Glycochelates and the etiology of diabetic peripheral neuropathy

People with diabetes are prone to develop peripheral vascular and nerve abn ormalities which, in extreme cases, can lead to limb amputations. Although numerous theories have been advanced for these complications, no firm expla nation is yet available. Recently, evidence has appeared suggesting that th ese vascular and nerve abnormalities may involve transition metals; adminis tration of chelators such as desferrioxamine has been shown to prevent or a ctually reverse slowed peripheral nerve conduction and neuronal blood flow, as well as impaired endothelium-dependent arterial relaxation. Here, we ar gue that (i) the heavily glycated proteins known to accumulate in people wi th diabetes gain an increased affinity for transition metals such as iron a nd copper, (ii) as a result, proteins such as elastin and collagen within t he arterial wall-which are known to be particularly heavily glycosylated in diabetes-may accumulate bound metal, especially copper, (iii) the bound me tal causes the catalytic destruction of endothelium derived relaxing factor (nitric oxide or a derivative thereon, thereby engendering a state of chro nic vasoconstriction. The resulting impairment of blood flow to peripheral nerves restricts the delivery of oxygen and nutrients and, in extremis, ner ve death eventuates. If this hypothesis is proved correct, there are import ant implications for the development of novel pharmaceuticals for the treat ment of diabetic peripheral neuropathy. (C) 2000 Elsevier Science Inc.