Nonenzymatic glycosylation of proteins: clinical considerations

The recognition that free sugar condenses nonenzymatically with proteins and that this reaction is increased in the diabetic state with attendant hyperglycemia, has offered improved means for assessing diabetic control and has opened new avenues of investigation concerning the pathogenesis of diabetic complications. The principal contribution derived from studies of HbA1c is the demonstration that its measurement, when appropriately performed, can accurately reflect ambient blood glucose levels over an integrated period of time. Measurement of HbA1c does not substitute for standard glucose tolerance testing and, in the absence of overt hyperglycemia, does not adequately discriminate between diabetic and nondiabetic populations. A variety of methods for HbA1c determination are widely available, and the physician should understand factors that affect these methods, causing over- or underestimation of the amount of glycosylated hemoglobin. Although the exact pathophysiologic consequences of excess nonenzymatic glycosylation in diabetes are not defined, available evidence suggests that this process can alter structural and functional properties of involved problems. Such alterations may contribute to the development or progression of certain complications associated with chronic diabetes.