Kobyliak N. Clinical and experimental substantiation of complex treatment of type 2 diabetes mellitus and associated disease

The dissertation aimed to substantiate and develop a strategy to improve the treatment of patients with type 2 diabetes (T2D) and associated disease such as obesity and nonalcoholic fatty liver disease (NAFLD) by influencing the gut microbiota and developing new methods of prevention and treatment. The experimental part of the study was conducted in 2 stages. To study the effectiveness of probiotic therapy that is dependent on the composition and activity of a combination of different probiotic strains, a universal experimental model of obesity caused by neonatal administration (2-10 postnatal days) of monosodium glutamate (MSG) was employed in the dissertation. We subsequently suggested that enrichment of the alive multi-probiotic with nutraceuticals such as omega-3 polyunsaturated fatty acids (PUFAs) and enterosorbent smectite could lead to a summation of positive single effects. Experimental studies on the tested GIO model allowed us to determine the most effective courses of probiotics and nutraceuticals as well as their points of influence for prophylactic and curative use in managing the development of T2D, associated obesity and NAFLD; the studies also became the basis and justification of clinical trials. In 6 randomized placebo-controlled trials in patients with type 2 diabetes, administration of live multiprobiotics or their combination with nutraceuticals (omega-3 PUFA) or smectite as addition to standard antidiabetic therapy for 8 weeks, associated with significant reduction of IR, anthropometric parameters of obesity, fatty liver index, markers of liver functional activity and chronic systemic inflammation in the dynamics of treatment compared with placebo.