The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Khramilin V.N.

Pirogov Russian National Research Medical University, Moscow, Russia

Gilemkhanova D.R.

Pirogov Russian National Research Medical University, Moscow, Russia

Lishchenko A.A.

Pirogov Russian National Research Medical University, Moscow, Russia

Combined polyneuropathies in diabetes mellitus: the role of toxic factors

Authors:

Khramilin V.N., Gilemkhanova D.R., Lishchenko A.A.

More about the authors

Read: 384 times


To cite this article:

Khramilin VN, Gilemkhanova DR, Lishchenko AA. Combined polyneuropathies in diabetes mellitus: the role of toxic factors. S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(3):13‑24. (In Russ.)
https://doi.org/10.17116/jnevro202612603113

References:

  1. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. https://doi.org/10.1016/j.diabres.2021.109119
  2. Bommer C, Sagalova V, Heesemann E, et al. Global Economic Burden of Diabetes in Adults: Projections From 2015 to 2030. Diabetes Care. 2018;41(5):963-970.  https://doi.org/10.2337/dc17-1962
  3. Parker ED, Lin J, Mahoney T, et al. Economic Costs of Diabetes in the U.S. in 2022. Diabetes Care. 2024;47(1):26-43.  https://doi.org/10.2337/dci23-0085
  4. Boulton AJM, Gries FA, Jervell JA. Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy. Diabet Med. 1998;15:508-514. 
  5. Mizokami-Stout KR, Li Z, Foster NC, et al. The Contemporary Prevalence of Diabetic Neuropathy in Type 1 Diabetes: Findings From the T1D Exchange. Diabetes Care. 2020;43(4):806-812.  https://doi.org/10.2337/dc19-1583
  6. Mizrak HI, Kufaishi H, Hecquet SK, et al. Contemporary prevalence of diabetic neuropathies in individuals with type 1 and type 2 diabetes in a Danish tertiary outpatient clinic. J Diabetes Complications. 2024;38(6):108761. https://doi.org/10.1016/j.jdiacomp.2024.108761
  7. Pop-Busui R, Boulton AJ, Feldman EL, 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. Braffett BH, El Ghormli L, Albers JW, et al. Neuropathic Pain With and Without Diabetic Peripheral Neuropathy in Type 1 Diabetes. Diabetes Care. 2024;47(9):1559-1567. https://doi.org/10.2337/dc23-1749
  9. Kerr M, Barron E, Chadwick P, et al. The cost of diabetic foot ulcers and amputations to the National Health Service in England. Diabet Med. 2019; 36(8):995-1002. https://doi.org/10.1111/dme.13973
  10. Pop-Busui R, Ang L, Boulton AJM, et al. Diagnosis and Treatment of Painful Diabetic Peripheral Neuropath. Arlington (VA): American Diabetes Association; 2022 Feb. 
  11. Callaghan BC, Cheng HT, Stables CL, et al. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521-534.  https://doi.org/10.1016/S1474-4422(12)70065-0
  12. Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):42.  https://doi.org/10.1038/s41572-019-0097-9
  13. Barbosa M, Saavedra A, Oliveira S, et al. Prevalence and Determinants of Painful and Painless Neuropathy in Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne). 2019;10:402.  https://doi.org/10.3389/fendo.2019.00402
  14. Davies M, Brophy S, Williams R, et al. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006;29(7):1518-1522. https://doi.org/10.2337/dc05-2228
  15. Van Hecke O, Austin SK, Khan RA, et al. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014; 155(4):654-662.  https://doi.org/10.1016/j.pain.2013.11.013
  16. Ziegler D, Landgraf R, Lobmann R, et al. Painful and painless neuropathies are distinct and largely undiagnosed entities in subjects participating in an educational initiative (PROTECT study). Diabetes Res Clin Pract. 2018;139:147-154.  https://doi.org/10.1016/j.diabres.2018.02.043
  17. Tesfaye S, Boulton AJM, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic care, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285-2293. https://doi.org/10.2337/dc10-1303
  18. Dyck PJ, Kratz KM, Karnes JL, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993;43:817-824. 
  19. Huizinga MM, Peltier A. Painful Diabetic Neuropathy: A Management-Centered Review. Clin Diabetes. 2007;25(1):6-15. 
  20. Gorson KC, Ropper AH. Additional causes for distal sensory polyneuropathy in diabetic patients. J Neurol Neurosurg Psychiatry. 2006;77:354-358. 
  21. Lozeron P, Nahum L, Lacroix C, et al. Symptomatic diabetic and non-diabetic neuropathies in a series of 100 diabetic patients. J Neurol. 2002; 249(5):69-575.  https://doi.org/10.1007/s004150200066
  22. Freeman R. Not all neuropathy in diabetes is of diabetic etiology: differential diagnosis of diabetic neuropathy. Curr Diab Rep. 2009;9(6):423-431.  https://doi.org/10.1007/s11892-009-0069-7
  23. Dedov II, Shestakova MV, Vikulova OK, et al. Atlas of the Russian Federation Diabetes Register. Status as of 2018. Diabetes Mellitus. 2019;22(2S):4-61. (In Russ.). https://doi.org/10.14341/DM12208
  24. Tesfaye S, Chaturvedi N, Eaton SE, et al. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005;352(4):41-350.  https://doi.org/10.1056/NEJMoa032782
  25. Baltrusch S. The Role of Neurotropic B Vitamins in Nerve Regeneration. Biomed Res Int. 2021;2021:9968228. https://doi.org/10.1155/2021/9968228
  26. Beulens JW, Kruidhof JS, Grobbee DE, et al. Alcohol consumption and risk of microvascular complications in type 1 diabetes patients: the EURODIAB Prospective Complications Study. Diabetologia. 2008;51:1631-1638. https://doi.org/10.1007/s00125-008-1091-z
  27. Harjutsalo V, Feodoroff M, Forsblom C, et al. Patients with Type 1 diabetes consuming alcoholic spirits have an increased risk of microvascular complications. Diabet Med. 2014;31(2):156-164.  https://doi.org/10.1111/dme.12307
  28. Khramilin VN, Demidova IYu, Ignatova OYu, Zenovko ME. Prevalence of diabetic polyneuropathy in newly diagnosed type 2 diabetes mellitus. Vrach. 2009;5:40-43. (In Russ.).
  29. Bell DS. Alcohol and the NIDDM patient. Diabetes Care. 1996;19:509-513.  https://doi.org/10.2337/diacare.19.5.509
  30. Tesfaye S, Boulton AJM, Dickenson AH. Mechanisms and management of diabetic painful distal symmetrical polyneuropathy. Diabetes Care. 2013; 36(9):2456-265.  https://doi.org/10.2337/dc12-1964
  31. Callaghan BC, Price RS, Feldman EL. Distal symmetric polyneuropathy: a review. JAMA. 2015;314(20):2172-2181. https://doi.org/10.1001/jama.2015.13611
  32. Lubec D, Müllbacher W, Finsterer J, et al. Diagnostic work-up in peripheral neuropathy: an analysis of 171 cases. Postgrad Med J. 1999;75(890):723-727.  https://doi.org/10.1136/pgmj.75.890.723
  33. England JD, Gronseth GS, Franklin G, et al. Practice parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing an evidence-based review). Neurology. 2009;72(2):185-192.  https://doi.org/10.1212/01.wnl.0000336370.51010.a1
  34. Ammendola A, Tata MR, Aurilio C, et al. Peripheral neuropathy in chronic alcoholism: a retrospective cross-sectional study in 76 subjects. Alcohol Alcohol. 2001;36(3):271-275. 
  35. Koike H, Mori K, Misu K, et al. Painful alcoholic polyneuropathy with predominant small-fiber loss and normal thiamine status. Neurology. 2001; 56:1727-1732. https://doi.org/10.1212/WNL.56.12.1727
  36. Koike H, Iijima M, Sugiura M, et al. Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Ann Neurol. 2003;54:19-29.  https://doi.org/10.1002/ana.10550
  37. Chandrasekaran K, Anjaneyulu M, Choi J. et al. Role of mitochondria in diabetic peripheral neuropathy: Influencing the NAD+-dependent SIRT1-PGC-1α-TFAM pathway. Int Rev Neurobiol. 2019;145:177-209.  https://doi.org/10.1016/bs.irn.2019.04.002
  38. Jankovic M, Novakovic I, Nikolic D, et al. Genetic and Epigenomic Modifiers of Diabetic Neuropathy. Int J Mol Sci. 2021;22(9):4887. https://doi.org/10.3390/ijms22094887
  39. Sachedina S, Toth C. Association of comorbidities with increasing severity of peripheral neuropathy in diabetes mellitus. World J Diabetes. 2013;4(4):135-144.  https://doi.org/10.4239/wjd.v4.i4.135
  40. Sempere-Bigorra M, Julián-Rochina I, Cauli O. Differences and Similarities in Neuropathy in Type 1 and 2 Diabetes: A Systematic Review. J Pers Med. 2021;11(3):230.  https://doi.org/10.3390/jpm11030230
  41. Johnson RH, Robinson BJ. Mortality in alcoholics with autonomic neuropathy. J Neurol Neurosurg Psychiatry. 1988;51:476-480. 
  42. Chopra K, Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol. 2012;73(3):348-362.  https://doi.org/10.1111/j.1365-2125.2011.04111.x
  43. Julian T, Glascow N, Syeed R, et al. Alcohol-related peripheral neuropathy: a systematic review and meta-analysis. J Neurol. 2019;266(12):2907-2919. https://doi.org/10.1007/s00415-018-9123-1
  44. Bell DSH, Goncalves E. Alcohol Consumption as a Causator and/or an Accelerator of Neuropathy in People With Diabetes Is Regularly Overlooked. Diabetes Ther. 2021;12(10):2631-2634. https://doi.org/10.1007/s13300-021-01131-w
  45. Peltier AC, Russell JW. Advances in understanding drug-induced neuropathies. Drug Saf. 2006;29:23-30. 
  46. Umapathi T, Chaudhry V. Toxic neuropathy. Curr Opin Neurol. 2005;18: 574-580. 
  47. Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. J Peripher Nerv Syst. 2008;13:27-46. 
  48. Gu J, Lu H, Chen C, et al. Diabetes mellitus as a risk factor for chemotherapy-induced peripheral neuropathy: a meta-analysis. Support Care Cancer. 2021;29(12):7461-7469. https://doi.org/10.1007/s00520-021-06321-7
  49. Smyth D, Kramarz C, Carr AS, et al. Toxic neuropathies: a practical approach. Pract Neurol. 2023;23(2):120-130.  https://doi.org/10.1136/pn-2022-003444
  50. Zeng L, Alongkronrusmee D, van Rijn RM. An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US. J Pain Res. 2017;10:219-228.  https://doi.org/10.2147/JPR.S125987
  51. Estofan LJF, Naydin S, Gliebus G. Quinolone-Induced Painful Peripheral Neuropathy: A Case Report and Literature Review. J Investig Med High Impact Case Rep. 2018;6:2324709617752736. https://doi.org/10.1177/2324709617752736
  52. Morales D, Pacurariu A, Slattery J, et al. Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy. JAMA Neurol. 2019;76(7):827-833.  https://doi.org/10.1001/jamaneurol.2019.0887
  53. Gaist D, Jeppesen U, Andersen M, et al. Statins and risk of polyneuropathy: a case-control study. Neurology. 2002;58(9):1333-1337. https://doi.org/10.1212/WNL.58.9.1333
  54. Lo YL, Leoh TH, Loh LM, et al. Statin therapy and small fibre neuropathy: a serial electrophysiological study. J Neurol Sci. 2003;208(1-2):105-108.  https://doi.org/10.1016/S0022-510X(02)00396-9
  55. Bhalla S, Singh N, Jaggi AS. Statins: do they aggravate or ameliorate neuropathic pain? J Pain. 2014;15(11):1069-1080. https://doi.org/10.1016/j.jpain.2014.06.012
  56. Pathak NN, Balaganur V, Lingaraju MC, et al. Atorvastatin attenuates neuropathic pain in rat neuropathy model by down-regulating oxidative damage at peripheral, spinal and supraspinal levels. Neurochem Int. 2014;68:1-9.  https://doi.org/10.1016/j.neuint.2014.01.014
  57. Hernandez-Ojeda J, Roman-Pintos LM, Rodriguez-Carrizalez AD, et al. Effect of rosuvastatin on diabetic polyneuropathy: a randomized, double-blind, placebo-controlled Phase IIA study. Diabetes Metab Syndr Obes. 2014;7:401-407.  https://doi.org/10.2147/DMSO.S65500
  58. Svendsen TK, Norregaard Hansen P, Garcia Rodriguez LA, et al. Statins and polyneuropathy revisited: case-control study in Denmark, 1999-2013. Br J Clin Pharmacol. 2017;83(9):2087-2095. https://doi.org/10.1111/bcp.13298
  59. Newman CB, Preiss D, Tobert JA, et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2019;39(2):e38-e81.  https://doi.org/10.1161/ATV.0000000000000073
  60. Pergolizzi JV Jr, Magnusson P, LeQuang JA, et al. Statins and Neuropathic Pain: A Narrative Review. Pain Ther. 2020;9(1):97-111.  https://doi.org/10.1007/s40122-020-00153-9
  61. Bressler AM, Zimmer SM, Gilmore JL, et al. Peripheral neuropathy associated with prolonged use of linezolid. Lancet Infect Dis. 2004;4:528-531. 
  62. Goolsby TA, Jakeman B, Gaynes RP. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature. Int J Antimicrob Agents. 2018;51(3):319-325.  https://doi.org/10.1016/j.ijantimicag.2017.08.033
  63. Yiannikas C, Pollard JD, McLeod JG. Nitrofurantoin neuropathy. Aust N Z J Med. 1981;11:400-405. 
  64. Pellissier JF, Pouget J, Cros D, et al. Peripheral neuropathy induced by amiodarone chlorhydrate. A clinicopathological study. J Neurol Sci. 1984; 63:251-266. 
  65. Boulton AJM, Vileikyte L. Painful Diabetic Neuropathy in Clinical Practice. 2011. https://doi.org/10.1007/978-0-85729-488-3_3
  66. Ziegler D, Keller J, Maier C, et al. DDG Praxisempfehlungen. Diabetische Neuropathie. Diabetologie. 2017;12(Suppl 2):S101-S114. (In German).
  67. Liampas A, Rekatsina M, Vadalouca A, et al. Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review. Pain Ther. 2021;10:55-68.  https://doi.org/10.1007/s40122-020-00210-3
  68. Ishii Y, Kojima J, Ikeda N, et al. Effect of NIK-247 on basal concentrations of extracellular acetylcholine in the cerebral cortex of conscious, freely moving rats. Jpn J Pharmacol. 1994;66(3):289-293.  https://doi.org/10.1254/jjp.66.289
  69. Kojima J, Onodera K. NIK-247 induces long-term potentiation of synaptic transmission in the CA1 region of rat hippocampal slices through M2 muscarinic receptors. Gen Pharmacol. 1998;31(2):297-300.  https://doi.org/10.1016/S0306-3623(97)00436-9
  70. Kojima J, Sugawara Y, Obara S. NIK-247 blocks voltage-dependent ionic currents in crayfish axon. Jpn J Pharmacol. 1991;57(4):545-552.  https://doi.org/10.1254/jjp.57.545
  71. Instructions for medical use of Neiromidin® (marketing authorization No. Π N014238/01-200122). (In Russ.).
  72. Kojima J, Onodera K. Effects of NIK-247 and tacrine on muscarinic receptor subtypes in rats. Gen Pharmacol. 1998;30(4):537-541.  https://doi.org/10.1016/S0306-3623(97)00303-0
  73. Kojima J, Onodera K, Ozeki M, et al. Ipidacrine (NIK-247): A Review of Multiple Mechanisms as an Antidementia Agent. CNS Drug Rev. 1998;4(3): 247-259.  https://doi.org/10.1111/j.1527-3458.1998.tb00067.x
  74. Lavretskaya E. Amiridine. A novel type of medicines-stimulants of the nervous and muscular system. Vneshtorgizdat; 1989. (In Russ.).
  75. Naser PV, Kuner R. Molecular, Cellular and Circuit Basis of Cholinergic Modulation of Pain. Neuroscience. 2018;387:135-148.  https://doi.org/10.1016/j.neuroscience.2017.08.049
  76. Ockenga W, Kühne S, Bocksberger S, et al. Non-Neuronal Functions of the M2 Muscarinic Acetylcholine Receptor. Genes. 2013;4:171-197. 
  77. Piovesana R, Reid AJ, Tata AM. Emerging Roles of Cholinergic Receptors in Schwann Cell Development and Plasticity. Biomedicines. 2023;11(1):41. 
  78. Golubovskaya OA, Shkurba AV, Tordiya DD. Correction of polyneuropathy in type 2 diabetes mellitus in patients with chronic hepatitis C. Clinical Infectology and Parasitology. 2013;1(04):141-150. (In Russ.).
  79. Dzyak LA, Shulga AN, Tsurkalenko ES. Efficacy of neuromidin in the treatment of diabetic polyneuropathy. Ukrainian Bulletin of Psychoneurology. 2007;15(2):135-138. (In Ukr.).
  80. Kamchatnov PR, Barantsevich ER, Chugunov AV, et al. Efficacy of ipidacrine in patients with diabetic polyneuropathy. Neurology, Neuropsychiatry, Psychosomatics. 2022;14(3):38-43. (In Russ.).
  81. Levin OS, Matvievskaya OV. Epidemiological assessment of the impact of Ipigrix® therapy on motor and sensory functions in outpatients with peripheral nervous system disorders (results of the observational IMPULSE study). Medical Alphabet. 2019;1(2):11-14. (In Russ.).
  82. Malkov AB. Prospective evaluation of the effectiveness of various methods to prevent progression of subclinical diabetic distal neuropathy. Meditsinskie novosti. 2018;7(286):61-67. (In Russ.).
  83. Pashkovskaya NV, Pashkovsky VM, Zoriy IA. Efficacy of Neuromidin® in the treatment of diabetic distal symmetric polyneuropathy. International Endocrinology Journal. 2019;15(3):230-235. (In Russ.). https://doi.org/10.22141/2224-0721.15.3.2019.172109
  84. Rachin AP, Sharov MN, Rachin SA, et al. Observational study evaluating the efficacy of Ipigrix in diabetic polyneuropathy (NIRVANA study). Nervous Diseases. 2018;2:26-31. (In Russ.).
  85. Romeiko DI, Bilodid IK, Pukita IS, et al. Efficacy of Neuromidin® in the treatment of diabetic distal polyneuropathy. Meditsinskie novosti. 2009; 6:82-85. (In Russ.).
  86. Samartsev IN, Zhivolupov SA, Markova MV, et al. Open-label observational study of the efficacy and tolerability of ipidacrine in patients with diabetic polyneuropathy (DIAMANT study). Neurology and Psychiatry. 2024;(2):26-32. (In Russ.). https://doi.org/10.33667/2078-5631-2024-2-26-32
  87. Strokov IA, Zinovieva OE, Akhmedzhanova LT, et al. Activation of regeneration and reinnervation processes in diabetic polyneuropathy. Doctor.Ru. 2008;4(41):16-22. (In Russ.).
  88. Fedin AI, Solovyova EYu. Effects of Ipigrix on motor, sensory, and cognitive functions in patients with peripheral and central nervous system diseases in real-world clinical practice: results of a multicenter observational study. Medical Alphabet. 2018;2(17(354)):9-12. (In Russ.).
  89. Khramilin VN, Davydov OS, Yakhno NN, et al. Diagnostic and treatment algorithm for patients with diabetic polyneuropathy. Expert Council resolution (March 01, 2025). S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(8):102-113. (In Russ.). https://doi.org/10.17116/jnevro2025125081102

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.