ABSTRACT

INTRODUCTION. Diabetic polyneuropathy is one of the most frequent and disabling complications of diabetes mellitus, exerting a profound impact on both life expectancy and quality of life. In the context of the rapidly increasing prevalence of diabetes worldwide and in Russia, the timely diagnosis and effective management of diabetic polyneuropathy have become an urgent clinical priority.

AIM. To consider summarizes current concepts of pathogenesis, classification, diagnostic algorithms, and therapeutic strategies for diabetic polyneuropathy, emphasizing an interdisciplinary perspective.

MAIN CONTENT OF THE REVIEW. Particular attention is given to the importance of early detection, which can be achieved through validated clinical scales such as the Neuropathy Symptom Score (NSS) and Total Symptom Score (TSS), as well as simple screening tools such as the Ipswich Touch Test. The integration of these instruments into routine practice contributes to the standardization of diagnostics and enables the objective assessment of symptom dynamics during treatment. The therapeutic section focuses on pathogenetically based approaches, with α-lipoic acid, B vitamins, and ipidacrine (Neiromidin®) playing a central role. Ipidacrine, in particular, has demonstrated efficacy in improving neuromuscular transmission, enhancing sensory function, and reducing pain severity, as supported by several clinical studies.

CONCLUSION. The implementation of algorithm-based diagnostic and therapeutic approaches, the early use of pathogenetically targeted agents, and the development of personalized management strategies open new prospects for reducing the risk of severe complications and improving the quality of life in patients with diabetic polyneuropathy.

KEYWORDS: diabetic neuropathies, ipidacrine, diagnostic and therapeutic algorithm

For citation: Rachin A.P., Rachin S.A., Sharov M.N., Parsamyan R.R., Karpov S.M. Diagnosis and Management of Diabetic Polyneuropathy: An Updated Algorithmic Approach. A Review. Comorbidity Neurology. 2025; 2 (3): 66-77. https://doi.org/10.62505/3034-185x-2025-2-3-66-77 (In Russ.)

*For correspondence: Andrei P. Rachin, Dr. Sci. (Med.), Professor, President of the National Association of Experts in Comorbid Neurology, Moscow, Russia, e-mail: 7851377@gmail.com

REFERENCES

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

2. Dedov I.I., Shestakova M.V., Mayorov A.Yu. et al. Standards of Specialized Diabetes Care. Diabetes mellitus. 2023; 26 (2S): 1–157. https://doi.org/10.14341/DM13042 (In Russ.)

3.Sloan G., Selvarajah D., Tesfaye S. Pathogenesis, Diagnosis and Clinical Management of Diabetic Sensorimotor Peripheral Neuropathy. Nat Rev Endocrinol. 2021; 17 (7): 400-420. https://doi.org/10.1038/s41574-021-00496-z

4.Tesfaye S., Boulton A.J.M., Dyck P.J., et al. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity and Treatments. Diabetes Care. 2010 Oct; 33 (10): 2285-2293. https://doi.org/10.2337/dc10-1303

5.Rayman G., Vas P., Dhatariya K., et al. The Ipswich Touch Test: a Simple and Novel Method to Identify Inpatients at Risk of Foot Ulceration. Diabetes Care. Diabetes Care. 2011 Jul; 34 (7):1517-1518. https://doi.org/10.2337/dc11-0156

6.Finnerup N.B., Kuner R., Jensen T.S. Neuropathic Pain: from Mechanisms to Treatment. Physiol Rev. 2021; 101 (1): 259-301. https://doi.org/10.1152/physrev.00045.2019

7.Pop-Busui R., Boulton A.J.M., Feldman E.L., et al. Diabetic Neuropathy: a Position Statement by the American Diabetes Association. Diabetes Care. 2017; 40 (1): 136–154. https://doi.org/10.2337/dc16-2042

8.Nogueira L.R.N., Silva A.A.O., Nogueira C.M. Behavior of Neuropathy Symptom Score in Early Diagnosis of Diabetic Polyneuropathy. Bodyw Mov Ther. 2024 Jan; 37: 76-82. https://doi.org/10.1016/j.jbmt.2023.11.030

9.Khramilin V.N., Strokov I.A., Davydov O.S., Churyukanov M.V. Diagnosis of Diabetic Polyneuropathy in Primary Care. Russian Journal of Pain. 2021; 19 (2): 47‑53. https://doi.org/10.17116/pain20211902147 (In Russ.)

10.Hsieh R.Y., et al. Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Sensorimotor Peripheral Neuropathy: a Meta-Analysis. Nutrients. 2023; 15 (16): 3634. https://doi.org/10.3390/nu15163634

11.Syed O., Jancic P., Knezevic N.N. A Review of Recent Pharmacological Advances in the Management of Diabetes-Associated Peripheral Neuropathy. Pharmaceuticals (Basel). 2023 May 29; 16 (6): 801. https://doi.org/10.3390/ph16060801

12.Zinovyeva O.E., Egorov P.D., Penkina A.I., Guseinov S.S. Ipidacrine Efficacy in Diabetic Polyneuropathy Complex Treatment: a Review. Consilium Medicum. 2022; 24 (2): 123–127. https://doi.org/10.26442/20751753.2022.2.201554

13.Kamchatnov P.R., Barantsevich E.R., Chugunov A.V., Kabanov A.A., Abusueva B.A. The Efficacy of Ipidacrine in Patients with Diabetic Polyneuropathy. Neurology, Neuropsychiatry, Psychosomatics. 2022;14 (3): 38–43. https://doi.org/10.14412/2074-2711-2022-3-38-43 (In Russ.)

14.Romeyko D.I. Bilodid I.K., Pukitas I.S. and others. The effectiveness of Neuromidin® in the Treatment of Diabetic Distal Polyneuropathy. Medical news. 2009. 6: 82-85 ( In Russ.)

15.Ziegler D., Hanefeld M., Ruhnau R.J. et al. The ALADIN III Study group. Treatment of Symptomatic Diabetic Peripherial Neuropathy with Antioxidant Alpha-Lipoic Acid. Diabetes Care 1999; 22: 1296-1230

16.Selvarajah D., Kar D., Khunti K., et al. Diabetic Peripheral Neuropathy: Advances in Diagnosis and Strategies for Screening and Early Intervention. Lancet Diabetes Endocrinol. 2019 Dec;7 (12): 938-948. https://doi.org/10.1016/S2213-8587(19)30081-6

17.Zangiabadi N., Shafiee K., Alavi KH., Assadi A.R., Damavandi M. Atorvastatin Treatment Improves Diabetic Polyneuropathy Electrophysiological Changes in Non-Insulin Dependent Diabetic Patients: A Double Blind, Randomized Clinical Trial. Minerva Endocrinol. 2012 Jun; 37 (2): 195-200

18.Yang H., Sloan G., Ye Y., et al. New Perspective in Diabetic Neuropathy: From the Periphery to the Brain, and Beyond. Front Endocrinol (Lausanne). 2020; 10: 929. https://doi.org/10.3389/fendo.2019.00929

19.Carmichael J., Fadavi H., Ishibashi F., et al. Advances in Screening, Early Diagnosis and Accurate Clinical Assessment of Diabetic Neuropathy. Front Endocrinol (Lausanne). 2021; 12: 671257. https://doi.org/10.3389/fendo.2021.671257

20.Gad H., Elgassim E., Mohammed I., et al. Continuous Glucose Monitoring Reveals A Novel Association Between Duration and Severity of Hypoglycemia, and Small Nerve Fiber Injury in Patients with Diabetes. Endocr Connect. 2022 Nov 14; 11(12): e220352. https://doi.org/10.1530/EC-22-0352

21. Yoo M., Sharma N., Pasnoor M., Kluding P.M. Painful Diabetic Peripheral Neuropathy: Presentations, Mechanisms, and Exercise Therapy. J Diabetes Metab. 2013 Jun 30; Suppl 10: 005. https://doi.org/10.4172/2155-6156.S10-005

22.Bril V., England J., Franklin G.M., et al. Evidence-based Guideline: Treatment of Painful Diabetic Neuropathy. Neurology. 2011 May 17; 76 (20): 1758-65. https://doi.org/10.1212/WNL.0b013e3182166ebe

23. Dworkin R.H., O’Connor A.B., Backonja M., et al. Pharmacologic Management of Neuropathic Pain: Evidence-Based Recommendations. Pain. 2007 Dec 5; 132 (3): 237-251. https://doi.org/10.1016/j.pain.2007.08.033

24.Yang J., Yang X., Zhao D., Wang X., Wei W., Yuan H. Association of Time in Range, as Assessed by Continuous Glucose Monitoring, with Painful Diabetic Polyneuropathy. J Diabetes Investig. 2021; 12(5): 828-836. https://doi.org/10.1111/jdi.13394

25.Callaghan B.C., Price R.S., Feldman E.L. Distal Symmetric Polyneuropathy: a Review. JAMA. 2020; 324 (13): 1392-1401. https://doi.org/10.1001/jama.2020.10245

26.Zhang X., Yang X., Sun B., Zhu C. Perspectives of Glycemic Variability in Diabetic Neuropathy: a Comprehensive Review. Commun Biol. 2021 Dec 7; 4 (1): 1366. https://doi.org/10.1038/s42003-021-02896-3

27.Hernández-Ojeda J., Román-Pintos L.M., Rodríguez-Carrízalez A.D., Troyo-Sanromán R., Cardona-Muñoz E.G., Alatorre-Carranza Mdel P., Miranda-Díaz A.G. Effect of Rosuvastatin on Diabetic Polyneuropathy: a Randomized, Double-Blind, Placebo-Controlled Phase Iia Study. Diabetes Metab Syndr Obes. 2014 Sep 4; 7: 401-407. https://doi.org/10.2147/DMSO.S65500

28.Yoo M., Sharma N., Pasnoor M., Kluding P.M. Painful Diabetic Peripheral Neuropathy: Presentations, Mechanisms, and Exercise Therapy. J Diabetes Metab. 2013 Jun 30; Suppl 10: 005. https://doi.org/10.4172/2155-6156.S10-005

29.Ametov A.S., Barinov A., Dyck P.J. et al. The sensory Symptoms of Diabetic Polyneuropathy are Improved with Alpha-Lipoic Acid. Diabetes Care 2003; 26: 770-776

30.Pop-Busui R., Boulton A.J., Feldman E.L., Bril V., Freeman R., Malik R.A., Sosenko J.M., Ziegler D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017 Jan; 40 (1): 136-154. https://doi.org/10.2337/dc16-2042

ADDITIONAL INFORMATION

Andrei P. Rachin, Dr. Sci. (Med.), Professor, President of the National Association of Experts in Comorbid Neurology, Moscow, Russia. E-mail: 7851377@gmail.com. ORCID: https://orcid.org/0000-0003-4266-0050

Sergei A. Rachin, Executive Director, National Association of Experts in Comorbid Neurology, Moscow, Russia. E-mail: Rachin.sergei@gmail.com. ORCID: https://orcid.org/0000-0001-9771-4621

Mikhail N. Sharov, Dr. Sci. (Med.), Professor, Professor of the Department of Therapy, Clinical Pharmacology and Emergency Medicine, Russian University of Medicine, Moscow, Russia. E-mail: 6112286@mail.ru. ORCID: https://orcid.org/0000-0001-9634-346X

Ruzanna R. Parsamyan, Ph.D. Sci. (Med.), Associate Professor of the Department of Neurology named after K.N. Tretyakova, Senior Researcher at the Department of Basic Research in Neurocardiology, Research Institute of Cardiology, Saratov State Medical University named after V.I. Razumovsky, Head of Clinic Pain, Saratov, Russia. E-mail: kvl.prr@mail.ru. ORCID: https://orcid.org/0000-0002-6509-5958

Sergey M. Karpov, Dr. Sci. (Med.), Professor, Head of the Department of Neurology, Neurosurgery and Medical Genetics Stavropol State Medical University, Stavropol, Russia. E-mail: karpov25@rambler.ru. ORCID: https://orcid.org/0000-0003-1472-6024

Author contributions. All authors confirm the compliance of their authorship, according to international ICMJE criteria (all authors made a significant contribution to the development of the concept, research and preparation of the article, read and approved the final version before publication).– searched for suitable literature;– correcting the text in accordance with the basic requirements. Special contributions: Rachin S.A., Karpov S.M., Parsamyan R.R. – formal analysis writing – review & editing; Rachin A.P., Sharov M.N.– conceptualization, methodology, investigation, data curation, writing – original draft.

Funding. This study was supported by external sources of funding.

Disclosure. The authors declare apparent or potential conflicts of interest related to the publication of this article. 

The content is available under the Creative Commons Attribution 4.0 License.

©2025. Andrei P. Rachin Sergei A. Rachin, Mikhail N. Sharov, Ruzanna R. Parsamyan, Sergei M. Karpov