Role of advanced glycation end products (AGEs) in thrombogenic abnormalities in diabetes.

Accelerated atherosclerosis and microvascular complications are perhaps the leading cause of coronary heart disease, blindness and renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Several thrombogenic abnormalities have been shown to play a central role in the pathogenesis of these devastating complications. However, the molecular mechanism for thrombogenic diathesis in diabetes is not fully elucidated. A recent clinical study, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that the reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persist for at least several years, despite increasing hyperglycemia. Further, intensive therapy during the DCCT resulted in decreased progression of carotid intima-media thickness six years after the end of the trial as well. These clinical studies strongly suggest that so-called 'hyperglycemic memory' causes chronic abnormalities in diabetic vessels that are not easily reversed, even by subsequent, relatively good control of blood glucose. Among various biochemical pathways activated under diabetes, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. In this review, we discuss the role of AGEs in thrombogenic abnormalities in diabetes.