nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2021-5-116-122nnp-1675Research ArticleREVIEWSОБЗОРЫEvaluation and treatment of peripheral nervous system dysfunction in patients with prediabetesДиагностика и лечение поражений периферической нервной системы у пациентов с предиабетомЗиновьеваО. Е.ZinovyevaO. E.

Ольга Евгеньевна Зиновьева

Кафедра нервных болезней и нейрохирургии

119021, Москва, ул. Россолимо, 11, стр. 1

Olga Evgenyevna Zinovyeva

Department of Nervous System Diseases and Neurosurgery

11, Rossolimo St., Build. 1, Moscow 119021

zinovyevaolga@yandex.ruОстроумоваТ. М.OstroumovaT. M.

Кафедра нервных болезней и нейрохирургии

119021, Москва, ул. Россолимо, 11, стр. 1

Department of Nervous System Diseases and Neurosurgery

11, Rossolimo St., Build. 1, Moscow 119021

КоняшоваМ. В.KoniashovaM. V.

кафедра эндокринологии №1 Института клинической медицины им. Н.В. Склифосовского

119435, Москва, ул. Погодинская, 1, стр. 1

Department of Endocrinology №1, N.V. Sklifosovsky Institute of Clinical Medicine

1, Pogodinskaya St., Build. 1, Moscow 119435

ГорбачевН. А.GorbachevN. A.

Кафедра нервных болезней и нейрохирургии

119021, Москва, ул. Россолимо, 11, стр. 1

Department of Nervous System Diseases and Neurosurgery

11, Rossolimo St., Build. 1, Moscow 119021

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of RussiaRussian Federation202116102021135116122Copyright © Zinovyeva O.E., Ostroumova T.M., Koniashova M.V., Gorbachev N.A., 20212021Зиновьева О.Е., Остроумова Т.М., Коняшова М.В., Горбачев Н.А.Zinovyeva O.E., Ostroumova T.M., Koniashova M.V., Gorbachev N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/1675

The worldwide prevalence of prediabetes is steadily increasing, with up to a third of patients already showing signs of diabetic neuropathy (DN). Prediabetes includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or a combination of both.

Recent diagnostic criteria of prediabetes according to Russian, European, and American clinical guidelines are presented. The review covers the most common forms of DN in patients with prediabetes (distal symmetric sensory polyneuropathy, painful DN, cardiovascular autonomic neuropathy) and their prevalence. Recommended methods of DN screening are discussed: diagnostic scales, sensory testing, nerve conduction study, autonomic testing, corneal confocal microscopy. The results of studies evaluating instrumental methods for diagnosing peripheral nervous system (PNS) dysfunction in prediabetes are discussed. Management tactics in patients with prediabetes and PNS dysfunction should include non-pharmacological and pharmacological interventions. Combining a low-calorie diet and regular physical activity can delay the development of diabetes mellitus and reduce the severity of neuropathic pain. In patients with painful DN, the first-line therapy includes pregabalin, gabapentin, and duloxetine. Since there is no current data on the effect of hypoglycemic therapy on the risks of development and/or progression of DN in patients with prediabetes, antioxidants are considered pathogenetic therapy. Alpha-lipoic acid (Berlition®) in the management of patients with prediabetes is discussed.

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®).

предиабетдиабетическая невропатияпериферическая нервная системаальфа-липоевая кислотаprediabetesdiabetic neuropathyperipheral nervous systemalpha-lipoic acidReferencesШестакова 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: 10.26442/00403660.2019.10.000364Shestakova MV, Vikulova OK, Zheleznyakova AV, et al. Diabetes epidemiology in Russia: what has changed over the decade? Terapevticheskiy arkhiv = Therapeutic Archive. 2019;91(10):4-13. doi: 10.26442/00403660.2019.10.000364 (In Russ.).Дедов ИИ, Шестакова МВ, Майоров АЮ и др. Сахарный диабет 2 типа у взрослых. Сахарный диабет. 2020;23(2S):4-102. doi: 10.14341/DM12507Dedov II, Shestakova MV, Mayorov AYu, et al. Diabetes mellitus type 2 in adults. Sakharnyy diabet = Diabetes Mellitus. 2020;23(2S):4-102. doi: 10.14341/DM12507 (In Russ.).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/ehz486Cosentino 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/ehz486International Diabetes Federation. IDF Diabetes Atlas, 9 th ed. Brussels, Belgium: 2019. Available from: https://www.diabetesatlas.orgInternational Diabetes Federation. IDF Diabetes Atlas, 9 th ed. Brussels, Belgium: 2019. Available from: https://www.diabetesatlas.orgPfannkuche 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.2020.100053Pfannkuche 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.2020.100053Stino AM, Smith AG. Peripheral neuropathy in prediabetes and the metabolic syndrome. J Diabetes Investig. 2017 Sep;8(5):646-55. doi: 10.1111/jdi.12650Stino AM, Smith AG. Peripheral neuropathy in prediabetes and the metabolic syndrome. J Diabetes Investig. 2017 Sep;8(5):646-55. doi: 10.1111/jdi.12650Kirthi 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-2020-002040Kirthi 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-2020-002040American 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-S002American 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-S002Barrell K, Smith AG. Peripheral Neuropathy. Med Clin North Am. 2019 Mar;103(2):383-97. doi: 10.1016/j.mcna.2018.10.006Barrell K, Smith AG. Peripheral Neuropathy. Med Clin North Am. 2019 Mar;103(2):383-97. doi: 10.1016/j.mcna.2018.10.006Ziegler 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/dc07-1796Ziegler 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/dc07-1796Kazamel M, Stino AM, Smith AG. Metabolic syndrome and peripheral neuropathy. Muscle Nerve. 2021 Mar;63(3):285-93. doi: 10.1002/mus.27086Kazamel M, Stino AM, Smith AG. Metabolic syndrome and peripheral neuropathy. Muscle Nerve. 2021 Mar;63(3):285-93. doi: 10.1002/mus.27086Ziegler 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.xZiegler 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.xLee 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/dc14-2585Lee 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/dc14-2585Spallone 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.2018.0259Spallone 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.2018.0259Ziegler 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/s00125-015-3534-7Ziegler 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/s00125-015-3534-7Pop-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/dc16-2042Pop-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/dc16-2042Дедов 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/DM221S1Dedov II, Shestakova MV, Mayorov AYu, editors. Standards of specialized diabetes care: Clinical guidelines. 9 th ed. Sakharnyy diabet = Diabetes Mellitus. 2019;22(1S1):1-144 (In Russ.).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-S011American 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-S011Papanas N, Ziegler D. Prediabetic neuropathy: does it exist? Curr Diab Rep. 2012 Aug;12(4):376-83. doi: 10.1007/s11892-012-0278-3Papanas N, Ziegler D. Prediabetic neuropathy: does it exist? Curr Diab Rep. 2012 Aug;12(4):376-83. doi: 10.1007/s11892-012-0278-3Zeng 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.2018.01.031Zeng 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.2018.01.031Van 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/s00125-020-05194-5Van 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/s00125-020-05194-5Kopf 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.2018.10.020Kopf 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.2018.10.020Thaisetthawatkul 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.23891Thaisetthawatkul 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.23891McArthur JC. Painful small fiber neuropathies. Continuum (Minneap Minn). 2012 Feb;18(1):106-25. doi: 10.1212/01.CON.0000411570.79827.25McArthur JC. Painful small fiber neuropathies. Continuum (Minneap Minn). 2012 Feb;18(1):106-25. doi: 10.1212/01.CON.0000411570.79827.25Divisova 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.xDivisova 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.xAsghar 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/dc14-0279Asghar 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/dc14-0279DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011 Mar;37(3):588-98. doi: 10.1016/j.jcrs.2010.12.037DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011 Mar;37(3):588-98. doi: 10.1016/j.jcrs.2010.12.037Jende 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.2021.642589Jende 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.2021.642589Suo 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.00229.2016Suo 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.00229.2016Hinder 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.028530Hinder 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.028530Roncero-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.2019.02.027Roncero-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.2019.02.027Hemmingsen 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.pub4Hemmingsen 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.pub4Gong 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)30093-2Gong 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)30093-2Nathan 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)00291-0Nathan 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)00291-0Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006 Jun;29(6):1294-9. doi: 10.2337/dc06-0224Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006 Jun;29(6):1294-9. doi: 10.2337/dc06-0224Groover 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.2013.07.052Groover 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.2013.07.052Carnethon 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.dc05-1729Carnethon 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.dc05-1729Madsen 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.pub2Madsen 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.pub2Moelands 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.pub3Moelands 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.pub3Hemmingsen 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.pub2Hemmingsen 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.pub2Infante 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.i7.916Infante 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.i7.916Inzucchi 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/dc20-1675Inzucchi 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/dc20-1675Gabriel 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.0231196Gabriel 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.0231196Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun;5(1):41. doi: 10.1038/s41572-019-0092-1Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun;5(1):41. doi: 10.1038/s41572-019-0092-1Singh 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.2013.12.005Singh 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.2013.12.005Rahimlou 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.2019.03.015Rahimlou 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.2019.03.015Han 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-12-0555Han 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-12-0555Ziegler 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/dc11-0503Ziegler 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/dc11-0503Gosselin 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/c9fo00390hGosselin 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/c9fo00390hHaghighatdoost 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.2019.01.001Haghighatdoost 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

The authors declare that there are no conflicts of interest present.