Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy.
Altered sorbitol and myo-inositol metabolism, (Na,K)-ATPase function, electrochemical sodium gradients, axonal swelling, and distortion and disruption of the node of Ranvier ("axo-glial dysjunction") directly implicate hyperglycemia in the pathogenesis of neuropathy in diabetic rats, but the relevance of this sequence to clinical neuropathy in heterogeneous groups of diabetic patients remains to be established. Fascicular sural nerve morphometry in 11 patients with neuropathy complicating insulin-dependent diabetes revealed a pattern of interrelated structural changes strikingly similar to that of the diabetic rat when compared to age-matched controls. 17 older non-insulin-dependent diabetic patients with comparable duration and severity of hyperglycemia and severity of neuropathy, displayed similar nerve fiber loss, paranodal demyelination, paranodal remyelination and segmental demyelination compared to age-matched controls, but axo-glial dysjunction was replaced by Wallerian degeneration as the primary manifestation of fiber damage, and fiber loss occurred in a spatial pattern consistent with an ischemic component. The mechanistic model developed from the diabetic rat does indeed appear to apply to human diabetic neuropathy, but superimposed hormonal, metabolic, vascular, and/or age-related effects alter the morphologic expression of the neuropathy in non-insulin dependent diabetes.
Sima
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AA
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Nathaniel
V
V
Bril
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V
McEwen
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Greene
D A
DA
D000367:Age Factors; D001369:Axons / Q000473:pathology; D003711:Demyelinating Diseases / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology*; D006801:Humans; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000473:pathology; D009431:Neural Conduction; D009457:Neuroglia / Q000473:pathology; D011901:Ranvier's Nodes / Q000473:pathology*