence in the prevention and treatment of diabetes mellitus, hypertension, and their complications in medical practice. The final clarification of the mechanisms of energy homeostasis disorders will allow for effective, individually tailored therapy based on the physiological characteristics of adipose tissue metabolism.

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

The study included 105 patients (41 men and 64 women), the average age of which was 65.16±1.53 years. All patients with hypertension were divided into 2 groups: the 1st group consisted of patients with hypertension and type 2 diabetes mellitus (n = 75), the 2nd group - patients with hypertension without type 2 diabetes mellitus (n = 30). The average age of patients with hypertension and type 2 diabetes mellitus was 65.45±1.08 years, and in the 2nd group - 64.87±1.98 years. The control group consisted of 25 practically healthy individuals. The diagnosis of hypertension and diabetes mellitus was verified in accordance with the current criteria.

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

Blood pressure (BP) was assessed as the mean BP obtained from three measurements at 2-minute intervals in a sitting position.

Body mass index (BMI) was determined using the formula:

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

Normal BMI values are up to 27 kg/m2.

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

IR = (fasting glucose x fasting insulin) / 22.5.

Determination of the content of glycosylated hemoglobin (HbAlc) in whole blood was carried out by a photometric method using a reaction with thiobarbituric acid using a commercial test system from the Reagent company (Ukraine) in accordance with the attached instructions.

The glucose level was determined by the glucose oxidative method in capillary blood taken on an empty stomach. The normal glucose level was considered to be 3.3-5.5 mmol/l. If the value of this indicator was more than 5.6 mmol/l, detected after two-fold measurement within 2-3 days, a consultation with an endocrinologist was prescribed.

The level of insulin in the blood serum was determined by the enzyme immunoassay using the ELISA kit (USA). The expected range of insulin values in the norm is 2.0-25.0 μU/ml.

Determination of the level of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and the atherogenic index (AI) were performed in blood serum using the enzymatic photocolorimetric method using kits from the company "Human" (Germany).

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

The obtained results are presented as the mean value ± standard deviation from the mean value (M±SD). Statistical data processing was performed using the Statistica package, version 8.0. The assessment of differences between groups with a distribution close to normal was performed using the Student criterion. Pearson correlation coefficients were calculated to analyze correlation relationships. Differences were considered statistically significant at p < 0.05.

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

Resistin levels increased in the group of hypertensive patients with type 2 diabetes mellitus compared with patients without diabetes mellitus and the control group, indicating that resistin may be a trigger factor for the development of metabolic disorders associated with diabetes mellitus.

Changes in adiponectin were in the opposite direction: its level significantly decreased in the group of hypertension with type 2 diabetes mellitus, which coincides with data from other researchers who admit that the development of insulin-independent diabetes mellitus may be associated with a violation of the regulation of adiponectin secretion, which normally inhibits glucose synthesis by the liver.

No statistically significant differences were found in the lipid metabolism parameters in patients of groups 1 and 2, namely, such as TC, HDL-C, LDL-C, VLDL-C, CA, which indicates dyslipidemic disorders in patients with hypertension, regardless of the presence of type 2 diabetes mellitus. However, with diabetes mellitus, these parameters are higher than without it, but these values are not reliable (p> 0.05). It should be noted that the levels of TG concentrations significantly differed between patients with and without diabetes mellitus and the control group (p< 0.05).

When distributing patients depending on the presence of type 2 diabetes mellitus, a clear tendency towards deterioration of carbohydrate metabolism was observed in parallel with an increase in blood glucose levels in individuals with hypertension.

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

Ranking of the studied factors by the degree of potentiation of disturbances in the level of adipose tissue hormones, carbohydrate and lipid metabolism using the t-criterion established that the most important potentiator of IR is type 2 diabetes mellitus. Then in the hierarchy follows resistin, AG, adiponectin and TC.

These factors were combined differently in each patient and caused a disruption of carbohydrate and lipid metabolism, which led to IR and subsequently to an increase in cardiovascular risk.

To study the relationships between adipose tissue hormones and clinical and metabolic parameters in groups of patients with hypertension with and without concomitant type 2 diabetes mellitus, a correlation analysis was performed with the calculation of Spearman correlation coefficients.

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

We also established reliable positive correlations between resistin and HbA1c (r = 0.57, p < 0.05), HDL-C (r = 0.29, p < 0.05) and the HOMA index (r = 0.34, p < 0.05), as well as negative ones between adiponectin and the HOMA index (r = -0.34, p < 0.05). The data obtained indicate that with hyperresistinemia and hypoadiponectinemia, which arose against the background of type 2 diabetes mellitus and hypertension, the insulin level increases and IR phenomena increase.

As a result of the research conducted, the following conclusions can be drawn.

In patients with hypertension and 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 found.

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

The established correlations confirm the aggravating influence of individual risk factors on the expression of total cardiovascular risk.

The obtained results should be taken into account in the treatment of patients with hypertension and type 2 diabetes.

O. I. Kadykova. The role of adipose tissue hormones in the genesis of insulin resistance in patients with hypertension and type 2 diabetes // International Medical Journal No. 4 2012