MECHANISMS OF THE INFLUENCE OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS ON LDL RECEPTOR FUNCTION AND CARDIOVASCULAR RISK IN TYPE 2 DM (literature review)

Abstract

In the modern world, the prevalence of dysmetabolic conditions, which are accompanied by corruption of lipid metabolism and the distribution of adipose tissue in the body, is increasing, and their consequences include cardiovascular diseases, type 2 diabetes mellitus (T2DM) etc. These pathologies are characterized by dyslipidemia, which reflects an imbalance in the processes of assimilation, transportation, absorption and use by fatty acids’ cells as energy and plastic substrates. A decrease in the relative content of unsaturated fatty acids in low-density lipoproteins (LDL) causes dysfunction of cell membranes, and an increase in serum concentration of LDL means corruption of their absorption by cells, which contributes to the development of atherosclerosis. Absorption of LDL by cells occurs through the interaction of apolipoprotein apoE/B-100 with the membrane receptor of LDL. The cell regulates the supply of lipids and cholesterol by synthesizing these receptors. The expression of LDL receptors is regulated at the level of transcription; particularly, it is stimulated by insulin and suppressed by excess cholesterol, the latter leading to abnormal accumulation of lipids in cells and tissues and the development of pathology in various organs. According to clinical and experimental studies and meta-analyses, drugs from the group of inhibitors of sodium-dependent glucose cotransporter-2 (SGLT2) have a pronounced protective cardiorenal effect in patients with T2DM and in cases of kidney and heart dysfunction. These beneficial effects are associated with improving insulin sensitivity, increasing the level of antiatherogenic HDL cholesterol, reducing the accumulation of lipids in visceral fat, stimulating lipolysis, and switching of oxidation towards the preferential use of lipid substrates. The paradoxical increase in LDL cholesterol is mainly due to less atherogenic large floating particles, and the negative effect is apparently counterweight by the wide range of beneficial pleiotropic effects of gliflozins.