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  • Primer
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Diabetic neuropathy

Nature Reviews Disease Primers volume 5, Article number: 41 (2019) Cite this article

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Abstract

The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy, of which distal symmetric polyneuropathy (for the purpose of this Primer, referred to as diabetic neuropathy) is very common. Diabetic neuropathy is a loss of sensory function beginning distally in the lower extremities that is also characterized by pain and substantial morbidity. Over time, at least 50% of individuals with diabetes develop diabetic neuropathy. Glucose control effectively halts the progression of diabetic neuropathy in patients with type 1 diabetes mellitus, but the effects are more modest in those with type 2 diabetes mellitus. These findings have led to new efforts to understand the aetiology of diabetic neuropathy, along with new 2017 recommendations on approaches to prevent and treat this disorder that are specific for each type of diabetes. In parallel, new guidelines for the treatment of painful diabetic neuropathy using distinct classes of drugs, with an emphasis on avoiding opioid use, have been issued. Although our understanding of the complexities of diabetic neuropathy has substantially evolved over the past decade, the distinct mechanisms underlying neuropathy in type 1 and type 2 diabetes remains unknown. Future discoveries on disease pathogenesis will be crucial to successfully address all aspects of diabetic neuropathy, from prevention to treatment.

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Fig. 1: Patterns of nerve injury in diabetic neuropathy.
Fig. 2: The peripheral nervous system and alterations in diabetic neuropathy.
Fig. 3: Diabetic neuropathy pathogenesis.
Fig. 4: Central and peripheral mechanisms contributing to neuropathic pain in diabetic neuropathy.
Fig. 5: NCS and biopsy study in diabetic neuropathy.
Fig. 6: Treatment of painful diabetic neuropathy.

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Acknowledgements

E.L.F. acknowledges support from the NIH (R24DK082841 and R01D107956) and the NovoNordisk Foundation (NNF14OC0011633). B.C.C. acknowledges support from the NIH (K23NS079417 and R01DK115687) and a VA Clinical Science Research and Development (CSRD) Merit (CX001504). R.P.B. acknowledges support from the NIH (R01D107956). D.W.Z. acknowledges support from the Canadian Institutes of Health Research (RN192747-298730) and Diabetes Canada (RN271389-OG-3-15-5025-DZ). D.E.W. acknowledges support from the NIH (R01NS0433314-14). D.L.B. acknowledges support from the NovoNordisk Foundation (NNF14OC0011633) and the Wellcome Trust (102645/Z/13/Z, 202747/Z/16/Z) and is a member of the DOLORisk Consortium funded by the European Commission Horizon 2020 (ID633491). J.W.R. acknowledges support from the NIH (R01DK107007), the US Department of Veterans Affairs (101RX001030), the Diabetes Action Research and Education Foundation and the Baltimore Geriatric Research Education and Clinical Center (GRECC). The authors thank S. Sakowski Jacoby for manuscript preparation and editorial assistance.

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Authors and Affiliations

  1. Department of Neurology, University of Michigan, Ann Arbor, MI, USA

    Eva L. Feldman & Brian C. Callaghan

  2. Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND), University of Michigan, Ann Arbor, MI, USA

    Rodica Pop-Busui

  3. Division of Neurology, Department of Medicine and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada

    Douglas W. Zochodne

  4. Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA

    Douglas E. Wright

  5. Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK

    David L. Bennett

  6. Division of Neurology, Department of Medicine, University of Toronto and University Health Network, Toronto, Ontario, Canada

    Vera Bril

  7. Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

    Vera Bril

  8. Department of Neurology, University of Maryland and VA Maryland Health Care System, Baltimore, MD, USA

    James W. Russell

  9. M. V. Hospital for Diabetes, Royapuram, Chennai, India

    Vijay Viswanathan

Authors
  1. Eva L. Feldman
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  2. Brian C. Callaghan
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  3. Rodica Pop-Busui
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  4. Douglas W. Zochodne
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  7. Vera Bril
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  8. James W. Russell
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  9. Vijay Viswanathan
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Contributions

Introduction (E.L.F.); Epidemiology (B.C.C. and E.L.F.); Diagnosis, screening and prevention (B.C.C. and V.B.); Mechanisms/pathophysiology of diabetic neuropathy (D.W.Z., D.E.W. and E.L.F.); Mechanisms/pathophysiology of pain (D.L.B.); Management (R.P.-B., J.W.R. and E.L.F.); Quality of life (V.V.); Outlook (E.L.F.); Overview of the Primer (E.L.F.).

Corresponding author

Correspondence to Eva L. Feldman.

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Competing interests

B.C.C. consults for a Patient-Centered Outcomes Research Institute (PCORI) grant, the Immune Tolerance Network and DynaMed and performs medical legal consultations. D.L.B. has undertaken consultancy work on behalf of Oxford Innovation for Abide, Biogen, GSK, Lilly, Mitsubishi Tanabe, Mundipharma, Teva and Theranexus. All other authors declare no competing interests.

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Feldman, E.L., Callaghan, B.C., Pop-Busui, R. et al. Diabetic neuropathy. Nat Rev Dis Primers 5, 41 (2019). https://doi.org/10.1038/s41572-019-0092-1

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