Диагностика и лечение поражений периферической нервной системы у пациентов с предиабетом

Распространенность предиабета в мире неуклонно увеличивается, при этом до трети пациентов уже имеют признаки диабетической невропатии (ДНП). Под предиабетом подразумевают наличие у пациента нарушенной гликемии натощак (НГН), нарушенной толерантности к глюкозе (НТГ) либо их сочетания. Представлены современные критерии диагностики предиабета согласно российским, европейским и американским клиническим рекомендациям. В обзоре рассмотрены наиболее частые формы ДНП у пациентов с предиабетом (дистальная симметричная сенсорная полиневропатия, болевая ДНП, кардиваскулярная автономная невропатия), а также их распространенность. Приведены рекомендуемые методы скрининга ДНП: диагностические шкалы, исследование чувствительности, электронейромиография, вегетативное тестирование, конфокальная микроскопия роговицы. Обсуждаются результаты исследований, посвященных инструментальным методам диагностики поражения периферической нервной системы (ПНС) в случаях предиабета. Рассмотрена тактика ведения пациентов с предиабетом с поражением ПНС, которая должна включать немедикаментозные и медикаментозные методы. Комбинация низкокалорийной диеты и регулярной физической активности позволяет отсрочить развитие сахарного диабета 2-го типа и уменьшить выраженность невропатической боли. При наличии болевой формы ДНП препаратами первой линии являются прегабалин, габапентин и дулоксетин. Поскольку в настоящее время нет данных о влиянии сахароснижающей терапии на риски развития и/или прогрессирования ДНП у пациентов с предиабетом, в качестве патогенетической терапии рассматриваются препараты из группы антиоксидантов. Обсуждается использование при ведении пациентов с предиабетом препаратов альфа-липоевой кислоты (Берлитион^®).

1. Шестакова МВ, Викулова ОК, Железнякова АВ и др. Эпидемиология сахарного диабета в Российской Федерации: что изменилось за последнее десятилетие? Терапевтический архив. 2019;91(10):4-13. doi: 10.26442/00403660.2019.10.000364

2. Дедов ИИ, Шестакова МВ, Майоров АЮ и др. Сахарный диабет 2 типа у взрослых. Сахарный диабет. 2020;23(2S):4-102. doi: 10.14341/DM12507

3. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020 Jan 7;41(2):255-323. doi: 10.1093/eurheartj/ehz486

4. International Diabetes Federation. IDF Diabetes Atlas, 9 th ed. Brussels, Belgium: 2019. Available from: https://www.diabetesatlas.org

5. Pfannkuche A, Alhajjar A, Ming A, et al. Prevalence and risk factors of diabetic peripheral neuropathy in a diabetics cohort: Register initiative «diabetes and nerves». Endocr Metab Sci. 2020 Jul;1(1-2):100053. doi: 10.1016/j.endmts.2020.100053

6. Stino AM, Smith AG. Peripheral neuropathy in prediabetes and the metabolic syndrome. J Diabetes Investig. 2017 Sep;8(5):646-55. doi: 10.1111/jdi.12650

7. Kirthi V, Perumbalath A, Brown E, et al. Prevalence of peripheral neuropathy in pre-diabetes: a systematic review. BMJ Open Diabetes Res Care. 2021 May;9(1):e002040. doi: 10.1136/bmjdrc-2020-002040

8. American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes – 2021. Diabetes Care. 2021 Jan;44(Suppl. 1):S15-S33. doi: 10.2337/dc21-S002

9. Barrell K, Smith AG. Peripheral Neuropathy. Med Clin North Am. 2019 Mar;103(2):383-97. doi: 10.1016/j.mcna.2018.10.006

10. Ziegler D, Rathmann W, Dickhaus T, et al. Prevalence of polyneuropathy in pre-diabetes and diabetes is associated with abdominal obesity and macroangiopathy: the MONICA/KORA Augsburg Surveys S2 and S3. Diabetes Care. 2008 Mar;31(3):464-9. doi: 10.2337/dc07-1796

11. Kazamel M, Stino AM, Smith AG. Metabolic syndrome and peripheral neuropathy. Muscle Nerve. 2021 Mar;63(3):285-93. doi: 10.1002/mus.27086

12. Ziegler D, Rathmann W, Dickhaus T, et al. Neuropathic pain in diabetes, prediabetes and normal glucose tolerance: the MONICA/KORA Augsburg Surveys S2 and S3. Pain Med. 2009 Mar;10(2):393-400. doi: 10.1111/j.1526-4637.2008.00555.x

13. Lee CC, Perkins BA, Kayaniyil S, et al. Peripheral Neuropathy and Nerve Dysfunction in Individuals at High Risk for Type 2 Diabetes: The PROMISE Cohort. Diabetes Care. 2015 May;38(5):793-800. doi: 10.2337/dc14-2585

14. Spallone V. Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet. Diabetes Metab J. 2019 Feb;43(1):3-30. doi: 10.4093/dmj.2018.0259

15. Ziegler D, Voss A, Rathmann W, et al. Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey. Diabetologia. 2015 May;58(5):1118-28. doi: 10.1007/s00125-015-3534-7

16. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40:136-54. doi: 10.2337/dc16-2042

17. Дедов ИИ, Шестакова МВ, Майоров АЮ, редакторы. Алгоритмы специализированной медицинской помощи больным сахарным диабетом: Клинические рекомендации. 9-й выпуск. Сахарный диабет. 2019;22(1S1):1-144. doi: 10.14341/DM221S1

18. American Diabetes Association. Microvascular complications and foot care: Standards of Medical Care in Diabetes – 2021. Diabetes Care. 2021 Jan;44(Suppl. 1):S151-S167. doi: 10.2337/dc21-S011

19. Papanas N, Ziegler D. Prediabetic neuropathy: does it exist? Curr Diab Rep. 2012 Aug;12(4):376-83. doi: 10.1007/s11892-012-0278-3

20. Zeng J, Xu Y, Shi Y, Jiang C. Inflammation role in sensory neuropathy in Chinese patients with diabetes/prediabetes. Clin Neurol Neurosurg. 2018 Mar;166:136-40. doi: 10.1016/j.clineuro.2018.01.031

21. Van der Velde JHPM, Koster A, Strotmeyer ES, et al. Cardiometabolic risk factors as determinants of peripheral nerve function: the Maastricht Study. Diabetologia. 2020 Aug;63(8):1648-58. doi: 10.1007/s00125-020-05194-5

22. Kopf S, Groener JB, Kender Z, et al. Deep phenotyping neuropathy: An underestimated complication in patients with pre-diabetes and type 2 diabetes associated with albuminuria. Diabetes Res Clin Pract. 2018 Dec;146:191-201. doi: 10.1016/j.diabres.2018.10.020

23. Thaisetthawatkul P, Fernandes Filho JA, Herrmann DN. Contribution of QSART to the diagnosis of small fiber neuropathy. Muscle Nerve. 2013 Dec;48(6):883-8. doi: 10.1002/mus.23891

24. McArthur JC. Painful small fiber neuropathies. Continuum (Minneap Minn). 2012 Feb;18(1):106-25. doi: 10.1212/01.CON.0000411570.79827.25

25. Divisova S, Vlckova E, Hnojcikova M, et al. Prediabetes/early diabetes-associated neuropathy predominantly involves sensory small fibres. J Peripher Nerv Syst. 2012 Sep;17(3):341-50. doi: 10.1111/j.1529-8027.2012.00420.x

26. Asghar O, Petropoulos IN, Alam U, et al. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014 Sep;37(9):2643-6. doi: 10.2337/dc14-0279

27. DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011 Mar;37(3):588-98. doi: 10.1016/j.jcrs.2010.12.037

28. Jende JME, Kender Z, Mooshage C, et al. Diffusion Tensor Imaging of the Sciatic Nerve as a Surrogate Marker for Nerve Functionality of the Upper and Lower Limb in Patients With Diabetes and Prediabetes. Front Neurosci. 2021 Mar;15:642589. doi: 10.3389/fnins.2021.642589

29. Suo M, Wang P, Zhang M. Role of Fyn-mediated NMDA receptor function in prediabetic neuropathy in mice. J Neurophysiol. 2016 Aug;116(2):448-55. doi: 10.1152/jn.00229.2016

30. Hinder LM, O'Brien PD, Hayes JM, et al. Dietary reversal of neuropathy in a murine model of prediabetes and metabolic syndrome. Dis Model Mech. 2017 Jun;10(6):717-25. doi: 10.1242/dmm.028530

31. Roncero-Ramos I, Alcala-Diaz JF, Rangel-Zuniga OA, et al. Prediabetes diagnosis criteria, type 2 diabetes risk and dietary modulation: The CORDIOPREV study. Clin Nutr. 2020 Feb;39(2):492-500. doi: 10.1016/j.clnu.2019.02.027

32. Hemmingsen B, Gimenez-Perez G, Mauricio D, et al. Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus. Cochrane Database Syst Rev. 2017 Dec 4;12(12):CD003054. doi: 10.1002/14651858.CD003054.pub4

33. Gong Q, Zhang P, Wang J, et al. Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30year results of the Da Qing Diabetes Prevention Outcome Study. Lancet Diabetes Endocrinol. 2019 Jun;7(6):452-61. doi: 10.1016/S2213-8587(19)30093-2

34. Nathan DM, Barrett-Connor E, Crandall JP, et al. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-75. doi: 10.1016/S2213-8587(15)00291-0

35. Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006 Jun;29(6):1294-9. doi: 10.2337/dc06-0224

36. Groover AL, Ryals JM, Guilford BL, et al. Exercise-mediated improvements in painful neuropathy associated with prediabetes in mice. Pain. 2013 Dec;154(12):2658-67. doi: 10.1016/j.pain.2013.07.052

37. Carnethon MR, Prineas RJ, Temprosa M, et al. The association among autonomic nervous system function, incident diabetes, and intervention arm in the Diabetes Prevention Program. Diabetes Care. 2006 Apr;29(4):914-9. doi: 10.2337/diacare.29.04.06.dc05-1729

38. Madsen KS, Chi Y, Metzendorf MI, et al. Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2019 Dec;12(12):CD008558. doi: 10.1002/14651858.CD008558.pub2

39. Moelands SV, Lucassen PL, Akkermans RP, et al. Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus. Cochrane Database Syst Rev. 2018 Dec;12(12):CD005061. doi: 10.1002/14651858.CD005061.pub3

40. Hemmingsen B, Sonne DP, Metzendorf MI, Richter B. Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2017 May;5(5):CD012204. doi: 10.1002/14651858.CD012204.pub2

41. Infante M, Leoni M, Caprio M, Fabbri A. Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind. World J Diabetes. 2021 Jul;12(7):916-31. doi: 10.4239/wjd.v12.i7.916

42. Inzucchi SE, Docherty KF, Kњber L, et al. Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF. Diabetes Care. 2021 Feb;44(2):586-94. doi: 10.2337/dc20-1675

43. Gabriel R, Boukichou Abdelkader N, Acosta T, et al. Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data. PLoS One. 2020 Apr;15(4):e0231196. doi: 10.1371/journal.pone.0231196

44. Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun;5(1):41. doi: 10.1038/s41572-019-0092-1

45. Singh R, Kishore L, Kaur N. Diabetic peripheral neuropathy: current perspective and future directions. Pharmacol Res. 2014 Feb;80:21-35. doi: 10.1016/j.phrs.2013.12.005

46. Rahimlou M, Asadi M, Banaei Jahromi N, Mansoori A. Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta-analysis. Clin Nutr ESPEN. 2019 Aug;32:16-28. doi: 10.1016/j.clnesp.2019.03.015

47. Han T, Bai J, Liu W, Hu Y. A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur J Endocrinol. 2012 Oct;167(4):465-71. doi: 10.1530/EJE-12-0555

48. Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 year in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011 Sep;34(9):2054-60. doi: 10.2337/dc11-0503

49. Gosselin LE, Chrapowitzky L, Rideout TC. Metabolic effects of α-lipoic acid supplementation in pre-diabetics: a randomized, placebo-controlled pilot study. Food Funct. 2019 Sep;10(9):5732-8. doi: 10.1039/c9fo00390h

50. Haghighatdoost F, Hariri M. Does alpha-lipoic acid affect lipid profile? A meta-analysis and systematic review on randomized controlled trials. Eur J Pharmacol. 2019 Mar;847:1-10. doi: 10.1016/j.ejphar.2019.01.001