Endothelial cell dysfunction, medial arterial calcification and osteoprotegerin in diabetes

Macrovascular complications such as cardiovascular disease and peripheral vascular disease are the leading cause of increased mortality and morbidity, respectively, in patients with diabetes mellitus. The aetiopathogenesis of macrovasculopathy in diabetes is multifactorial and differs in types 1 and 2 diabetes. Endothelial cell dysfunction is an early feature of diabetic vasculopathy and is associated with poor glycaemic control. Chronic hyperglycaemia may promote an adverse vascular milieu leading to early endothelial cell apoptosis, in the long run. The presence of apoptotic cells in the vascular lumen may trigger a cascade of reactions between the promoters and inhibitors of arterial calcification. Medial arterial calcification, a characteristic feature of diabetes, is an important predictor of cardiovascular disease and occurs independently of atherosclerosis. Medial arterial calcification may occur in the presence of normal serum calcium and phosphate levels. Osteoprotegerin is an important modulator of mineral metabolism and manifests its effects in the bone and arteries. It is hypothesised that osteoprotegerin is a key inhibitor of arterial calcification which is released by endothelial cells as a protective measure for survival in adverse conditions. It is a potential risk marker for early identification and monitoring of disturbed mineral metabolism and vasculopathy in diabetes.