Diabetes mellitus is a major cause of peripheral neurophathy, commonly manifexted as distal symmetrical polyneuropathy.
Although chronic hyperglycaemia is almost certainly involved, it is not known whether the promary pa-thology is metabolic, microvascular or interaction between the two.
The heterogeneity of diabetic neuropathy with involvment of large, myelinated fibres, as will as, small, thinly, or nonmyelinated fibers, suggests multible fzctors in pathogenesis.
In this review we discuss the biochemistry and pathophysiology of hyperglycemia and the main theories of pathogenesis of diabetic neuropathy.
Vascular role in pathogenesis of diabetic neuropathy has been discussed since 1893. Studies in human and animal models have shown reduced nerve perfusion and endoneurial hypoxia. Investigations on biopsy material from pathients with diabetic neuropathy show graded structural changes in nerve microvasculature including basement membrane thickening, pericyte degeneration and endothelial cell hyperplasia.
However, In many experimental and theoretical researches, the greatest attention has focussed on metabolic disorders like: advanced glycation of structural proteins and accumulation of advanced GE; the activation of polyol pathway and accumulation of sorbitol, myo-inositol depletion and decreased protein kinasse C activity; increasing the formation of reactive oxygen spcies that causes serious damage to neuronal membranes.
Followers of the metabolic theory consider vaso defects to be postprimary as the result of metabolic dis-order.
Despite considerable research, we still do not have a comprehensive explanation for the pathogenesis of diabetic neuropathy.
The review is based on the relevand literature published in the English language during the period 1990–2009.