THE INFLUENCE OF ATORVASTATIN ON OMENTIN-1 LEVEL AND INSULIN RESISTANCE IN PATIENTS WITH CORONARY ARTERY DISEASE AND OBESITY

Adipose tissue is a powerful endocrine organ, which synthesizes significant amount of biologically active substances – adipokines. Due to adipokine dysfunction, a spectrum of diseases associated with obesity appears, namely, coronary artery disease, diabetes mellitus, hypertension and oncology. Hyperinsulinemia and insulin resistance play a significant role in pathogenesis of cardiometabolic complications in patients with obesity. They trigger a pathological cascade of reactions leading to cardiovascular diseases. Omentin-1 possesses anti-atherogenic action and it can modify peripheral effects of insulin. The aim of the study – to analyze changes in omentin-1 concentration and the condition of insulin resistance in patients with coronary artery disease and obesity during atorvastatin treatment. Materials and Methods. 55 patients with obesity were examined. They had general clinical examination; blood lipids, uric acid level and liver enzymes; glycated hemoglobin, glucose, insulin with the calculation of HOMA index and omentin-1 concentration was determined. Patients were divided into two groups: the group 1 – 20 patients with obesity, who did not suffer from CAD and did not take atorvastatin, and the group 2 – patients with CAD and obesity, who took atorvastatin. Determination of these indices was performed for patients of the group 2 in dynamics in 12 months. Results and Discussion. In the group of patients with CAD and obesity, who took atorvastatin, lipid levels were reliably lower, but levels of fasting glucose concentration, uric acid and liver enzymes were higher than in the patients who did not take the drug. Elevation of omentin-1 in blood serum was observed in 12 months in patients with CAD and obesity simultaneously with the increase in insulin level and the decrease in tissue sensitivity to it. Conclusions. Intake of atorvastatin by patients with coronary artery disease and obesity is accompanied by elevation of insulin concentration, intensification of insulin resistance and increase in omentin-1 level.

INTRODUCTION Adipose tissue is a powerful endocrine organ that synthesizes significant amount of biologically active substances -adipokines, which can influence energy homeostasis, carbohydrate and lipid metabolism, blood pressure, angiogenesis, coagulation and functioning of the immune system. Due to adipokine dysfunction, a spectrum of diseases occurs, associated with obesity, namely, coronary artery disease, diabetes mellitus, hypertension and oncology.
Hyperinsulinemia and insulin resistance play a significant role in pathogenesis of cardiometabolic complications in patients with obesity. They trigger a pathological cascade of reactions leading to cardiovascular diseases. Omentin-1 possesses anti-atherogenic action and it can modify peripheral effects of insulin [2].
Omentin-1 has a direct influence on inflammation and damage to the epithelium and increases transportation of glucose, stimulated by insulin, in adipocytes; it is considered a biomarker of obesity, atherosclerosis, insulin resistance, and type 2 diabetes mellitus. Thus, the decrease in its concentration is associated with the afore mentioned conditions [3].
In their research, ChenQianqian and co-authors observed dose-dependent elevation of omentin-1 level in patients with CAD during intake of atorvastatin [4]. Thus, the study of interconnection of omentin-1 level and insulin resistance in patients with CAD and obesity is a topical issue.
The aim of the study -to analyze changes in omentin-1 concentration and insulin resistance in patients with coronary artery disease and obesity during atorvastatin treatment.
MATERIALS AND METHODS 55 overweight or obese patients were selected for investigation. Patients were divided into two groups: the group 1 included 20 patients with obesity without clinical signs of CAD, and the group 2 -35 patients with CAD and obesity, who took atorvastatin. The groups were equal by gender and age. The degree and type of obesity were determined by WHO criteria and IDF (2015).
Diagnosis of CAD was considered verified by the results of coronarography and/or the presence of myocardial infarction in anamnesis more than three months before. Treatment of patients with ischemic heart disease was administered according to unified clinical protocol "Stable coronary artery disease" approved by the Ministry of Health of Ukraine No. 152, dated 02.03.2016(with amendments 23.09.2016, including atorvastatin in the dose 20-40 mg, patients of the group 1 did not take statins. Lipid blood spectrum, biochemical indices and glycated hemoglobin (HbA1 C ) were detected by generally accepted methods on automatic analyzer "BioSystems" (Spain) using original sets of reagents. The level of insulin in blood serum was determined on immunochemoluminescence analyzer "Immulite 2000" (Siemens, Germany) using proper reagents (Immulite 2000 Insulin, USA).
Indices of lipid, carbohydrate blood spectrum, liver enzymes, uric acid and omentin-1 in patients with CAD and obesity, taking atorvastatin (group 2), were determined in dynamics in 12 months of monitoring.
The results are given as mean values with statistical error. The values with normal distribution are presented as confidence interval (95 %); and the values, where distribution significantly differed from the norm, are presented as interval of 25 % and 75 % percentiles. Comparison of groups was performed by means of Mann -Whitney U-test. The results were considered statistically reliable at р< 0.05.

RESULTS AND DISCUSSION
As it is seen from Table  1, indices of transaminases, uric acid and glucose were reliably higher in the first group of patients with CAD and obesity, who took atorvastatin, unlike patients from the second group, who demonstrated higher BMI and waist circumference indices. The levels of triglycerides and glycated hemoglobin in the investigated groups reliably did not differ. Concentration of low-density lipoproteins, high-density lipoproteins and total cholesterol was reliably higher in the group of patients, who did not take atorvastatin.
In the group 2, reliable changes in lipid spectrum of the blood, liver transaminases and uric acid were not observed in a year of monitoring. Concentration of fasting blood glucose level and glycated hemoglobin almost did not change; however, insulin level increased almost twice, which provoked increase in HOMA-IR index.
Despite numerous advantages of statin therapy for cardiological patients, one of the negative influences on metabolism is the ability of atorvastatin to intensify insulin resistance and induce type 2 diabetes mellitus. Thus, patients with risk factors of type 2 diabetes mellitus development need thorough monitoring of glucose metabolism during hypolipidemic therapy.
The level of omentin-1, which is an anti-atherogenicadipokine, reliably increased throughout 12 months of atorvastatin intake in the dose of 20-40 mg by patients with CAD and comorbid obesity from 0.87 ng/ml to 1.60 ng/ml, p<0.05 (Fig.2).
The obtained results enable to suppose two possible mechanisms of omentin-1 increase in these patients: a direct influence of atorvastatin or elevation of omentin-1 is of compensatory nature as a response to intensification of insulin resistance, most likely induced by the same atorvastatin. It should be noted that type 2 diabetes mellitus was diagnosed for the first time in two patients from the group 2 in 12 months of monitoring. Omentin-1 level in these patients constituted 0.26 and 0.086 ng/ml before onset of type 2 diabetes mellitus, which may indicate exhaustion of compensatory mechanisms for the regulation of insulin resistance indirectly via omentin-1.
CONCLUSIONS 1. In patients with CAD and obesity, who took atorvastatin, lipid spectrum was better than in patients with obesity without CAD and drug intake, however, the  Email address for correspondence: maksymets.t@gmail.com