Diabetic vascular disease: Cellular and molecular approach

Abstract

The term diabetes mellitus refers to a state of chronic hyperglycemia due to absolute or relative deficiency of insulin secretion with disordered metabolism of carbohydrates, lipids and proteins. More than 35 million people in Europe are diagnosed with diabetes. In 2030, it is expected that this figure will rise to 43 million. According to the International diabetes federation (IDF), more than 415 million people around the world are diagnosed with diabetes, and in 2040, IDF estimates that 642 million people will have diabetes. The metabolic syndrome (cluster of more or less related metabolic and cardiovascular derangements including visceral obesity, insulin resistance, dyslipidemia, hypertension and glucose intolerance) significantly contributes to development of diabetes mellitus type 2. This syndrome is characterized by a primary cellular defect in insulin action due to disorders in insulin signal transduction (insulin is unable to achieve its biological effects adequately). Under these conditions, insulin resistance in combination with hyperinsulinemia causes numerous metabolic and cardiovascular disorders that are a leading cause of morbidity and mortality worldwide. Thus, 65% of people with diabetes around the world die from cardiovascular disease. Besides, this serious condition is manifested by development of chronic angiopathic complications, such as micro-angiopathy and atherosclerosis. Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Pathogenesis of accelerated atherosclerosis in people with diabetes is not fully understood. Endothelial dysfunction is recognized as the crucial step in atherogenesis. A lot of studies have confirmed the role of dyslipidemia, hyperglycemia, oxidative stress and various mediators of inflammation in initial proatherogenic processes. After foam cell formation, mediators of inflammation initiate a series of intracellular events that include the induction of inflammatory cytokines. Thus, a vicious circle of inflammation, modification of lipoproteins and further inflammation can be maintained in the artery. Inflammatory process, matrix-degrading metalloproteinases activity, platelets aggregation and smooth muscle cells proliferation play a central role in development of fibrotic plaque. It has been shown that inflammation is closely related to the development of atherosclerotic plaque rupture. Having in mind an increase in diabetic vascular disease prevalence in future, it is necessary to take preventive actions to decrease the risk factors (inappropriate diet rich in carbohydrates and saturated fatty acids, smoking, sedentary lifestyle and physical inactivity). Apart from lifestyle changes, the usage of hypocaloric diet and increasing the level of physical activity, in patients with diabetic vascular disease, it is necessary to apply psychoeducation, as well as appropriate cognitive behavioral and medical therapy. However, although various studies related to this health problem have been carried out, scientists are still far from a complete understanding of the cellular and molecular basis of this problem.