Impact of hyperglycemia on endothelial dysfunction and development of late complications in diabetes mellitus

According to the WHO definition, atherosclerosis is a chronic, systemic, degenerative, inflammatory, proliferative disease, developing primarily in the large and medium sized arteries with the preferred localization at the arterial bifurcations. Atherosclerosis is an inevitable process. An intact endothelium is characterized by thromboresistance and vasodilatation. However, blood vessels in diabetics, compared to healthy persons of the same age are appear twelve years older, due to the following reasons: hyperglycemia, hyperinsulinemia and hyperleptinemia in the obese, hyper- and dyslipidemia, arterial hypertension, elevated fibrinogen and uric acid levels. Hyperglycemia, causes glycation of proteins, initially reversible, but eventually Amadori products are transformed into the advanced glycation end products (AGEs), representing irreversible, metabolically active bonds. In diabetics, this process involves extensive generation of free radicals. Level of their production depends on the glycation level, i.e. hyperglycemia. Free radicals are capable of further independent existence, and are potent oxidants. All this contributes to the development of hyper- and dyslipoproteinemia, arterial hypertension and subsequent endothelial dysfunction coupled with atherosclerosis with its macro- and microvascular complications of the ocular fundus, heart, peripheral arteries and nerves, as well as in kidneys in type 1 or 2 diabetes mellitus sufferers. Efficient metabolic control of diabetics, implying preprandial normoglycemia and postprandial hyperglycemia bellow 8 mmol/l, enabled by life style changes, an appropriate choice and dose of peroral antidiabetic drags, and timely introduction of insulin therapy, will undoubtedly prevent or delay the occurrence of the endothelial dysfunction, atherosclerosis and its aftereffects. .