What are contributing factors to the development of diabetic neuropathy?

Updated: Jan 17, 2020
  • Author: Dianna Quan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Problems that are a consequence of or co-contributors to these disturbed biochemical processes include altered gene expression with altered cellular phenotypes, changes in cell physiology relating to endoskeletal structure or cellular transport, reduction in neurotrophins, and nerve ischemia. [21] Clinical trials of the best-studied neurotrophin, human recombinant nerve growth factor, were disappointing. With future refinements, however, pharmacologic intervention targeting one or more of these mechanisms may prove successful.

In the case of focal or asymmetrical diabetic neuropathy syndromes, vascular injury or autoimmunity may play more important roles. [22]

A cross-sectional, case-control study by Gastoł et al indicated that in patients with type 1 diabetes mellitus (DM), epigenetic factors are involved in the development of autonomic neuropathy. T1DM patients with autonomic neuropathy showed differences in gene methylation compared with T1DM patients without neuropathy. For example, in the NINJ2 gene, which is involved in nerve regeneration, patients with autonomic neuropathy had significantly greater methylation in the first axon than did the other patients with type 1. In addition, two genes involved in nerve functionality, BRSK2 and CLDN4, showed decreased methylation (in the region of the first intron of BRSK2 and the 5’UTR regions of CLDN4) in the patients with neuropathy. [23]

A study by Groener et al of sciatic nerve lesions in diabetic polyneuropathy indicated that lesion load positively correlates with the duration of diabetes, attaining clinical relevance “once a critical amount of nerve fascicles is affected.” [24]

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