Diabetic neuropathy: a comprehensive review of prevalence, screening and diagnostic approaches, clinical symptoms, complications and evidence-based management strategies
DOI:
https://doi.org/10.18203/2320-6012.ijrms20260655Keywords:
Diabetic neuropathy, Type 1 diabetes, Diagnostic approachAbstract
Diabetic neuropathy (DN) is a frequent and significant complication of diabetes that has a major impact on patients' quality of life and contributes to higher rates of illness and mortality. DN impacts approximately 50% of people who have diabetes. It is characterized by distal symmetric polyneuropathy, leading to sensory loss, pain, and challenges with movement. This condition often results in diabetic foot ulcers and the amputation of lower limbs. The onset of diabetic neuropathy is influenced by multiple factors, such as elevated blood sugar levels, dyslipidemia, oxidative stress, mitochondrial issues, and inflammation, all of which can damage peripheral nerves. Despite extensive research, no effective treatments that modify the disease have been identified, and existing methods primarily focus on symptom management. This review explores the complex mechanisms of diabetic neuropathy and highlights recent advancements in its diagnosis and treatment. Recent diagnostic techniques, such as corneal confocal microscopy and biomarker-based tests, have improved the early detection of conditions and the provision of prompt treatment. Modifications in lifestyle and methods that include various healthcare professionals can enhance patient outcomes. Despite significant progress, further research is necessary to develop treatments that can effectively halt or reverse the progression of the disease, which would improve the quality of life for individuals with DN. This review offers a complete summary of the current knowledge and future trends in diabetic nephropathy research and management.
Metrics
References
World Health Organization. Global report on diabetes. Geneva: WHO. 2016. Available at: https://www.who.int/publications/i/item/9789241565257. Accessed on 15 November 2025.
International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Brussels: IDF. 2019. Available at: https://diabetesatlas.org. Accessed on 15 November 2025.
Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28(4):956-62. DOI: https://doi.org/10.2337/diacare.28.4.956
Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521-34.
Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285-93. DOI: https://doi.org/10.2337/dc10-1303
Hansen C, Määttä L, Andersen S, Charles M. The epidemiology of diabetic neuropathy. Adv Pathophysiol Clin Manage. 2023;5:36. DOI: https://doi.org/10.1007/978-3-031-15613-7_2
Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus--present and future perspectives. Nat Rev Endocrinol. 2011;8(4):228-36. DOI: https://doi.org/10.1038/nrendo.2011.183
Shiferaw WS, Akalu, TY, Work Y, Aynalem YA. Prevalence of diabetic peripheral neuropathy in Africa: a systematic review and meta-analysis. BMC Endocr Disord. 2020;20:49. DOI: https://doi.org/10.1186/s12902-020-0534-5
Iqbal Z, Azmi S, Yadav R, Ferdousi M, Kumar M, Cuthbertson DJ, et al. Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy. Clin Ther. 2018;40(6):828-49. DOI: https://doi.org/10.1016/j.clinthera.2018.04.001
Bradley D, Hsueh W. Type 2 Diabetes in the Elderly: Challenges in a Unique Patient Population. J Geriatr Med Gerontol. 2016;2(2):14. DOI: https://doi.org/10.23937/2469-5858/1510014
Reed J, Bain S, Kanamarlapudi V. A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives. Diabetes Metab Syndr Obes. 2021;14:3567-602. DOI: https://doi.org/10.2147/DMSO.S319895
Hicks C, Selvin E. Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes. Curr Diab Rep. 2019;19(10):86.
Alleman C, Westerhout K, Hensen M, Chambers C, Stoker M, Long S, et al. Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature. Diabetes Res Clin Pract. 2015;109(2):215-25. DOI: https://doi.org/10.1016/j.diabres.2015.04.031
Ristikj-Stomnaroska D, Risteska-Nejashmikj V, Papazova M. Role of Inflammation in the Pathogenesis of Diabetic Peripheral Neuropathy. Open Access Maced J Med Sci. 2019;7(14):2267-70. DOI: https://doi.org/10.3889/oamjms.2019.646
American Diabetes Association. Standards of Medical Care in Diabetes-2020 Abridged for Primary Care Providers. Clin Diabetes. 2020;38(1):10-38. DOI: https://doi.org/10.2337/cd20-as01
Boulton A. Diabetic neuropathy and foot complications. Handb Clin Neurol. 2014;126:97-107. DOI: https://doi.org/10.1016/B978-0-444-53480-4.00008-4
Magliano D, Boyko E; IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS. 10th edition. Brussels: International Diabetes Federation. 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK581934/. Accessed on 15 November 2025.
Roglic G. WHO Global report on diabetes: A summary. Int J Noncommunicable Dis. 2016;1(1):3-8. DOI: https://doi.org/10.4103/2468-8827.184853
Nkonge K, Nkonge D, Nkonge T. Screening for diabetic peripheral neuropathy in resource-limited settings. Diabetol Metab Syndr. 2023;15(1):55. DOI: https://doi.org/10.1186/s13098-023-01032-x
Ardeleanu V, Toma A, Pafili K, Papanas N, Motofei I, Diaconu CC, et al. Current Pharmacological Treatment of Painful Diabetic Neuropathy: A Narrative Review. Medicina (Kaunas). 2020;56(1):25. DOI: https://doi.org/10.3390/medicina56010025
Dubský M, Sojáková D, Fejfarová V, Jude EB. Diabetic Peripheral Neuropathy: New Diagnostics and Treatment Perspectives. Drugs Aging. 2026;43(1):29-48. DOI: https://doi.org/10.1007/s40266-025-01267-5
Jia Z, Wang T, Wang H. Significance of quantitative sensory testing in the diagnosis of diabetic peripheral neuropathy. J Clin Neurophysiol. 2014;31(5):437-40. DOI: https://doi.org/10.1097/WNP.0000000000000086
Samolis A, Troupis T, Politis C, Pantazis N, Triantafyllou G, Tsakotos G, et al. Intraepidermal Nerve Fiber Density as an Indicator of Neuropathy Predisposition: A Systematic Review with Meta-Analysis. Diagnostics (Basel). 2025;15(11):1311. DOI: https://doi.org/10.3390/diagnostics15111311
Gad H, Petropoulos IN, Khan A, Ponirakis G, MacDonald R, Alam U, et al. Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta-analysis. J Diabetes Investig. 2022;13(1):134-47. DOI: https://doi.org/10.1111/jdi.13643
Fujita Y, Murakami T, Nakamura A. Recent Advances in Biomarkers and Regenerative Medicine for Diabetic Neuropathy. Int J Mol Sci. 2021;22(5):2301. DOI: https://doi.org/10.3390/ijms22052301
Ziegler D, Papanas N, Vinik AI, Shaw JE. Epidemiology of polyneuropathy in diabetes and prediabetes. Handbook Clin Neurol. 2014;126:3-22. DOI: https://doi.org/10.1016/B978-0-444-53480-4.00001-1
Feldman E, Callaghan B, Pop-Busui R, Zochodne D, Wright D, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):41. DOI: https://doi.org/10.1038/s41572-019-0092-1
Amelia R, Wahyuni A, Yunanda Y, Fujiati I, Harahap J, Wijaya H, et al. Early Detection of Diabetic Peripheral Neuropathy in Diabetic Patients: A Cross-Sectional Study. Curr Diabetes Rev. 2024;21(2):e280324228439. DOI: https://doi.org/10.2174/0115733998297210240325062747
Hicks C, Selvin E. Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes. Curr Diab Rep. 2019;19(10):86. DOI: https://doi.org/10.1007/s11892-019-1212-8
Tannus L, Cobas R. Autonomic neuropathy in diabetes. Arch Endocrinol Metab. 2025;70:e250406. DOI: https://doi.org/10.20945/2359-4292-2025-0406
Afridi Z, Rauf S, Ashraf S, Haque M. Transformative Advances in Continuous Glucose Monitoring and the Impact of FDA Over-the-Counter Approval on Diabetes Care. Health Sci Rep. 2025;8(4):e70747. DOI: https://doi.org/10.1002/hsr2.70747
Strand N, Anderson M, Attanti S, Gill B, Wie C, Dawodu A, et al. Diabetic Neuropathy: Pathophysiology Review. Curr Pain Headache Rep. 2024;28(6):481-7. DOI: https://doi.org/10.1007/s11916-024-01243-5
Lim J, Ng N, Thomas C. Prevention and treatment of diabetic foot ulcers. J R Soc Med. 2017;110(3):104-9. DOI: https://doi.org/10.1177/0141076816688346
Sanjeeviraj S, Subburaj A, Aluri S, Thakku Sekar B, Jalan M, Joseph A. A Cohort Study on the Outcome of Diabetic Foot Ulcers. Cureus. 2023;15(10):e48030. DOI: https://doi.org/10.7759/cureus.48030
Wu S, Driver V, Wrobel J, Armstrong D. Foot ulcers in the diabetic patient, prevention and treatment. Vasc Health Risk Manag. 2007;3(1):65-76.
M Murphy-Lavoie HM, Ramsey A, Nguyen M, Vadakekut ES. Diabetic Foot Infections. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2025.
Aditya C, Bukke S, Anitha K, Meeraraje P, Goruntla N, Yadesa T, et al. A comprehensive review on diabetic foot ulcer addressing vascular insufficiency, impaired immune response, and delayed wound healing mechanisms. Front Pharmacol. 2025;16:1622055. DOI: https://doi.org/10.3389/fphar.2025.1622055
Jeffcoate W, Boyko E, Game F, Cowled P, Senneville E, Fitridge R. Causes, prevention, and management of diabetes-related foot ulcers. Lancet Diabetes Endocrinol. 2024;12(7):472-82. DOI: https://doi.org/10.1016/S2213-8587(24)00110-4
Sugimoto K, Yasujima M, Yagihashi S. Role of advanced glycation end products in diabetic neuropathy. Curr Pharm Des. 2008;14(10):953-61. DOI: https://doi.org/10.2174/138161208784139774
Sher E, Džidić-Krivić A, Karahmet A, Beća-Zećo M, Farhat EK, Softić A, et al. Novel therapeutical approaches based on neurobiological and genetic strategies for diabetic polyneuropathy - A review. Diabetes Metab Syndr. 2023;17(11):102901. DOI: https://doi.org/10.1016/j.dsx.2023.102901
Smith S, Normahani P, Lane T, Hohenschurz-Schmidt D, Oliver N, Davies A. Prevention and Management Strategies for Diabetic Neuropathy. Life (Basel). 2022;12(8):1185. DOI: https://doi.org/10.3390/life12081185
Yang Y, Zhao B, Wang Y, Lan H, Liu X, Hu Y, et al. Diabetic neuropathy: cutting-edge research and future directions. Signal Transduction and Targeted Therapy. 2025;10(1):132. DOI: https://doi.org/10.1038/s41392-025-02175-1
Callaghan B, Cheng H, Stables C, Smith A, Feldman E. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521-34. DOI: https://doi.org/10.1016/S1474-4422(12)70065-0
Blaibel D, Fernandez C, Pappachan J. Non-pharmacological interventions for diabetic peripheral neuropathy: Are we winning the battle? World J Diabetes. 2024;15(4):579-85. DOI: https://doi.org/10.4239/wjd.v15.i4.579
Elafros M, Callaghan B. Diabetic Neuropathies. Continuum (Minneap Minn). 2023;29(5):1401-17. DOI: https://doi.org/10.1212/CON.0000000000001291
Bönhof G, Herder C, Ziegler D. Diagnostic Tools, Biomarkers, and Treatments in Diabetic polyneuropathy and Cardiovascular Autonomic Neuropathy. Curr Diabetes Rev. 2022;18(5):e120421192781. DOI: https://doi.org/10.2174/1573399817666210412123740
Gabbay K. Aldose reductase inhibition in the treatment of diabetic neuropathy: where are we in 2004? Curr Diab Rep. 2004;4(6):405-8. DOI: https://doi.org/10.1007/s11892-004-0047-z
Ola M, Nawaz M, Khan H, Alhomida A. Neurodegeneration and neuroprotection in diabetic retinopathy. Int J Mol Sci. 2013;14(2):2559-72. DOI: https://doi.org/10.3390/ijms14022559
de Figueiredo C, Dos Reis L. Stem Cell Therapies for the Treatment of Diabetic Neuropathies: Future Perspectives. Curr Diabetes Rev. 2021;17(1):2-10. DOI: https://doi.org/10.2174/1573399816666200417121915
Yagihashi S, Yamagishi S, Wada R. Pathology and pathogenetic mechanisms of diabetic neuropathy: correlation with clinical signs and symptoms. Diabetes Res Clin Pract. 2007;77:S184-9. DOI: https://doi.org/10.1016/j.diabres.2007.01.054
Barsotti E, Goodman B, Samuelson R, Carvour M. A Scoping Review of Wearable Technologies for Use in Individuals With Intellectual Disabilities and Diabetic Peripheral Neuropathy. J Diabetes Sci Technol. 2025;19(4):1082-96. DOI: https://doi.org/10.1177/19322968241231279