Pathology and pathogenetic mechanisms of diabetic neuropathy: correlation with clinical signs and symptoms.

Drastic increase in diabetic patients poses serious problems in the care of neuropathy so that there needs to explore the pathogenesis and to establish the effective treatment. Recent clinical and basic studies revealed characteristic pathophysiology of diabetic neuropathy and some clue to the direction of the treatment. The pathology of diabetic neuropathy is characterized by progressive nerve fiber loss that gives rise to positive and negative clinical signs and symptoms such as pain, paresthesia and loss of sensation. The nerve fiber loss takes the form of pan-modal pattern with proximo-distal gradient. Endoneurial microangiopathic change is also a constant feature of peripheral nerve pathology and negatively correlates with nerve fiber density. The vascular change and distal nerve fiber loss of small caliber, in particular, at the site of epidermis, commence even in subjects with impaired glucose tolerance and precede loss of nerve fibers in the nerve trunk of lower extremities. Pathogenetic mechanisms underlying the progressive nerve fiber loss seem to be multifactorial, including polyol pathway, glycation, reactive oxygen species, and altered protein kinase C activity. Clinical trials based on this background confirmed that fundamental treatment is in fact beneficial for the prevention and halting of this intractable disorder.