Glucose-induced oxidative stress and programmed cell death in diabetic neuropathy

The Diabetes Control and Complications Trial (DCCT) established the importa nce of hyperglyemia and other consequences of insulin deficiency in the pat hogenesis of diabetic neuropathy, but the precise mechanisms by which metab olic alterations produce peripheral nerve fiber damage and loss remain uncl ear. Emerging data from human and animal studies suggest that glucose-deriv ed oxidative stress may play a central role, linking together many of the o ther currently invoked pathogenetic mechanisms such as the aldose reductase and glycation pathways, vascular dysfunction, and impaired neurotrophic su pport. These relationships suggest combinations of pharmacological interven tions that may synergistically protect the peripheral nervous system (PNS) against the metabolic derangements of diabetes mellitus. (C) 1999 Elsevier Science B.V. All rights reserved.