Glycemic control and the initiation and progression of the complications of diabetes mellitus

The effect of improved glycemic control on the prevention or reversal of diabetic nephropathy has been optimally shown by the reduced incidence of albuminuria (accompanied by an increased risk of hypoglycemia) in the Diabetes Control and Complications Trial (DCCT). The earliest detection of the risk or of the presence of diabetic nephropathy continues to be elevated (and confirmed) levels of albuminuria. However, micro- and macroalbuminuria are frequently associated with increased glycated hemoglobin values, complicating attempts to separate the influence of glycemia from an inherent susceptibility for diabetic nephropathy. In the type 1 diabetic patient levels of c-peptide (co-secreted with insulin by the islets of Langerhans) in plasma reflect sustained islet function. C-peptide may be measured in plasma for as long as a decade after the clinical diagnosis of diabetes mellitus, and its presence may be prolonged with better management of diabetes. The consequent improved glycemic control afforded by sustained islet function will reduce the incidence of the retinopathic and nephropathic complications, uniquely accompanied by a lower risk of hypoglycemia. Optimal diabetic management (that is, normal glycemic indices for all diabetic subjects) remains the goal of diabetic therapy. However, failure to normalize glycemic control may remain a reality of contemporary diabetic management. Thus, renal function assays or genetic protocols (each proposed for the earliest detection of diabetic nephropathy) will need to identify individuals at risk against a broadly variable background of glycated hemoglobin levels.