Diabetic neuropathy: A position statement by the American Diabetes Association
Open accessAbstract
Diabetic neuropathies are the most prevalent chronic complications of diabetes. This heterogeneous group of conditions affects different parts of the nervous system and presents with diverse clinical manifestations. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons: 1. Diabetic neuropathy is a diagnosis of exclusion. Nondiabetic neuropathies may be present in patients with diabetes and may be treatable by specific measures. 2. A number of treatment options exist for symptomatic diabetic neuropathy. 3. Up to 50% of diabetic peripheral neuropathies may be asymptomatic. If not recognized and if preventive foot care is not implemented, patients are at risk for injuries to their insensate feet. 4. Recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life. Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DSPN) and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy (CAN), are by far the most studied (1–4). There are several atypical forms of diabetic neuropathy as well (1–4). Patients with prediabetes may also develop neuropathies that are similar to diabetic neuropathies (5–10). Table 1 provides a comprehensive classification scheme for the diabetic neuropathies. View this table: Table 1 Classification for diabetic neuropathies Due to a lack of treatments that target the underlying nerve damage, prevention is the key component of diabetes care. Screening for symptoms and signs of diabetic neuropathy is also critical in clinical practice, as it may detect the earliest stages of neuropathy, enabling early intervention. Although screening for rarer atypical forms of diabetic neuropathy may be warranted, DSPN and autonomic neuropathy are the most common forms encountered in practice. The strongest available evidence regarding treatment pertains to these forms. This Position Statement is based on several recent technical reviews, to which the reader is referred for detailed discussion …
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Even in modern cohorts, glucose control is the strongest risk factor for DPN in T1D.
“and glucose control remains the strongest risk factor for DPN in T1D even in contemporary cohorts.417,542–544,547”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [543]
The Prevention > Glucose Control section reports that enhanced glucose control dramatically reduces distal symmetric polyneuropathy incidence in type 1 diabetes. The DSPN section also lists glycemia among associated factors. Neither passage ranks glucose control as the strongest risk factor or establishes that ranking in contemporary cohorts. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCardiovascular autonomic reflex tests (CARTs) involve several burdensome physiological maneuvers and have limited feasibility in clinical settings.
“CARTs involve several burdensome physiological maneuvers, including heart rate responses to deep breathing, the Valsalva maneuver, and changes in blood pressure in response to postural change [12].”
From Cardiovascular autonomic neuropathy defined by indices of heart rate variability is associated with cardiovascular disease: a longitudinal cohort study of participants with type 1 diabetes (2025) · cites this paper as [12]
The ‘Neuropathy End Points for Research and Clinical Trials’ section lists deep breathing, Valsalva, and standing as cardiovascular autonomic reflex-test maneuvers; the CAN section also describes assessing blood-pressure changes on standing. But the paper calls the reflex tests and maneuvers simple and describes related testing as feasible in the office. It does not support characterizing the maneuvers as burdensome or the tests as having limited clinical feasibility. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCKD and diabetic neuropathy have been widely studied, but the focus has been primarily on cardiac autonomic neuropathies, with few studies evaluating CKD and peripheral neuropathy.
“CKD and diabetic neuropathy have been widely studied, but the focus has been primarily on cardiac autonomic neuropathies, with few studies evaluating CKD and peripheral neuropathy.26–29”
From Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease (2020) · cites this paper as [27]
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What Do We Know and We Do Not Know About Cardiovascular Autonomic Neuropathy in Diabetes
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Self-citationPreventive Foot Care in People With Diabetes
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Self-citationDuloxetine for Patients with Diabetic Peripheral Neuropathic Pain: A 6-Month Open-Label Safety Study
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Self-citationAntidepressants in Neuropathic Pain
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Whither pathogenetic treatments for diabetic polyneuropathy?
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Self-citationEffect of Intensive Glycemic Therapy on Erectile Function in Men With Type 1 Diabetes
Wessells, H., Penson, D. F., Cleary, P. A., Rutledge, B. N., Lachin, J. M., McVary, K. T., Schade, D. S., & Sarma, A. V. (2011) · The Journal of Urology · doi:10.1016/j.juro.2010.12.098 · Cited by 91 · see citing works
Association of Subclinical Inflammation With Polyneuropathy in the Older Population
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Self-citationER Stress in Diabetic Peripheral Neuropathy: A New Therapeutic Target
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Self-citationEpidemiology and Natural History of Gastroparesis
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Association Between Cardiovascular Autonomic Neuropathy and Left Ventricular Dysfunction
Pop-Busui, R., Cleary, P. A., Braffett, B. H., Martin, C. L., Herman, W. H., Low, P. A., Lima, J. A. C., & Bluemke, D. A. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.10.028 · Cited by 88 · see citing works
Self-citationSmith, A. G., & Singleton, J. R. (2012) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/01.con.0000411568.34085.3e · Cited by 88 · see citing works
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Self-citationImmunotherapy for diabetic amyotrophy
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Clinical neuropathy scales in neuropathy associated with impaired glucose tolerance
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Body stature as a risk factor for diabetic sensory neuropathy
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Self-citationCombination pharmacotherapy for the treatment of neuropathic pain in adults
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Does Treatment With Duloxetine for Neuropathic Pain Impact Glycemic Control?
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Self-citation
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Feldman, E. L., Callaghan, B. C., Pop-Busui, R., Zochodne, D. W., Wright, D. E., Bennett, D. L., Bril, V., Russell, J. W., & Viswanathan, V. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0092-1 · Cited by 1,697 · see citing works
Self-citationNew Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain
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Self-citationDiabetes and hypertension: a position statement by the American Diabetes Association
de Boer, I. H., Bangalore, S., Benetos, A., Davis, A. M., Michos, E. D., Muntner, P., Rossing, P., Zoungas, S., & Bakris, G. (2017) · Diabetes Care · doi:10.2337/dci17-0026 · Cited by 714 · see citing works
Blonde, L., Umpierrez, G. E., Reddy, S. S., McGill, J. B., Berga, S. L., Bush, M., Chandrasekaran, S., DeFronzo, R. A., Einhorn, D., Galindo, R. J., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.08.002 · Cited by 507 · see citing works
Self-citationDiabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy
Iqbal, Z., Azmi, S., Yadav, R., Ferdousi, M., Kumar, M., Cuthbertson, D. J., Lim, J., Malik, R. A., & Alam, U. (2018) · Clinical Therapeutics · doi:10.1016/j.clinthera.2018.04.001 · Cited by 487 · see citing works
Self-citation11. Microvascular Complications and Foot Care: <i>Standards of Medical Care in Diabetes—2021</i>
American Diabetes Association (2021) · Diabetes Care · doi:10.2337/dc21-s011 · Cited by 395 · see citing works
Jaiswal, 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
Self-citationPetersen, E. A., Stauss, T. G., Scowcroft, J. A., Brooks, E. S., White, J. L., Sills, S. M., Amirdelfan, K., Guirguis, M. N., Xu, J., Yu, C., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.0538 · Cited by 277 · see citing works
Jensen, T. S., Karlsson, P., Gylfadottir, S. S., Andersen, S. T., Bennett, D. L., Tankisi, H., Finnerup, N. B., Terkelsen, A. J., Khan, K., Themistocleous, A. C., et al. (2021) · Brain · doi:10.1093/brain/awab079 · Cited by 265 · see citing works
Self-citationAndersen, 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
Self-citationBraffett, 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
Self-citation13. Children and Adolescents: <i>Standards of Medical Care in Diabetes—2021</i>
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12. Retinopathy, Neuropathy, and Foot Care: <i>Standards of Medical Care in Diabetes—2022</i>
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14. Children and Adolescents: Standards of Care in Diabetes—2025
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12. Retinopathy, Neuropathy, and Foot Care: <i>Standards of Care in Diabetes—2023</i>
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Gibbons, C. H., Giurini, J. M., Hilliard, M. E., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s012 · Cited by 169 · see citing works
12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Callaghan, B. C., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s012 · Cited by 176 · see citing works
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Cardiac Autonomic Neuropathy in Obesity, the Metabolic Syndrome and Prediabetes: A Narrative Review
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Treating 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
Andersen, S. T., Witte, D. R., Fleischer, J., Andersen, H., Lauritzen, T., Jørgensen, M. E., Jensen, T. S., Pop-Busui, R., & Charles, M. (2018) · Diabetes Care · doi:10.2337/dc18-1411 · Cited by 99 · see citing works
Self-citationJaiswal, M., Divers, J., Urbina, E. M., Dabelea, D., Bell, R. A., Pettitt, D. J., Imperatore, G., Pihoker, C., Dolan, L. M., Liese, A. D., et al. (2018) · Pediatric Diabetes · doi:10.1111/pedi.12633 · Cited by 90 · see citing works
Self-citationTruini, A., Spallone, V., Morganti, R., Tamburin, S., Zanette, G., Schenone, A., De Michelis, C., Tugnoli, V., Simioni, V., Manganelli, F., et al. (2018) · Pain · doi:10.1097/j.pain.0000000000001378 · Cited by 85 · see citing works
Tang, Y., Shah, H., Bueno Junior, C. R., Sun, X., Mitri, J., Sambataro, M., Sambado, L., Gerstein, H. C., Fonseca, V., Doria, A., et al. (2021) · Diabetes Care · doi:10.2337/dc20-1842 · Cited by 60 · see citing works
Self-citationJeyam, A., McGurnaghan, S. J., Blackbourn, L. A. K., McKnight, J. M., Green, F., Collier, A., McKeigue, P. M., & Colhoun, H. M. (2020) · Diabetes Care · doi:10.2337/dc19-1582 · Cited by 59 · see citing works
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Update on the Management of Diabetic Neuropathy
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Self-citationCardiovascular autonomic neuropathy: A silent killer with long reach
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“Yet, despite the proven prognostic value and current guideline recommendations for screening [11, 12].”
Self-citation
- Authors
- Pop-Busui, R., Boulton, A. J. M., Feldman, E. L., Bril, V., Freeman, R., Malik, R. A., Sosenko, J. M., & Ziegler, D.
- Affiliations
- Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
- Manchester Royal Infirmary (GB)
- University of Michigan (US)
- University of Toronto (CA)
- Harvard University (US)
- Cornell University (US)
- University of Miami (US)
- Deutsches Diabetes-Zentrum e.V. (DE)
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2016-12-10
- Volume
- 40
- Issue
- 1
- Pages
- 136-154
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC6977405
- OpenAlex
- W2561727131
- Cited by
- 2,602
- References
- 236
- Citations by year
- 2026: 312 · 2025: 340 · 2024: 316 · 2023: 318 · 2022: 333 · 2021: 320 · 2020: 271 · 2019: 181 · 2018: 153 · 2017: 53 · 2016: 2 · 2012: 1
- FWCI
- 15.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107956)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Keywords
- diabetic neuropathy, distal symmetric polyneuropathy, diabetic autonomic neuropathy, cardiac autonomic neuropathy, diabetic peripheral neuropathy, neuropathy screening, neuropathy prevention, foot care, prediabetes, neuropathy classification, neuropathy treatment
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