Nonenzymatic glycation: a central mechanism in diabetic microvasculopathy?

Nonenzymatic glycation of proteins is one of several theories advanced in recent years to explain the pathogenesis of complications of diabetes. It is a condensation reaction between glucose and free amino groups, and the extent of glycation is largely dependent on the glucose concentration to which the protein is exposed and the biologic half-life of the involved protein. Because the lesions of diabetic microangiopathy involve basement membranes, many of the relevant studies have examined the consequences of excess glycation in collagen and other extracellular matrix proteins. Additionally, recent work indicates that glycated proteins, through a series of rearrangement reactions, give rise to abnormal cross links and complexes that are believed to alter structure-function properties and to have pathophysiologic importance. From these studies, a two-tiered scheme for the natural history of nonenzymatic glycation is proposed. This scheme is clinically relevant, particularly with respect to diabetic management programs.