Gorshunska M. Insulin resistance and adipocytokines in type 2 diabetes mellitus: pathogenetic role in the cardiovascular risk formation and the basis for therapy optimization

The object of the study: Туре 2 diabetes mellitus (T2D). Objective: to study pattern of cardiovascular risk factors (insulin resistance, low intensity inflammation, adipokines dysbalance, endothelial dysfunction) adjusted for glycemic control and genetic background (allele variants of adiponectin and paraoxonase candidate genes) in patients with T2D for further therapeutic intervention improvement based on detection of risk factors complex. Methods and equipment: anthropometric, clinical, biochemical, genetic, molecular-genetic, immunoenzymatic, instrumental and statistical; auto analyzer «Hitachi 912», preset thermo cycler «Biometra», US-scanner «Aloka», DNA-sequenator «Genetic Analyser 3130».Theoretical and practical results: based on revealed relationships of insulin resistance, adipose tissue endocrine dysfunction, low intensity inflammation, impaired metabolic homeostasis with the determining the contribution of allele variants of adiponectin and paraoxonase candidate genes up-to-date thoughts as to the pathogenesis of Type 2 diabetes and macrovascular complications are presented. It was proved the prospects of adopted Mediterranean-style diet use and omega-3 polyunsaturated fatty acids for improvement of the antidiabetic therapy effectiveness. Novelty: build up a concept of modulating role of impaired hormonal and metabolic homeostasis (hyperinsulinemia, hyperglycemia, dyslipidemia) in formation of high atherogenic potential in patients with T2D with regard to main insulin resistance factors (dysadipokinemia, obesity, low intensity inflammation) and allele variants of adiponectin and paraoxonase candidate genes. It was demonstrated the role of genetic variants of above-mentioned genes in the formation of the therapeutic efficacy of add-on therapy in patients with T2D and proved the possibility of their usage for genetic testing of hereditary susceptibility to T2D by evaluation of disease risk odds ratio in Ukrainian population. Degree of implementation: Practical recommendations were implemented into clinical practice of hospitals, research institutions and clinical departments. The main theses of dissertation were proposed for use in the educational process at the Department of endocrinology and pediatric endocrinology of Kharkiv Postgraduate Medical Academy. Area of application: endocrinology.