EARLY PREDICTORS AND PREVENTION STRATEGIES FOR DIABETIC NEUROPATHY, A NARRATIVE REVIEW
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.5949Keywords:
Diabetic Neuropathy, Early Predictors, Prevention, Screening, Small‑Fiber NeuropathyAbstract
Diabetic neuropathy (DN), encompassing distal symmetric polyneuropathy, small‑fiber and autonomic neuropathies, is highly prevalent across the spectrum of dysglycemia and causes neuropathic pain, sensory loss, autonomic dysfunction, foot ulceration, and increased morbidity and mortality. Early detection of subclinical nerve injury and identification of modifiable risk factors permit timely prevention and may reduce long‑term complications. The aim of this study is to synthesize evidence from recent studies on early clinical, metabolic, and paraclinical predictors of diabetic neuropathy and to summarize practical, implementable prevention and screening strategies. The study was conducted as a structured narrative review modeled after the framework of an original research article. The analysis was based on a review of the literature indexed in PubMed concerning early predictors, paraclinical markers, point‑of‑care diagnostics for subclinical neuropathy, primary prevention and multifactorial risk‑reduction strategies recommended in the literature. Small‑fiber autonomic dysfunction, which frequently precede clinically overt large‑fiber loss, is detectable by corneal confocal microscopy, intraepidermal nerve‑fiber density, quantitative sensory testing, and autonomic measures (HRV, cardiovascular autonomic reflex tests), as well as validated devices, enabling earlier risk stratification. Prevention strategies supported or recommended across sources include early risk stratification with combined small‑ and large‑fiber testing, intensive glycemic control,structured lifestyle interventions and comprehensive cardiometabolic management. Multifactorial programs and targeted early interventions are promising but require sensitive endpoints and longer follow‑up to confirm impact on hard outcomes. Prevention of diabetic neuropathy relies on early recognition of clinical and subclinical predictors, incorporation of sensitive screening tools and prompt multifactorial risk modification. Implementation of combined screening and structured education models may improve early detection and reduce downstream morbidity, but prospective trials using sensitive diagnostic endpoints are needed to demonstrate disease modification.
References
Selvarajah, D., Kar, D., Khunti, K., Davies, M., Scott, A., Walker, J., & Tesfaye, S. (2019). Diabetic peripheral neuropathy: Advances in diagnosis and strategies for screening and early intervention [Accepted manuscript]. White Rose Research Online. https://eprints.whiterose.ac.uk/id/eprint/152925/
Dillon, B. R., Ang, L., & Pop‑Busui, R. (2024). Spectrum of diabetic neuropathy: New insights in diagnosis and treatment. Annual Review of Medicine, 75, 293–306. https://doi.org/10.1146/annurev-med-043021-033114
Selvarajah, D., Cash, T., Davies, J., Price, P., Alam, U., Maddison, P., et al. (2015). SUDOSCAN: A simple, rapid, and objective method with potential for screening for diabetic peripheral neuropathy. PLOS ONE, 10(10), e0138224. https://doi.org/10.1371/journal.pone.0138224
Diabetes Control and Complications Trial Research Group. (1993). The effect of intensive treatment of diabetes on the development and progression of long‑term complications in insulin‑dependent diabetes mellitus. New England Journal of Medicine, 329(14), 977–986. https://doi.org/10.1056/NEJM199309303291401
Pritchard, N., Edwards, K., Russell, A., Perkins, B. A., Malik, R. A., & Efron, N. (2015). Corneal confocal microscopy predicts 4‑year incident peripheral neuropathy in type 1 diabetes. Diabetes Care, 38(3), 671–675. https://doi.org/10.2337/dc14-1640
Lee, J. A., Halpern, E. M., Lovblom, L. E., Yeung, E., Bril, V., & Perkins, B. A. (2014). Reliability and validity of a point‑of‑care sural nerve conduction device for identification of diabetic neuropathy. PLOS ONE, 9(4), e86515. https://doi.org/10.1371/journal.pone.0086515
Callaghan, B. C., Xia, R., Banerjee, M., et al. (2016). Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status. Diabetes Care, 39(5), 801–808. https://doi.org/10.2337/dc15-2223
Pop‑Busui, R., Boulton, A. J. M., Feldman, E. L., Bril, V., Freeman, R., Malik, R. A., et al. (2017). Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care, 40(1), 136–154. https://doi.org/10.2337/dc16-2042
Wiggin, T. D., Sullivan, K. A., Pop‑Busui, R., Amato, A., Sima, A. A., & Feldman, E. L. (2009). Elevated triglycerides correlate with progression of diabetic neuropathy. Diabetes, 58(6), 1634–1640. https://doi.org/10.2337/db08-1446
Vinik, A. I., Megerian, J. T., & Gozani, S. (2006). Diabetic nerve conduction abnormalities in the primary care setting. Diabetes Technology & Therapeutics, 8(6), 654–662. https://doi.org/10.1089/dia.2006.8.654
Binns‑Hall, O., Selvarajah, D., Sanger, D., Walker, J., Scott, A., & Tesfaye, S. (2018). One‑stop microvascular screening service: An effective model for the early detection of diabetic peripheral neuropathy and the high‑risk foot. Diabetic Medicine, 35(7), 887–894. https://doi.org/10.1111/dme.13646
Vincent, A. M., Callaghan, B. C., Smith, A. L., & Feldman, E. L. (2011). Diabetic neuropathy: Cellular mechanisms as therapeutic targets. Nature Reviews Neurology, 7(10), 573–583. https://doi.org/10.1038/nrneurol.2011.135
Pop‑Busui, R., Ang, L., Holmes, C., et al. (2016). Inflammation as a therapeutic target for diabetic neuropathies. Current Diabetes Reports, 16(6), 29. https://doi.org/10.1007/s11892-016-0756-0
Gaede, P., Vedel, P., Larsen, N., Jensen, G. V. H., Parving, H. H., & Pedersen, O. (2003). Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes (Steno‑2). New England Journal of Medicine, 348(5), 383–393. https://doi.org/10.1056/NEJMoa021778
Ismail‑Beigi, F., Craven, T., Banerji, M. A., et al.; ACCORD Trial Group. (2010). Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomized trial. The Lancet, 376(9739), 419–430. https://doi.org/10.1016/S0140-6736(10)60576-4
Singleton, J. R., Marcus, R. L., Lessard, M. K., Jackson, J. E., & Smith, A. G. (2015). Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients. Annals of Neurology, 77(1), 146–153. https://doi.org/10.1002/ana.24399
Horton, E. S., Chen, H., Nathan, D. M., et al. (2017). Effects of a long‑term lifestyle modification programme on peripheral neuropathy in overweight or obese adults with type 2 diabetes: The Look AHEAD study. Diabetologia, 60(5), 980–988. https://doi.org/10.1007/s00125-017-4216-6
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Anna Justkowska-Gebauer, Wojciech Krzysztof Cyran, Tatsiana Matsiusheuskaya, Weronika Cionżyńska, Krzysztof Machnik, Bartosz Gaweł, Beata Tekieli, Maksymilian Olesiński, Ewelina Chudyba, Michał Gebauer
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
