Abstract
Abstract. This article presents the results of a comprehensive clinical genetic study conducted as part of a three-year research project at the Department of Age-Related Endocrinology and Clinical Pharmacology of the SI «V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine».
The study aimed to evaluate the prognostic significance of folate cycle gene polymorphisms (MTHFR, MTR, MTRR), biochemical markers of homocysteine metabolism, serotonin levels, hormonal status, concentrations of short-chain fatty acids (SCFAs), and psychoemotional characteristics for risk stratification and personalization of therapeutic strategies in patients with type 2 diabetes mellitus (T2DM) in the post-COVID period.
Material and methods. The study involved 109 patients who had recovered from COVID-19 (75 people with T2DM and 34 without carbohydrate metabolism disorders). The examination included an analysis of clinical and anamnestic data, anthropometric parameters, hormonal and metabolic profile, folate metabolism indicators, neurotransmitter activity and psychoemotional state. Polymorphisms of MTHFR 677C>T, 1298A>C, MTR 2756A>G, and MTRR 66A>G genes were determined using real-time PCR. Levels of homocysteine, serotonin, folic acid, ST2, cortisol, and DHEA-S were measured using enzyme-linked immunosorbent and chemiluminescent assays. SCFA concentrations in fecal filtrates were analyzed
via gas chromatography. Psychoemotional status was assessed using validated psychometric scales. Statistical data processing was carried out taking into account the nature of the distribution, using parametric and nonparametric criteria, Scheffe’s correction, as well as methods of correlation and regression analysis.
Results. Carriage of the T-allele of MTHFR 677C>T was significantly associated with elevated homocysteine levels, reduced folic acid and serotonin
concentrations, and adverse psychoemotional characteristics. In T2DM patients, elevated ST2 levels during the acute phase of coronavirus infection and their reduction in the post-COVID period during treatment with SGLT2 inhibitors, compared to individuals without diabetes, may serve as a marker of improved cardiovascular prognosis. The use of SGLT2 inhibitors and GLP-1 receptor agonists promoted a significant improvement in the metabolic and hormonal profiles, in particular the normalization of serotonin balance and markers of systemic inflammation compared to basic therapy.
Conclusions. A comprehensive analysis of genetic, neurotransmitter, hormonal, and behavioral determinants made it possible to identify the phenotypes of patients with an increased risk of ineffective response to treatment and justify the feasibility of a personalized approach to the management of type 2 diabetes in the recovery period after COVID-19.
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