Diabetes. Reasons and development mechanisms

In 1994, 110.4 million patients with diabetes were registered in the world, by 2000 their number had almost doubled, amounting to about 175 million, by 2025 there would be about 300 million patients with diabetes in the world (Fujimoto WY). The socio-economic significance of the problem is difficult to overestimate. Currently, about 200 million patients with diabetes live on Earth, however, given the existence of a fairly large number of undiagnosed cases of the disease, the exact number is obviously significantly higher. Diabetes mellitus and its complications occupy one of the first places among the causes of ipvalidization and mortality, significantly reduce the quality of life. The costs of medical care for this category of patients make up a significant part of the health budget in all developed countries of the world. In Russia, 3-6% of the population suffers from diabetes, in the age group over 60 years old – up to 10%, and over 65 years old – up to 16% (Balabolkin MI). Diabetes mellitus is a heterogeneous group of diseases that are different in origin, pathogenesis, clinical course and treatment approaches. Despite the variety of clinical forms of diabetes, all of them are characterized by impaired glucose utilization with the development of hyperglycemia, cascading metabolic disorders and multiple organ disorders with damage to the nervous and vascular systems, kidneys and eyes. The similarity of different forms of diabetes is explained by the presence of hyperglycemia and the most striking clinical manifestations associated with it: dry mouth, polyphagia, polydipsia (thirst), polyuria, asthenia and increased fatigue, skin itching, etc. However, the mechanisms of formation of hyperglycemia are significantly different, which leads to features of the development of both the disease itself and its complications, including damage to the nervous system. The basis of disorders of carbohydrate metabolism is the absolute or relative deficiency of insulin. The secretion of insulin occurs in the islet (3-cells of the pancreas (pancreas) and is regulated by glucose by the feedback mechanism. Glucose produced by aerobic glycolysis of hexose and cAMP have a direct effect on the transcription of the gene encoding insulin (located on the short arm of the 11th chromosome ), activating it. As a result, the amount of matrix RNA increases correspondingly to an increase in the need for insulin. Translation of matrix RNA leads to the formation of proinsulin, which accumulates in secretory granules, where it it is converted to insulin and C-peptide, which are released in equimolar concentrations through exocytosis upon activation of P cells by various factors, including hormones, metabolites, and neurogenic influences. Glucose utilization under the influence of insulin occurs in the so-called insulin-dependent tissues – liver, muscle, fat tissue by means of special proteins of glycoproteins – glucose transporters through lipophilic membranes of cells with species and tissue specificity, i.e., glucose transfer in various tissues it is found by specific hierocarrier proteins. Insulin is not required for glucose consumption in non-insulin-dependent tissues (central nervous system, blood cells). The process of glucose entering the cell of an insulin-dependent tissue begins with the binding of the insulin molecule to a specific receptor on the surface of the cell membrane. The formation of the insulin receptor complex, in turn, is the initial link in the chain of intracellular processes leading to the activation of the tyrosine kinase enzyme, increased phosphorylation and migration of glucose transporters to the inner surface of the cell membrane, as a result of which glucose uptake into the cell increases by 20-40 times. It is at this level that disorders occur that lead to the phenomenon of insulin resistance – a decrease in the sensitivity of peripheral insulin receptors (impaired glucose tolerance) – a key factor in the pathogenesis of NIDDM. So, under normal conditions, tyrosine kinase activity increases in parallel with an increase in plasma glucose concentrationblood, while in patients with type 2 diabetes, its activity decreases by 50% or more. In patients with type 2 diabetes, insulin binding due to a decrease in the number of membrane receptors is reduced by 30% (Ametov A.S. et al.), Which inevitably leads to a decrease in glucose uptake into peripheral tissues and the development of hyperglycemia. Thus, hyperglycemia can occur due to both insufficient insulin secretion and an inadequate reaction of peripheral tissues to plasma glucose. Regardless of the nature of diabetes and its initiating factors, as the disease develops, a progressive decrease in the number of functioning b-cells and the development of absolute insulin deficiency develops sharply or gradually.

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