Nerve lipid abnormalities in human diabetic neuropathy: A correlative study

Authors

  • Dr Mark J. Brown MD,

    Corresponding author
    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Eunice Kennedy Shriver Center, Waltham, MA
    3. Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA
    • Brown, Department of Neurology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104
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  • Masao Iwamori BA,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Eunice Kennedy Shriver Center, Waltham, MA
    3. Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA
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  • Yasuo Kishimoto PhD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Eunice Kennedy Shriver Center, Waltham, MA
    3. Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA
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  • Basil Rapoport MB,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Eunice Kennedy Shriver Center, Waltham, MA
    3. Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA
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  • Hugo W. Moser MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Eunice Kennedy Shriver Center, Waltham, MA
    3. Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA
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  • Arthur K. Asbury MD

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Eunice Kennedy Shriver Center, Waltham, MA
    3. Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA
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Abstract

To study endoneurial lipid composition in human diabetic neuropathy, we biopsied sural nerves from 3 middleaged men with adult-onset diabetes mellitus. Magnitude of electrophysiological abnormalities and myelinated fiber loss paralleled the clinical severity of neuropathy in all cases. Cholesterol ester concentration was elevated to about 800% of normal in diabetic nerves. Reduction in total endoneurial lipid concentration correlated best with decrease in myelin volume as calculated from measured fiber diameters. Cholesterol, cerebroside, and most phospholipids were reduced in keeping with the severity of fiber loss in each nerve. The phosphatidylinositol-phosphatidylserine fraction was most reduced in the least affected nerves. Cerebroside nonhydroxy fatty acids in diabetic nerves were of shorter chain length and more saturated than normal. It is not yet clear whether the abnormalities of phosphatidylinositol-phosphatidylserine and cerebroside fatty acids are of pathogenetic importance or whether these changes may be the nonspecific consequence of axonal degeneration.

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