THE POLYOL PATHWAY - A CULPRIT IN DIABETIC NEUROPATHY

The development of diabetic neuropathy is strongly linked to chronic h yperglycemia. While numerous biochemical mechanism(s) are suspected of mediating this linkage, substantial evidence points an incriminating finger at the polyol pathway. In particular, structurally distinct inh ibitors of aldose reductase (ARIs) prevent, retard, and sometimes reve rse, functional and structural nerve abnormalities in animal models of diabetic neuropathy. Early trials of ARIs in human diabetics have sho wn ''small'' positive effects on nerve function and structure, but hav e been disappointing to some because of both overly optimistic therape utic expectations and deficiencies in the pharmacodynamic or toleratio n profiles of the agents tested. Recently, strong new evidence has eme rged that better defines the impact of intensified glycemic control on diabetic neuropathy and provides more realistic therapeutic expectati ons for ARI therapy. In this context, clinical results with current AR Is offer substantial encouragement for the therapeutic potential of AR Is to treat, slow and prevent diabetic neuropathy.