FEATURES OF EXCRETION OF MELATONIN IN URINE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE WITH MANIFESTATIONS OF FIBROSIS AND ITS RELATIONSHIP WITH CERTAIN METABOLIC AND IMMUNOLOGICAL INDICATORS.

To study the features of secretion of melatonin in the urine in patients with DM type 2 and NAFLD with manifestations of fibrosis and its relationship with some metabolic and immunological parameters, 23 patients with DM type 2 and NAFLD were examined. The degree of fibrosis in patients was diagnosed on the basis of static elastography and the study of indirect fibrosis markers 16 persons (72%) diagnosed with mild fibrosis (F0-F1 on METAVIR), 5 people (18.2%) - with moderate fibrosis (F2-F3 on METAVIR). Only 2 (8.7%) patients did not have any fibrotic disorders, so they were excluded from the further study. All patients underwent determination of melatonin excretion of albumin and in daily urine, as well as the determination of homocysteine in the blood. The level of excretion of melatonin in the urine in patients with DM type 2 and NAFLD did not depend on the degree of fibrosis and on the average was 89.50±16.66 mmol/day, which exceeded the reference values. It has been established that the increase in melatonin level in patients with DM type 2 and NAFLD is associated with the presence of fibrotic changes in the liver and a decrease in the activity of the inflammatory process. In addition, a direct correlation was found between the excretion of melatonin and homocysteine (r=0.43), as well as between melatonin and albumin excretion in the urine (r=0.20). Thus, an increased level of excretion of melatonin in the urine can be not only a marker of liver fibrosis, but also a predictor of cardiovascular disorders in patients with DM type 2 and NAFLD.

[ADIPONECTIN AND A VIOLATION OF METABOLIC CONTROL AT DIFFERENT STAGES OF NONALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH TYPE 2 DIABETES].

One of the urgent problems of Endocrinology is the study of the mechanisms of formation and progression of nonalcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus (DM) type 2. Prognosis depends on the stage of NAFLD in which the changes occur and secretion of adipocytokines in the first place, adiponectin. The aim of the study was to: define adiponectin levels in the circulation of patients with type 2 diabetes at different stages of NAFLD and its impact on the detection of metabolic changes, the establishment of linkages with carbohydrate, lipid, protein metabolism, and liver function. The study determined the relevance of the study of pathogenetic mechanisms of NAFLD in the future, because the violation of metabolic control and reduce the protective properties of adipocytokines in patients with comorbid disorders is of great interest to further improve diagnostic capabilities, prevent complications and improve the quality of life of these patients.

[Mechanisms of formation and progression of non-alcoholic fatty liver disease in type 2 diabetics].

Currently, study of the mechanisms of formation and progression of non-alcoholic fatty liver disease (NAFLD) in the patients with type 2 diabetes mellitus (DM) is a topical problem in endocrinology. Prognosis for the disease depends on NAFLD stage and it determines the necessity to study the origin and mostly the progression in NAFLD course. It will favour the enhancement of efficacy of the treatment for this cohort of patients. The object of this work was to study the mechanisms of formation of NAFLD phasic course in type 2 diabetics via determining the levels of lipid peroxidation (LPO), 8-isoprostaglandin as components of oxidative stress. LPO indices and liver functional activity parameters (general cholesterol, high-density lipoproteids cholesterol, triglycerides, ß-lipoproteids, very-low-density lipoproteids cholesterol, atherogenicity coefficient, thymol test, alanine aminotransferase, aspartate aminotransferase) were determined in the examined individuals. The carried research allowed, that changes in biochemical parameters levels is connected with increasing of diene conjugates (DC) activity and the carried correlation analysis of the studied values proved this relevance. The subgroup of the patients with DC levels of 200-400 nmol/l has no inflammatory alterations (cytolysis syndrome) that gives evidence of steatosis phase. The group of patients with DC levels of 400-600 nmol/l demonstrated the stage of non-alcoholic steatohepatitis with the most expressed shifts in functional liver condition. The greatest lipid, carbohydrate metabolic changes were found in the subgroup of the patients with DC level of 600 nmol/l and more that gives evidence of fibrotic processes.

[The structure of type 2 diabetes risk-factors in people with normal weight].

In the current study we have presented the analyzed data of screening materials of type 2 diabetes patients aged 45 and above carried out in Kharkov (n=535) and Kharkov district villages (n=1052). It has been established, that the data of cohort people with normal body mass index were practically the same and accounted approximately one fourth of the analyzed patients. At the same time, it appeared that the patients living in the city were more susceptible to metabolic obesity (enlargement of abdominal fat tissue), arterial hypertension, myocardial infarction, insult and heavy family history. Metabolic obesity prevalent in city cohorts practically did not have any effect on the frequency of the above mentioned risk-factors. However, it definitely affected the cardio-vascular component in village cohorts.

[Biological role of fetuin A and its potential importance for prediction of cardiovascular risk in patients with type 2 diabetes mellitus].

The authors' data and those from literature concerning biological role of fetuin A glycoprotein have been generalized in the article. A direct correlation has been established between fetuin A and some adipokines involved in the formation of insulin resistance and atherogenesis (progranulin, omentin-1), and osteoprotegerin (the novel cardiovascular risk factor) as well as an increase of circulating levels of fetuin A in patients with type 2 diabetes mellitus with high cardiovascular risk metabolic pattern but without manifestations of macrovascular complications. This substantiates the involvement of fetuin A in the complex of biomarkers of subclinical atherosclerosis.

[Q192R polymorphism of PON-1 gene in type 2 diabetic patients].

Polymorphism of PON-1 gene in 192 position of amino acid sequence of enzyme paraoxonase 1 was studied. For this research we have used the blood samples of 96 patients with T2DM and 123 healthy habitants of Kharkiv. Frequencies of alleles for the patients (pQ = 0,65, pR = 0,35) and the healthies (PQ = 0,70 and pR = 0,30) did not differentiate meaningfully. Distribution of the genotypes for healthy people does not correspond to Hardy-Weinberg equilibrium, the patients of T2DM have surplus of both homozygotes and shortage of heterozygotes. The risk of illness of T2DM for QQ homozygotes is 1,46-times higher and for QR heterozygotes is two times lower than on the average in the population (2%). The risk of illness of T2DM for RR homozygotes 1,86-times exceeds a middle population risk but is not significant.

[Study of genetic determination of base clinical components of metabolic syndrome].

Genetic analysis was carried out on the material including clinic and genealogical data about 510 patients with type 2 Diabetes Mellitus, 445 Essential Hypertension individuals, 239 abdominal obesity persons and their 1st degree relatives. It has been shown that the Essential Hypertension and abdominal obesity distribution in the population and families can be described by means of a variants polygene model with essential influence of the major genes. Gene complexes of predisposition to obesity, Essential Hypertension and Type 2 Diabetes Mellitus are independent, however, their liabilities are covered.

[Lipid peroxidation in patients with diffuse toxic goiter and hypothyroidism]. / Perekisnoe okislenie lipidov u bol'nykh diffuznym toksicheskim zobom i gipotireozom.

A study made in 77 patients with different form of thyropathy revealed increased blood plasma and erythrocyte content of lipid peroxidation products, such as diene conjugates and TBA-active producers. The plasma chemiluminescence got more intense as well. Different mechanisms for the lipid peroxidation activation in patients presenting with thyroid hormone abundance or deficiency have been analyzed.