Endothelial dysfunction and pathogenesis of diabetic angiopathy.

OBJECTIVE AND METHODS To review, from the clinical perspective, the contribution of dysfunction of the vascular endothelium to the pathogenesis of diabetic micro- and macroangiopathy. RESULTS Available data indicate that endothelial dysfunction in diabetes complicated by micro- or macroalbuminuria (renal microangiopathy) is generalised. The close linkage between microalbuminuria and endothelial dysfunction is an attractive explanation for the fact that microalbuminuria is a risk marker for atherosclerotic cardiovascular disease in diabetes. Endothelial dysfunction precedes the occurrence of even early diabetic microangiopathy. However, it is not clear whether endothelial dysfunction is a feature of the diabetic state per se or whether additional factors are required to induce endothelial dysfunction given the presence of diabetes. Convincing data from animal and in vitro models exist to indicate that endothelial dysfunction in diabetes may be related to hyperglycaemic pseudohypoxia, activation of protein kinase C, increased expression of transforming growth factor-beta and vascular endothelial growth factor, non-enzymatic glycation, oxidative stress, activation of the coagulation cascade, increased expression of tumour necrosis factor-alpha, and high levels of insulin and insulin precursor molecules. However, the importance of these proposed mechanisms have not yet been extensively assessed in diabetes in man. CONCLUSIONS Endothelial dysfunction plays a key role in the pathogenesis of diabetic angiopathy in man. The biochemical basis of endothelial dysfunction in diabetic man, however, has yet to be fully elucidated.