CLINICAL SIGNIFICANCE OF RETINOL BINDING PROTEIN-4 (RBP-4) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE
Abstract
Introduction. Retinol binding protein-4 (RSP-4) — a member of the adipokine family, synthesized in hepatocytes and adipocytes, is a transport protein for retinol; increases in patients with obesity, type 2 diabetes mellitus (type 2 diabetes), non-alcoholic fatty liver disease (NAFLD), indicates high cardiometabolic risks (CMR). RSP is recognized as a hormone of metabolic syndrome (MS) due to its effect on the main definitions of MS — visceral obesity, insulin resistance (IR), arterial hypertension (AH), dyslipidemia (DL). A high associative relationship of RSP-4 with the metabolic function of short-chain fatty acids (SCF) and free fatty acids (FFA) was revealed. With an excess of FFA, the binding of insulin to receptors of hepatocytes and other tissues decreases, hyperinsulinemia develops in conditions of IR. RSP-4 regulates the action of insulin in tissues, skeletal muscles and liver, has competence in relation to markers of inflammation — endotoxin (ET) and nitric oxide (NO), lipoprotein-associated phospholipase A2 (PLA2), which is a lipolytic enzyme that causes lipid modification and stimulates development of inflammation. The degree of IR may be due to the content of products of excessive glycosylation, in particular, an increased content of methylglyoxal (MG), which characterizes the metabolic memory of the cell and is regulated by the activity of RSP-4, causes an increase in the content of inflammatory markers, is accompanied by an increase in the activity of liver enzymes, the severity of morphological changes in hepatocytes, which negatively affects on the effectiveness of hypoglycemic drugs metabolizing in the liver, and can also cause unpredictable drug damage to the liver, which can lead to a more severe clinical course of type 2 diabetes and its multiple complications. A dynamic study of the content of RSP-4 will allow monitoring the effectiveness of antihyperglycemic drugs of various pharmaceutical groups, monitoring and anticipating the development of negative cardiovascular events and timely prophylaxis. Aim. To clarify the role of CBP-4 in assessing the clinical course of type 2 diabetes and cardiometabolic risks (CMR), to determine the prognostic value in patients with NAFLD and type 2 diabetes depending on the stage of the disease (hepatic steatosis or steatohepatitis). Materials and methods. 225 patients with disorders of carbohydrate metabolism (CMD) and NAFLD were examined. Mean age 57.3±5.2 years. Of these, 76 patients with type 2 diabetes and 132 with impaired glucose tolerance (IGT). body weight (BMI) was found to be more than 30 kg/m2 Index (34.85±1.79). The diagnosis was verified by manipulations, biochemical, instrumental and morphological research methods. Research results and discussion. Of the 225 observed in 74 patients with NAFLD, the content of insulin in the blood serum was observed by chemiluminescent immunoassay. The insulin level in the control group was 8.53±1.3 μIU/ml, in the group of patients with type 2 diabetes, NAFLD with hepatic steatosis — 16.28±0.4 μIU/ml, in the group of patients with type 2 diabetes + NASG — 34.65±4.16 μIU/ml. RSP-4 was determined in 89 patients by the enzyme immunoassay in blood serum In the control group (n=15) RSP-4 amounted to 26.15±1.31 μg/l, while in the group of type 2 diabetes + NASH (n=25) the indicator was 55.83±2.92 μg/l (p=0.001). In the group of type 2 diabetes + hepatic steatosis (n=49), the RSP-4 index of carbohydrates was 30.54±0.87 μg/l (p=0.001 compared to the control group). The highest le vels of methylglyoxal were found in patients with type 2 diabetes with NASH. The results of a study of nitric oxide in the blood serum of patients with type 2 diabetes with NAFLD compared with the control, high rates were found in patients with NAFLD, especially in the stage of steatohepatitis. In patients with type 2 diabetes and NASH, lipoprotein-associated phospholipase A2 is significantly increased.
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