DIABETIC LATE COMPLICATIONS - WILL ALDOSE REDUCTASE INHIBITORS OR INHIBITORS OF ADVANCED GLYCOSYLATION ENDPRODUCT FORMATION HOLD PROMISE

Patients suffering from the severe complications associated with both insulin- (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM): n ephropathy, retinopathy, neuropathy, and atherosclerosis are still lar gely left without a prospect of an efficient treatment, This is the ca se even if it has been assumed for decades and now finally proved by t he results from the Diabetes Control and Complications Trial (DCCT) th at hyperglycemia is the single main cause of these complications. Impr oved glycemic control as a result of intensive insulin treatment has t he potential to reduce the incidence and progression of complications, but implementation and monitoring of improved glycemic control in all groups of IDDM and NIDDM patients in different communities will be di fficult and expensive. Results from the recently terminated DCCT have shown that even with intensive insulin treatment, there will still be a significant burden of complications on the diabetic population. It w ill, therefore, still be of immense importance for the long-term quali ty of life for the diabetic patient that additional possibilities are developed for prevention and intervention against diabetic complicatio ns. Almost two decades of research, animal model testing, and clinical trials have been conducted on various efficient aldose reductase inhi bitors. Now the concept of inhibition of formation of advanced glycosy lation endproducts on proteins and lipids resulting from extra- and in tracellular hyperglycemia is entering the scene as an alternative or p erhaps supplementary approach to reduce the occurrence of diabetic com plications. An overview of the results from these two fields of resear ch and associated drug-development programs will be presented along wi th thoughts on possible future developments.