Negative consequences of glycation.

The Diabetes Control and Complications Trial (DCCT) established unequivocally that the effects of inadequate insulin action (as monitored by the level of hyperglycemia) are associated with the incidence and progression of diabetic retinopathy, nephropathy, and neuropathy. How does hyperglycemia induce the functional and morphologic changes that characterize diabetic complications? Increasing evidence points to a major role for sugar-derived advanced glycation end products (AGEs), which form inside and outside cells as a function of glucose concentration. Recent work in this area supports a central role for reactive oxygen species (ROS) in both the formation of AGEs, and in AGE-induced pathologic alterations in gene expression. Inhibition of ROS may also be centrally important in the action of drugs that prevent complications in diabetic animal models.