The heterogeneity of diabetic neuropathy.

Diabetic neuropathy and its underlying pathogenesis are reviewed. It has been documented for some time that diabetic neuropathy differs in both human and experimental type 1 versus type 2 diabetes. Such differences are accounted for by impaired insulin action and signal transduction in type 1 diabetes, whereas hyperglycemia per se contributes equally to neuropathy in the two types of diabetes. Such differences in basic initiating factors and pathogenesis translate into differences in the functional and structural expressions of neuropathy in type 1 and type 2 diabetes. Type 1 neuropathy shows a more rapid progression with more severe functional and structural changes. Several experimental mono-therapies have been tested over the last decades which unfortunately have not been efficacious. Therefore discrepancies in underlying pathogenetic mechanisms in the two types of diabetic neuropathy will have to be taken into account in the design of future therapies, which should target several key pathogenetic mechanisms. Therapies that meet these criteria include replacement of acetyl-L-carnitine and replenishment of C-peptide in type 1 diabetic neuropathy.