New therapies for the chronic complications of older diabetic patients.

Recently, four biochemical mechanisms have been implicated in the pathogenesis of certain late complications of diabetes mellitus. All of these mechanisms (altered polyol pathway activity, disrupted myo-inositol metabolism, increased vascular permeability, and increased nonenzymatic glycosylation of proteins) are activated by exposure of tissues to hyperglycemia. There is evidence to suggest that the development of retinopathy, nephropathy, and neuropathy is directly related to the level of glycemia in patients with diabetes mellitus. Whether strict glycemic control will prevent or reverse diabetic complications is the subject of the Diabetes Control and Complications Trial. Until the results of that study are reported, and until euglycemia can be achieved in all diabetic patients, the search will continue for other pharmacologic agents that might prevent the development of complications. Therapies that are currently under investigation include administration of aldose reductase inhibitors and supplementation of dietary myo-inositol. It is too early to conclude whether such therapies will prove useful in the prevention or reversal of diabetic complications.