Pathologic alterations in the diabetic neuropathies of humans: A review

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264 Scopus citations


Pathologic study of nerve tissue is especially useful for the recognition of interstitial events such as inflammation or vascular alterations that cannot be inferred from clinical or electrophysiologic findings and may provide insight into an underlying mechanism or cause. Considerable variation in the natural history and pathologic alterations among diabetic neuropathies suggests that they are heterogeneous. For diabetic polyneuropathy, two mechanisms need to be considered. The first assumes that hyperglycemia induces metabolic derangements that directly affect Schwann cells (or myelin), nodes of Ranvier, or axons. The second assumes that hyperglycemia and metabolic derangement affect the structure and function of endoneurial microvessels, which then induce fiber changes by altering the blood nerve barrier, inducing hypoxia or ischemia, or by unknown mechanisms. In proximal diabetic neuropathy, there is increasing evidence that the characteristic lesion is an inflammatory (immune) vasculitis that induces ischemic nerve fiber degeneration. Truncal radiculopathy may be due to an inflammatory polyganglionopathy. In cranial nerve III neuropathy, the monophasic course and the pathologic alterations of ischemia suggest that localized vasculitis should be excluded in future cases. Many upper limb mononeuropathies in diabetes mellitus are from carpal tunnel syndrome or cubital tunnel syndrome. Repetitive shear forces, anatomic factors, and excessive stiffness of connective tissues may cause these mononeuropathies.

Original languageEnglish (US)
Pages (from-to)1181-1193
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Issue number12
StatePublished - Dec 1996


  • Carpal tunnel syndrome
  • Cubital tunnel syndrome
  • Diabetic neuropathy
  • Diabetic oculomotor neuropathy
  • Diabetic polyneuropathy
  • Pathology
  • Proximal diabetic neuropathy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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