Pathology and pathogenesis of diabetic neuropathy

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3 Citations (Scopus)


Two coherent features underpin the pathology of human diabetic neuropathy: nerve fibers degenerate and blood vessels supplying them are grossly diseased. Unless one naively assumes that the blood vessels play no role in the maintenance of normal nerve function, the failure to link microangiopathy with neuropathy may well be perceived as a major failing to adequately address the pathogenesis of human diabetic neuropathy. Yet, until the last 10 years, the role of vascular factors in the pathogenesis of diabetic neuropathy was denied or seriously questioned. However, the recent explosion of data from animal models, supported by in vivo and pathological studies in diabetic patients, provides incontrovertible evidence that microangiopathy plays a crucial role in the pathogenesis of nerve damage. Furthermore, the development of a significant microangiopathy may form the critical point, which determines whether or not nerve fibers repair themselves or proceed to total degeneration and hence clinically relevant neuropathy. While hyperglycemia and many of its secondary transducers, including the polyol pathway, glycation, and oxidative stress, may contribute to peripheral nerve degeneration, and neurotrophins to regeneration, the key control mechanism lies in the vasculature. Thus, therapeutic intervention with a range of vasoactive drugs improves nerve function in animal models. Promising results in diabetic patients have also been achieved using a range of therapies, including large-vessel revascularization, ACE inhibitors, γ-linoleic acid, and α-lipoic acid. We await the results of large clinical trials involving therapies acting via the vascular axis to truly test the clinical relevance of the vascular hypothesis and thus aid in the development of a meaningful treatment for human diabetic neuropathy.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalDiabetes Reviews
Issue number4
Publication statusPublished - 1999
Externally publishedYes


ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

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