Microangiopathy in human diabetic neuropathy

Summary Morphological change of endoneurial and perineurial vessels accompanied severe loss of myelinated axons in peripheral nerves of each of 17 patients with diabetic neuropathy. Vascular mural thickening averaged 18.9±9.9 m² in diabetic capillaries (n=11) vs. 6.9±4.1 m² in controls (n=7). Electron microscopy revealed vigorous endothelial proliferation as well as thickening and reduplication of basal lamina in each instance. Particular attention was paid to vessels which penetrate the perineurium en route to the endoneurial intertitium, since they provide a major portion of the endoneurial blood supply. Luminal narrowing and mural thickening of these vessels was compounded by basal laminar thickening of the perineurium. Fenestrated endoneurial capillary endothelium was noted in one case. Both demyelination and axonal degeneration were observed with intra-axonal glycogen accumulation in some axons. Morphometric analysis revealed extensive myelinated nerve fiber loss in diabetic nerves. These morphological findings emphasize the impact of diabetic microangiopathy on specialized endothelium and suggest that local anatomic factors in the perineurial sheath render the nerve vulnerable to chronic ischemia.Supported in part by the National Institute for Communicative Disorders and Stroke NS-14162 and by the Veterans Administration Research Service