Aldose reductase inhibition in the treatment of diabetic neuropathy: where are we in 2004?
Diabetic neuropathy is a major complication of poorly controlled diabetes mellitus. Aldose reductase, the first enzyme of the polyol pathway, is thought to play a role in initiating the metabolic damage to peripheral nerves during hyperglycemia. Aldose reductase inhibitors (ARIs) have been proposed to dampen the flux of glucose through the pathway during hyperglycemia; however, clinical trials in diabetic patients to demonstrate efficacy in the prevention or amelioration of diabetic neuropathy have failed thus far. Recent improved understanding of the pitfalls of past trials and some improved ARIs and clinical evaluation instruments show promise that success in the 20-plus year search for efficacious ARIs may soon be at hand.
Gabbay
Kenneth H
KH
Baylor College of Medicine, The Harry B. and Aileen B. Gordon Diabetes Research Center, 1102 Bates, Suite 830, MC 3-2353, Houston, TX 77030-2399, USA. kgabbay@bcm.tmc.edu
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D048289:Imidazolidines / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D048289:Imidazolidines; D000449:Aldehyde Reductase; C026411:sorbinil