THE ROLE OF ENDOTHELIAL DYSFUNCTION IN THE FORMATION OF COMPLICATIONS OF DIABETES MELLITUS AND THE PROSPECTS FOR ITS CORRECTION BY THE RECEPTOR ANTAGONIST INTERLEUKIN-1

Abstract

Diabetes mellitus (DM) is a steadily progressing disease that affects mainly people of working age and quickly leads to the development of systemic complications. DM takes the third place in the mortality statistics after cardiovascular and oncological diseases. The main cause of disability and mortality in diabetes are micro- and macrovascular complications, leading to the development of cardiovascular and cerebrovascular diseases. Diabetes is associated with an increased risk of developing myocardial infarction and ischemic stroke and with their less favorable outcome.

The aim of the study – to conduct a general review and theoretical analysis of representative facts in research of various aspects of the formation and progression of endothelial dysfunction in diabetes.

Materials and Methods. The article uses data from scientific publications, literature, official documents, archives, statistical compilations that are based on the actual material. Prospective method was applied for solving optimization problems evaluations relationships, interdependence and importance of the facts, evidence and reasoned theoretical generalizations justification logical conclusions and practical recommendations.

Results and Discussion. The main damaging factor is hyperglycemia, which through the activation of sorbitol pathway, protein kinase C and glycation of proteins leads to the development of oxidative stress, reduction of nitric oxide formation, activation of the pro-inflammatory pathway of NF-kB, which promotes accelerated progression of macroangiopathies, and also causes damage to the microvascular bed. Cerebral microangiopathy is part of the generalized vascular complications observed in diabetes, and more frequent adverse outcomes in these patients may be due to the systemic nature of vascular lesion and the negative impact of hyperglycemia on the course of the ischemic process. It is assumed that with diabetes, the damage to the inner layer of the vascular wall, the endothelium, is observed first. Endothelium normally provides a trophic and protective function in relation to other layers of the vascular wall. There is the endothelium that plays the main role in maintaining the vascular tone and hemostasis, in the development of remodeling and local inflammation (the development of pro and anti-inflammatory factors). Dysfunction of the endothelium and the formation of endothelial dysfunction in patients with insulin resistance leads to an increase in vascular reactivity. Imbalance of vasoconstrictors and vasodilators is one of the links in the pathogenesis of diabetic angiopathies, since trigger factors include inflammation processes with a change in smooth muscle function and excessive formation of pro-inflammatory cytokines.

Conclusions. The use of drugs with endothelioprotective properties can be considered as a primary line of effective prevention of vascular and neurological complications in patients with diabetes. The article substantiates the prospects of correction of endothelial dysfunction with an anti-inflammatory cytokine preparation, a receptor antagonist of interleukin-1.