Analysis of the formation of dysglycemia in the substantiation of early pathogenetic therapy of diabetes mellitus

Abstract

Introduction. To control carbohydrate metabolism disorders (CMD), which are closely related to the effect on the prognosis of cardiovascular diseases (CVD), their early, pathogenetically substantiated and prognosis-oriented therapy is required with a view to positive metabolic memory. The choice of drugs is based on the analysis of the formation of pre-nosological CMD - variants of prediabetes. The indices of the homeostatic model HOMA and the TyG family are most often used to assess the main links in the pathogenesis of CMD, IR and the secretory capacity of β-cells.Objective: to assess the basic pathogenetic links in prenosological CMD in comparison with type 2 diabetes mellitus (DM2) using a cohort of postmenopausal women: parameters of IR and secretory capacity of β-cells according to the TyG and HOMA-2 indices. Materials and methods. The examined 94 postmenopausal women 58.0 (53.0; 63.0) years old were divided into groups by history and HbA1c levels (%). Group 1 consisted of patients with T2DM (7.20: 6.60; 7.98) with a duration of 4.0 (2.0; 7.0) years; women with two-fold fasting normoglycemia without a history of CMD were classified according to their HbA1c levels into group 2 (prediabetes) and 3 (without CMD) twice: according to WHO criteria - 6.15 (6.03; 6.30) and 5.45 (5.20; 5.80); and ADA - 6.00 (5.80; 6.23) and 5.35 (5.05; 5.40), respectively. The indices TyG, HOMA2-IR, HOMA2-%S, and HOMA2-%B were determined (based on C-peptide calculations).Results and discussion. The performed analysis confirms the contribution of IR/insulin sensitivity to the progression of CMD with the participation of the phenomenon of lipoglucotoxicity at the prenosological stage of their formation, starting with HbA1c ≥ 5.7% levels. The inadequate secretory response of β-cells reflects an early decline in their functional abilities even at the stage of prediabetes. This limits the effectiveness of the classical stepwise scheme for intensifying glucose-lowering therapy with a T2DM duration of less than 10 years.Conclusions. Along with the timely diagnosis of dysglycemia, to control the cardiometabolic risk, it is advisable to use drug combinations early in terms of their effect on the key links in the pathogenesis of CMD: insulin resistance and β-cell dysfunction. Pioglitazone has been substantiated as an insulin sensitizer, which has a proven effect on the regression of early CMD and a decrease in the risk of cardiovascular events. In order to eliminate incretin dysfunction, which is closely related to the adequacy of the secretory capabilities of β-cells to the needs of impaired glucose homeostasis, a rational combination with an inhibitor of dipeptidyl peptidase-4.