Oxidative stress and cardiovascular complications in diabetes: isoprostanes as new markers on an old paradigm

Long-term vascular complications still represent the main cause of morbidit y and mortality in diabetic patients. Although randomized long-term clinica l studies comparing the effects of conventional and intensive therapy have demonstrated a clear link between hyperglycemia and the development of comp lications of diabetes, they have not defined the mechanism through which ex cess glucose results in tissue damage. Evidence has accumulated indicating that oxidative stress may play a key role in the etiology of diabetic compl ications. Isoprostanes are emerging as a new class of biologically active p roducts of arachidonic acid metabolism of potential relevance to human Vasc ular disease. Their formation in vivo seems to reflect primarily, if not ex clusively, a nonenzymatic process of Lipid peroxidation. Enhanced urinary e xcretion of 8-iso-PGF(2 alpha) has been described in association with both type 1 and type 2 diabetes mellitus, and correlates with impaired glycemic control. Besides providing a likely noninvasive index of lipid peroxidation in this setting, measurements of specific F-2 isoprostanes in urine may pr ovide a sensitive biochemical end point for dose-finding studies of natural and synthetic inhibitors of lipid peroxidation. Although the biological ef fects of 8-iso-PGF(2 alpha) in vitro suggest that it and other isoeicosanoi ds may modulate the functional consequences of lipid peroxidation in diabet es, evidence that this is likely in vivo remains inadequate at this time. ( C) 2000 Elsevier Science B.V. All rights reserved.