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  • Review Article
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Diabetic neuropathy: cellular mechanisms as therapeutic targets

Nature Reviews Neurology volume 7, pages 573–583 (2011)Cite this article

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Abstract

In patients with diabetes, nerve injury is a common complication that leads to chronic pain, numbness and substantial loss of quality of life. Good glycemic control can decrease the incidence of diabetic neuropathy, but more than half of all patients with diabetes still develop this complication. There is no approved treatment to prevent or halt diabetic neuropathy, and only symptomatic pain therapies, with variable efficacy, are available. New insights into the mechanisms leading to the development of diabetic neuropathy continue to point to systemic and cellular imbalances in metabolites of glucose and lipids. In the PNS, sensory neurons, Schwann cells and the microvascular endothelium are vulnerable to oxidative and inflammatory stress in the presence of these altered metabolic substrates. This Review discusses the emerging cellular mechanisms that are activated in the diabetic milieu of hyperglycemia, dyslipidemia and impaired insulin signaling. We highlight the pathways to cellular injury, thereby identifying promising therapeutic targets, including mitochondrial function and inflammation.

Key Points

  • Multiple metabolic imbalances underlie the development of diabetic neuropathy

  • Hyperglycemia, dyslipidemia and cardiovascular dysfunction are each independent risk factors for neuropathy

  • Targeting risk factors as well as cellular oxidative stress and inflammation will be important in future treatment approaches

  • Injury to neurons, Schwann cells and microvascular endothelial cells in the diabetic milieu contributes to the pathogenesis of neuropathy

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Figure 1: Hyperglycemia and hyperlipidemia activate multiple injury mechanisms in sensory neurons.
Figure 2: Proposed algorithm for treating pain in diabetic neuropathy.

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  1. Department of Neurology, University of Michigan, 5371 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, 48109-0588, MI, USA

    Andrea M. Vincent, Brian C. Callaghan, Andrea L. Smith & Eva L. Feldman

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A. M. Vincent researched data for the article. All authors contributed to discussions of the content, writing of the article, and review and/or editing of the manuscript before submission.

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Vincent, A., Callaghan, B., Smith, A. et al. Diabetic neuropathy: cellular mechanisms as therapeutic targets. Nat Rev Neurol 7, 573–583 (2011). https://doi.org/10.1038/nrneurol.2011.137

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