Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy
Clinical, electrophysiological and ultrastructural morphometric observations were made in 5 diabetic non-neuropathic patients, 5 diabetic patients with mild neuropathy and 11 diabetic patients with severe neuropathy. Capillary abnormalities were assessed in simultaneous nerve, muscle and skin biopsies and compared with results from 6 age-matched, non-diabetic control subjects. Nerve capillaries demonstrated markedly greater pathology than skin and muscle capillaries. Endoneurial capillary density was significantly reduced in severely neuropathic diabetic patients (p less than 0.01) when compared with control subjects. Capillary basement membrane (p less than 0.002), endothelial cell (p less than 0.003) and total diffusion barrier (endothelial cell, pericyte, basement membrane) (p less than 0.001) thickness were significantly increased, and oxygen diffusing capacity was significantly reduced (p less than 0.001) in the nerves of patients with severe diabetic neuropathy when compared to control subjects. Endothelial cell profile number and luminal perimeter were significantly increased in asymptomatic (p less than 0.01), (p less than 0.05) and severely neuropathic (p less than 0.001), (p less than 0.05) diabetic patients respectively. However, endothelial cell outer perimeter, a measure of capillary size, showed no significant increase in diabetic patients when compared with control subjects. An association was observed between neurophysiological and neuropathological measures of neuropathic severity. There was no significant correlation between the duration of diabetes and HbA1 levels with capillary pathology or with neuropathic severity. Very few abnormalities of muscle and skin correlated with neuropathic severity. However, all measures of nerve capillary pathology correlated significantly with neurophysiological and neuropathological measures of neuropathic severity.