BACKGROUND AND METHODS. The pathophysiologic features of diabetic neuropathy, a common and disabling long-term complication of diabetes mellitus, are poorly understood. We studied five patients, 22 to 34 years old, in whom an uncommonly severe symmetric polyneuropathy developed soon after the onset of insulin-dependent diabetes. Their autonomic function and nerve conduction were studied, and sural-nerve biopsy specimens were examined by light and electron microscopy. Other causes of neuropathy were carefully excluded. RESULTS. Four patients had autonomic dysfunction with postural hypotension, fainting, diarrhea, and Argyll Robertson pupils and peripheral neuropathy with loss of sensation of pain and changes in temperature that followed a pattern suggestive of a length-dependent degeneration of nerve fibers. In contrast, the fifth patient had muscle weakness and atrophy of limb extremities, with "glove and stocking" sensory loss, but little autonomic dysfunction. In the biopsy specimens of sural nerves, the mean (+/- SD) density of myelinated fibers was reduced to 20 +/- 14 percent of that measured in five control patients, and the density of unmyelinated fibers was reduced to 6 +/- 4 percent of that in the controls. Regenerating fibers accounted for 38 +/- 11 percent of the myelinated axons. Abnormalities of the myelin sheath affected 33 +/- 21 percent of the isolated fibers, and axonal degeneration 11 +/- 8 percent. Dying-back fibers, a characteristic of the centripetal degeneration of peripheral axons, were also identified. The dying-back process progressed at the rate of a few hundred micrometers per day. CONCLUSIONS. Early-onset symptomatic polyneuropathy in patients with diabetes mellitus is characterized by the loss of both myelinated and unmyelinated nerve fibers. Spontaneous axonal regeneration is remarkably frequent, even when neuropathy is severe.
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Service de Neurologie, Hopital de Bicetre (Universite Paris XI), France.
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