Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy
Abstract
Diabetic sensorimotor peripheral neuropathy (DSPN) is a serious complication of diabetes mellitus and is associated with increased mortality, lower-limb amputations and distressing painful neuropathic symptoms (painful DSPN). Our understanding of the pathophysiology of the disease has largely been derived from animal models, which have identified key potential mechanisms. However, effective therapies in preclinical models have not translated into clinical trials and we have no universally accepted disease-modifying treatments. Moreover, the condition is generally diagnosed late when irreversible nerve damage has already taken place. Innovative point-of-care devices have great potential to enable the early diagnosis of DSPN when the condition might be more amenable to treatment. The management of painful DSPN remains less than optimal; however, studies suggest that a mechanism-based approach might offer an enhanced benefit in certain pain phenotypes. The management of patients with DSPN involves the control of individualized cardiometabolic targets, a multidisciplinary approach aimed at the prevention and management of foot complications, and the timely diagnosis and management of neuropathic pain. Here, we discuss the latest advances in the mechanisms of DSPN and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Diabetic neuropathy might only be diagnosed after patients experience substantial nerve impairment.
“For instance, diabetic retinopathy can go undetected until it has caused irreversible vision damage (6), and diabetic neuropathy might only be diagnosed after patients experience substantial nerve impairment (7).”
From Generative artificial intelligence in predictive analysis of diabetes and its complications: a narrative review (2025) · cites this paper as [7]
Cites
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769 · see citing works
Glucose control and vascular complications in veterans with type 2 diabetes
Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P. D., Zieve, F. J., Marks, J., Davis, S. N., Hayward, R., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808431 · Cited by 4,762 · see citing works
Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis
Finnerup, N. B., Attal, N., Haroutounian, S., McNicol, E., Baron, R., Dworkin, R. H., Gilron, I., Haanpää, M., Hansson, P., Jensen, T. S., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70251-0 · Cited by 3,980 · see citing works
Central sensitization: a generator of pain hypersensitivity by central neural plasticity
Latremoliere, A., & Woolf, C. J. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2009.06.012 · Cited by 3,913 · see citing works
Effect of a multifactorial intervention on mortality in type 2 diabetes
Gæde, P., Lund-Andersen, H., Parving, H.-H., & Pedersen, O. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706245 · Cited by 3,489 · see citing works
Tesfaye, S., Boulton, A. J. M., Dyck, P. J., Freeman, R., Horowitz, M., Kempler, P., Lauria, G., Malik, R. A., Spallone, V., Vinik, A., et al. (2010) · Diabetes Care · doi:10.2337/dc10-1303 · Cited by 2,690 · see citing works
Self-citationFreynhagen, R., Baron, R., Gockel, U., & Tölle, T. R. (2006) · Current Medical Research and Opinion · doi:10.1185/030079906x132488 · Cited by 2,280 · see citing works
Sex differences in pain: a brief review of clinical and experimental findings
Bartley, E. J., & Fillingim, R. B. (2013) · British Journal of Anaesthesia · doi:10.1093/bja/aet127 · Cited by 2,168 · see citing works
Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths
Bohnert, A. S. B. (2011) · JAMA · doi:10.1001/jama.2011.370 · Cited by 1,509 · see citing works
Dyck, P. J., Kratz, K. M., Karnes, J. L., Litchy, W. J., Klein, R., Pach, J. M., Wilson, D. M., O'Brien, P. C., & Melton, L. J. (1993) · Neurology · doi:10.1212/wnl.43.4.817 · Cited by 1,482 · see citing works
(2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00291-0 · Cited by 1,029 · see citing works
New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain
Feldman, E. L., Nave, K.-A., Jensen, T. S., & Bennett, D. L. H. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.005 · Cited by 915 · see citing works
Abbott, C. A., Malik, R. A., van Ross, E. R. E., Kulkarni, J., & Boulton, A. J. M. (2011) · Diabetes Care · doi:10.2337/dc11-1108 · Cited by 868 · see citing works
Tesfaye, S., Stevens, L. K., Stephenson, J. M., Fuller, J. H., Plater, M., Ionescu-Tirgoviste, C., Nuber, A., Pozza, G., & Ward, J. D. (1996) · Diabetologia · doi:10.1007/s001250050586 · Cited by 695 · see citing works
Self-citationAustin, P. J., & Moalem-Taylor, G. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.08.013 · Cited by 607 · see citing works
Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia
Lunn, M. P., Hughes, R. A., & Wiffen, P. J. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007115.pub3 · Cited by 565 · see citing works
Tesfaye, S., Vileikyte, L., Rayman, G., Sindrup, S. H., Perkins, B. A., Baconja, M., Vinik, A. I., Boulton, A. J. M., & Neuropathy, O. B. O. T. T. E. P. O. D. (2011) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1225 · Cited by 410 · see citing works
Self-citationKluding, P. M., Pasnoor, M., Singh, R., Jernigan, S., Farmer, K., Rucker, J., Sharma, N. K., & Wright, D. E. (2012) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2012.05.007 · Cited by 370 · see citing works
Tesfaye, S., Wilhelm, S., Lledo, A., Schacht, A., Tölle, T., Bouhassira, D., Cruccu, G., Skljarevski, V., & Freynhagen, R. (2013) · Pain · doi:10.1016/j.pain.2013.05.043 · Cited by 311 · see citing works
Self-citationJaiswal, M., Divers, J., Dabelea, D., Isom, S., Bell, R. A., Martin, C. L., Pettitt, D. J., Saydah, S., Pihoker, C., Standiford, D. A., et al. (2017) · Diabetes Care · doi:10.2337/dc17-0179 · Cited by 303 · see citing works
Dyslipidemia-Induced Neuropathy in Mice
Vincent, A. M., Hayes, J. M., McLean, L. L., Vivekanandan-Giri, A., Pennathur, S., & Feldman, E. L. (2009) · Diabetes · doi:10.2337/db09-0047 · Cited by 264 · see citing works
Andersen, S. T., Witte, D. R., Dalsgaard, E.-M., Andersen, H., Nawroth, P., Fleming, T., Jensen, T. M., Finnerup, N. B., Jensen, T. S., Lauritzen, T., et al. (2018) · Diabetes Care · doi:10.2337/dc17-2062 · Cited by 248 · see citing works
Mielke, M. M., Frank, R. D., Dage, J. L., Jeromin, A., Ashton, N. J., Blennow, K., Karikari, T. K., Vanmechelen, E., Zetterberg, H., Algeciras-Schimnich, A., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.2293 · Cited by 244 · see citing works
Braffett, B. H., Gubitosi-Klug, R. A., Albers, J. W., Feldman, E. L., Martin, C. L., White, N. H., Orchard, T. J., Lopes-Virella, M., Lachin, J. M., Pop-Busui, R., et al. (2020) · Diabetes · doi:10.2337/db19-1046 · Cited by 221 · see citing works
Pop-Busui, R., Lu, J., Brooks, M. M., Albert, S., Althouse, A. D., Escobedo, J., Green, J., Palumbo, P., Perkins, B. A., Whitehouse, F., et al. (2013) · Diabetes Care · doi:10.2337/dc13-0012 · Cited by 167 · see citing works
Nonnarcotic Methods of Pain Management
Finnerup, N. B. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1807061 · Cited by 153 · see citing works
Gylfadottir, S. S., Christensen, D. H., Nicolaisen, S. K., Andersen, H., Callaghan, B. C., Itani, M., Khan, K. S., Kristensen, A. G., Nielsen, J. S., Sindrup, S. H., et al. (2020) · Pain · doi:10.1097/j.pain.0000000000001744 · Cited by 151 · see citing works
Bouhassira, D., Wilhelm, S., Schacht, A., Perrot, S., Kosek, E., Cruccu, G., Freynhagen, R., Tesfaye, S., Lledó, A., Choy, E., et al. (2014) · Pain · doi:10.1016/j.pain.2014.08.020 · Cited by 132 · see citing works
Self-citationTreating pain in diabetic neuropathy: current and developmental drugs
Alam, U., Sloan, G., & Tesfaye, S. (2020) · Drugs · doi:10.1007/s40265-020-01259-2 · Cited by 104 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects
Ru, Q., Li, Y., Chen, L., Wu, Y., Min, J., & Wang, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01969-z · Cited by 724 · see citing works
Yang, Q., Bee, Y. M., Lim, C. C., Sabanayagam, C., Yim-Lui Cheung, C., Wong, T. Y., Ting, D. S. W., Lim, L.-L., Li, H., He, M., et al. (2025) · eClinicalMedicine · doi:10.1016/j.eclinm.2025.103089 · Cited by 38 · see citing works
Chronic liver diseases and erectile dysfunction
Zang, G., Sun, X., Sun, Y., Zhao, Y., Dong, Y., Pang, K., Cheng, P., Wang, M., & Zheng, Y. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2022.1092353 · Cited by 21 · see citing works
Osonuga, A., Olawade, D. B., Gore, M., Rotifa, O. B., Egbon, E., Chinwah, V., & Boussios, S. (2025) · Annals of Translational Medicine · doi:10.21037/atm-25-62 · Cited by 4 · see citing works
- Authors
- Sloan, G., Selvarajah, D., & Tesfaye, S.
- Affiliations
- Royal Hallamshire Hospital (GB)
- Corresponding author
- Tesfaye, Solomon
- Venue
- Nature Reviews Endocrinology
- Published
- 2021-05-28
- Volume
- 17
- Issue
- 7
- Pages
- 400-420
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W3165754381
- Cited by
- 534
- References
- 30
- Citations by year
- 2026: 105 · 2025: 123 · 2024: 130 · 2023: 95 · 2022: 70 · 2021: 11
- FWCI
- 10.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- diabetic neuropathic pain, pathophysiology, neuropathic pain mechanisms, early diagnosis, point-of-care testing, disease-modifying therapy, foot complications, multidisciplinary management, animal models
- MeSH terms
- Amputation, Surgical, Animals, Diabetic Neuropathies, Humans, Neuralgia, Neuromuscular Diseases, Peripheral Nervous System Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
