Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7 +/- 0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p < 0.001), segmental demyelination (p < 0.01) and remyelination (p < 0.01) without axonal degeneration. Unassociated Schwann cell profile density (p < 0.04) and unmyelinated axon density (p < 0.001) were increased and axon diameter was decreased (p < 0.007). Endoneurial capillaries demonstrated basement membrane thickening (p < 0.006), endothelial cell hyperplasia (p < 0.004) and a reduction in luminal area (p < 0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.
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Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USAUniv Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
Hur, Junguk
Sullivan, Kelli A.
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Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Med Educ, Ann Arbor, MI 48109 USAUniv Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
Sullivan, Kelli A.
Callaghan, Brian C.
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Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USAUniv Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
Callaghan, Brian C.
Pop-Busui, Rodica
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Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USAUniv Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
Pop-Busui, Rodica
Feldman, Eva L.
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Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USAUniv Michigan, Dept Neurol, Ann Arbor, MI 48109 USA