Pathologic alterations in the diabetic neuropathies of humans: a review

J Neuropathol Exp Neurol. 1996 Dec;55(12):1181-93. doi: 10.1097/00005072-199612000-00001.


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. Repetitive shear forces, anatomic factors, and excessive stiffness of connective tissues may cause these mononeuropathies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Atrophy
  • Axons / pathology
  • Diabetic Angiopathies / complications
  • Diabetic Neuropathies / pathology*
  • Humans
  • Hypertrophy
  • Motor Neurons / pathology
  • Nerve Degeneration
  • Nerve Fibers / pathology
  • Nerve Regeneration
  • Neural Conduction
  • Peripheral Nerves / blood supply
  • Schwann Cells / metabolism
  • Spinal Nerves / pathology