Международный эндокринологический журнал Том 20, №7, 2024
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Вітамін В12 і діабетичні нейропатії
Авторы: Сергієнко В.О., Маркевич М.-Ю., Сегін В.Б., Сергієнко О.О.
Львівський національний медичний університет імені Данила Галицького, м. Львів, Україна
Рубрики: Эндокринология
Разделы: Справочник специалиста
Версия для печати
Вітамін B12 (ціанокобаламін, кобаламін) є необхідним кофактором двох важливих біохімічних шляхів: метаболізму метилмалонової кислоти та синтезу метіоніну з гомоцистеїну. Дефіцит кобаламіну, крім гематологічних аномалій (мегалобластної анемії або навіть панцитопенії), може викликати неврологічні симптоми, схожі на діабетичну нейропатію (ДН). Основні молекулярні механізми розвитку ДН все ще залишаються не з’ясованими. Більшість досліджень виявили внесок хронічного запалення низької інтенсивності (ХЗНІ) і оксидантного стресу (ОС) в розвиток ДН. Імуногістохімічні дослідження біоптатів нервів литкових м’язів, отриманих у хворих на цукровий діабет і ДН, вказують на активацію шляхів ХЗНІ, зумовлену підвищеним вмістом кінцевих продуктів неферментативного глікування, що призводить до посилення ОС. Подібні результати виявлені у пацієнтів з дефіцитом вітаміну В12. Отже, клінічні зміни у пацієнтів з ДН можуть бути спричинені клітинним дефіцитом кобаламіну. In vitro та in vivo продемонстровано, що вітамін B12 виявляє внутрішню антиоксидантну активність. Таким чином, кобаламін, незалежно від його класичної функції кофактора, може діяти як внутрішньоклітинний, зокрема як внутрішньомітохондріальний, антиоксидант. Це може слугувати обґрунтуванням для використання вітаміну B12 в лікуванні ДН, навіть на ранніх субклінічних стадіях. Метою цього огляду було обговорити роль вітаміну В12 у профілактиці та лікуванні ДН, а також проаналізувати нові тенденції та напрямки майбутніх досліджень. Пошук проводився в Scopus, Science Direct (від Elsevier) і PubMed, включно з базами даних Medline. Використані ключові слова «вітамін В12», «кобаламін», «цукровий діабет», «нейропатія», «кардіальна автономна нейропатія». Для виявлення результатів дослідження, які не вдалося знайти під час онлайн-пошуку, використовувався ручний пошук бібліографії публікацій.
Vitamin B12 (cyanocobalamin, cobalamin) is an essential cofactor in two important biochemical pathways: methylmalonic acid metabolism and methionine synthesis from homocysteine. In addition to hematologic abnormalities (megaloblastic anemia or even pancytopenia), cobalamin deficiency can cause neurologic symptoms similar to diabetic neuropathy (DN). The underlying molecular mechanisms of DN are still unclear. Most studies have identified the contribution of low-grade chronic inflammation (LGCI) and oxidative stress (OS) to the development of DN. Immunohistochemical studies of calf muscle nerve biopsies obtained from patients with diabetes mellitus and DN indicate activation of the LGCI pathway caused by increased levels of advanced glycation end products, which leads to increased OS. Similar results were found in patients with vitamin B12 deficiency. Thus, clinical changes in patients with DN may be caused by cellular cobalamin deficiency. In vitro and in vivo studies have demonstrated that vitamin B12 has intrinsic antioxidant activity. Thus, cobalamin, regardless of its classical function as a cofactor, can act as an intracellular, in particular intramitochondrial, antioxidant. This may serve as a rationale for the use of vitamin B12 in the treatment of DN, even in the early subclinical stages. The purpose of this review was to discuss the role of vitamin B12 in the prevention and treatment of DN, as well as to analyze new trends and directions for future research. The search was conducted in Scopus, Science Direct (from Elsevier) and PubMed, including MEDLINE databases. The keywords used were vitamin B12, cobalamin, diabetes mellitus, neuropathy, cardiac autonomic neuropathy. A manual search of the bibliography of publications was used to identify study results that could not be found during the online search.
вітамін В12; цукровий діабет; діабетична периферична нейропатія; кардіальна автономна нейропатія; огляд літератури
vitamin B12; diabetes mellitus; diabetic peripheral neuropathy; cardiac autonomic neuropathy; literature review
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- Halczuk K, Kaźmierczak-Barańska J, Karwowski BT, Karmańska A, Cieślak M. Vitamin B12-multifaceted in vivo functions and in vitro applications. Nutrients. 2023 Jun 13;15(12):2734. doi: 10.3390/nu15122734.
- Liu L, Huang X, Wang B, et al. Vitamin B12 and risk of diabetes: new insight from cross-sectional and longitudinal analyses of the China Stroke Primary Prevention Trial (CSPPT). BMJ Open Diabetes Res Care. 2020 Oct;8(1):e001423. doi: 10.1136/bmjdrc-2020-001423.
- Mathew AR, Di Matteo G, La Rosa P, et al. Vitamin B12 deficiency and the nervous system: beyond metabolic decompensation-comparing biological models and gaining new insights into molecular and cellular mechanisms. Int J Mol Sci. 2024 Jan 2;25(1):590. doi: 10.3390/ijms25010590.
- Gentile F, Bertini A, Priori A, Bocci T. Movement disorders and neuropathies: overlaps and mimics in clinical practice. J Neurol. 2022 Sep;269(9):4646-4662. doi: 10.1007/s00415-022-11200-0.
- Ghosh S, Castillo E, Frias ES, Swanson RA. Bioenergetic re–gulation of microglia. Glia. 2018 Jun;66(6):1200-1212. doi: 10.1002/glia.23271.
- Li W, Zhao J, Zhu LL, Peng YF. Serum vitamin B12 levels and glycemic fluctuation in patients with type 2 diabetes mellitus. Ther Adv Endocrinol Metab. 2022 Jun 1;13:20420188221102800. doi: 10.1177/20420188221102800.
- Batulwar PS, Anjankar A. Individuals diagnosed with type 2 diabetes mellitus and the status of vitamin B12 deficiency: A review. Cureus. 2024 Feb 27;16(2):e55103. doi: 10.7759/cureus.55103.
- Karedath J, Batool S, Arshad A, et al. The impact of vitamin B12 supplementation on clinical outcomes in patients with diabetic neuropathy: A meta-analysis of randomized controlled trials. Cureus. 2022 Nov 22;14(11):e31783. doi: 10.7759/cureus.31783.
- Bell DSH. Metformin-induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes. Diabetes Obes Metab. 2022 Aug;24(8):1423-1428. doi: 10.1111/dom.14734.
- Solomon LR. Functional cobalamin (vitamin B12) deficiency: role of advanced age and disorders associated with increased oxidative stress. Eur J Clin Nutr. 2015 Jun;69(6):687-692. doi: 10.1038/ejcn.2014.272.
- Madhu SV. Vitamin B12 and diabetes risk-myth or reality. Int J Diabetes Dev Ctries. 2020;40:1-3. doi: 10.1007/s13410-020-00810-x.
- Schleicher E, Didangelos T, Kotzakioulafi E, Cegan A, Peter A, Kantartzis K. Clinical pathobiochemistry of vitamin B12 deficiency: improving our understanding by exploring novel mechanisms with a focus on diabetic neuropathy. Nutrients. 2023 Jun 1;15(11):2597. doi: 10.3390/nu15112597.
- Vincenti A, Bertuzzo L, Limitone A, D’Antona G, Cena H. Perspective: practical approach to preventing subclinical B12 deficiency in elderly population. Nutrients. 2021 Jun 2;13(6):1913. doi: 10.3390/nu13061913.
- Lin Q, Li K, Chen Y, Xie J, Wu C, Cui C, Deng B. Oxidative stress in diabetic peripheral neuropathy: pathway and mechanism-based treatment. Mol Neurobiol. 2023 Aug;60(8):4574-4594. doi: 10.1007/s12035-023-03342-7.
- Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun 13;5(1):41. doi: 10.1038/s41572-019-0092-1.
- Nersesyan A, Mišík M, Cherkas A, et al. Use of micronucleus experiments for the detection of human cancer risks: A brief overview. Proc Shevchenko Sci Soc Med Sci. 2021;65(2):50-58. doi: 10.25040/ntsh2021.02.05.
- Feldman EL, Nave KA, Jensen TS, Bennett DLH. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain. Neuron. 2017 Mar 22;93(6):1296-1313. doi: 10.1016/j.neuron.2017.02.005.
- Serhiyenko VA, Serhiyenko AA. Diabetes mellitus and congestive heart failure. Miznarodnij Endokrinologicnij Zurnal (Ukraine). 2022;18(1):57-69. doi: 10.22141/2224-0721.18.1.2022.1146.
- Mukhtar M, Mohamed Y, Elbagir M, et al. Vitamin B12 status among patients with type 2 diabetes mellitus. Endocrinol Metab Clin. 2024 Mar 14;14(1):33-39. doi: https://doi.org/10.14740/jem928.
- Serhiyenko VA, Serhiyenko LM, Serhiyenko AA. Omega-3 polyunsaturated fatty acids in the treatment of diabetic cardiovascular autonomic neuropathy: A review. In: Moore SJ, ed. Omega-3: Dietary sources, biochemistry and impact on human health. New York: Nova Science Publishers, 2017. 79-154.
- Didangelos T, Karlafti E, Kotzakioulafi E, et al. Vitamin B12 supplementation in diabetic neuropathy: A 1-year, randomized, double-blind, placebo-controlled trial. Nutrients. 2021 Jan 27;13(2):395. doi: 10.3390/nu13020395.
- Okdahl T, Brock C. Molecular aspects in the potential of vitamins and supplements for treating diabetic neuropathy. Curr Diab Rep. 2021 Aug 27;21(9):31. doi: 10.1007/s11892-021-01397-1.
- Rakić M, Lunić T, Bekić M, et al. Vitamin B complex suppresses neuroinflammation in activated microglia: in vitro and in silico approach combined with dynamical modeling. Int Immunopharmacol. 2023 Aug;121:110525. doi: 10.1016/j.intimp.2023.110525.
- Pusceddu I, Herrmann W, Kleber ME, Scharnagl H, März W, Herrmann M. Telomere length, vitamin B12 and mortality in persons undergoing coronary angiography: the Ludwigshafen risk and cardiovascular health study. Aging (Albany NY). 2019 Sep 6;11(17):7083-7097. doi: 10.18632/aging.102238.
- Domínguez-López I, Kovatcheva M, Casas R, et al. Higher circulating vitamin B12 is associated with lower levels of inflammatory markers in individuals at high cardiovascular risk and in naturally aged mice. J Sci Food Agric. 2024 Jan 30;104(2):875-882. doi: 10.1002/jsfa.12976.
- Hirata T, Arai Y, Yuasa S, et al. Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages. Nat Commun. 2020 Jul 30;11(1):3820. doi: 10.1038/s41467-020-17636-0.
- Ortiz-Montero P, Londoño-Vallejo A, Vernot JP. Senescence-associated IL-6 and IL-8 cytokines induce a self- and cross-reinforced senescence/inflammatory milieu strengthening tumorigenic capabilities in the MCF-7 breast cancer cell line. Cell Commun Signal. 2017 May 4;15(1):17. doi: 10.1186/s12964-017-0172-3.
- Lee YJ, Wang MY, Lin MC, Lin PT. Associations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. Nutrients. 2016 Feb 26;8(3):118. doi: 10.3390/nu8030118.
- Homann L, Rentschler M, Brenner E, Böhm K, Röcken M, Wieder T. IFN-γ and TNF induce senescence and a distinct senescence-associated secretory phenotype in melanoma. Cells. 2022 Apr 30;11(9):1514. doi: 10.3390/cells11091514.
- Shen H, Campanello GC, Flicker D, et al. The human knoc–kout gene CLYBL connects itaconate to vitamin B12. Cell. 2017 Nov 2;171(4):771-782.e11. doi: 10.1016/j.cell.2017.09.051.
- Ruetz M, Campanello GC, Purchal M, et al. Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. Science. 2019 Nov 1;366(6465):589-593. doi: 10.1126/science.aay0934.
- Martucci M, Conte M, Bucci L, et al. Twelve-week daily consumption of ad hoc fortified milk with ω-3, D, and group B vitamins has a positive impact on inflammaging parameters: A randomized cross-over trial. Nutrients. 2020 Nov 22;12(11):3580. doi: 10.3390/nu12113580.
- Amer MS, Ali-Labib R, Farid TM, Rasheedy D, Tolba MF. Link between vitamin B12, type 2 diabetes mellitus, and bone mineral density in elderly patients. J. Clin. Gerontol. Geriatr. 2015; 6(4):120-124. doi: 10.1016/j.jcgg.2015.03.006.
- Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant strategies in the management of diabetic neuropathy. Biomed Res Int. 2015;2015:515042. doi: 10.1155/2015/515042.
- Sharebiani H, Mokaram M, Mirghani M, Fazeli B, Stanek A. The effects of antioxidant supplementation on the pathologic mechanisms of metabolic syndrome and cardiovascular disease development. Nutrients. 2024 May 27;16(11):1641. doi: 10.3390/nu16111641.
- Taira J. Oxidative stress modulators and functional foods. Antioxidants (Basel). 2021 Jan 29;10(2):191. doi: 10.3390/antiox10020191.
- Serhiyenko VA, Sehin VB, Pankiv VI, Serhiyenko AA. Post-traumatic stress disorder, dyssomnias, and metabolic syndrome. Miznarodnij Endokrinologicnij Zurnal (Ukraine). 2024 Mar;20(1):58-67. doi: 10.22141/2224-0721.20.1.2024.1359.
- Chan W, Almasieh M, Catrinescu MM, Levin LA. Cobalamin-associated superoxide scavenging in neuronal cells is a potential mechanism for vitamin B12-deprivation optic neuropathy. Am J Pathol. 2018 Jan;188(1):160-172. doi: 10.1016/j.ajpath.2017.08.032.
- van de Lagemaat EE, de Groot LCPGM, van den Heuvel EGHM. Vitamin B12 in relation to oxidative stress: A systematic review. Nutrients. 2019 Feb 25;11(2):482. doi: 10.3390/nu11020482.
- Wolffenbuttel BHR, Wouters HJCM, Heiner-Fokkema MR, van der Klauw MM. The many faces of cobalamin (vitamin B12) deficiency. Mayo Clin Proc Innov Qual Outcomes. 2019 May 27;3(2):200-214. doi: 10.1016/j.mayocpiqo.2019.03.002.
- Spataru T. The miracle of vitamin B12 biochemistry. Reactions. 2024;5(1):20-76. doi: 10.3390/reactions5010002.
- Gwathmey KG, Grogan J. Nutritional neuropathies. Muscle Nerve. 2020 Jul;62(1):13-29. doi: 10.1002/mus.26783.
- Rizzo G, Laganà AS, Rapisarda AM, et al. Vitamin B12 among vegetarians: status, assessment and supplementation. Nutrients. 2016 Nov 29;8(12):767. doi: 10.3390/nu8120767.
- Al Quran T, Khader A, Allan H, et al. Prevalence of vita–min B12 deficiency in type 2 diabetic patients taking metformin, a cross-sectional study in primary healthcare. Front Endocrinol (Lausanne). 2023 Sep 4;14:1226798. doi: 10.3389/fendo.2023.1226798.
- Allen LH, Miller JW, de Groot L, Rosenberg IH, Smith AD, Refsum H, Raiten DJ. Biomarkers of nutrition for development (BOND): Vitamin B-12 Review. J Nutr. 2018 Dec 1;148(suppl_4):1995S-2027S. doi: 10.1093/jn/nxy201.
- Rathis TS, Ranganathan RS, Solai Raja M, Srivastav PSS. Prevalence of vitamin B12 deficiency in type 2 diabetes mellitus patients on metformin therapy. Cureus. 2023 Apr 12;15(4):e37466. doi: 10.7759/cureus.37466.
- Alvarez M, Sierra OR, Saavedra G, Moreno S. Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study. Endocr Connect. 2019 Oct 1;8(10):1324-1329. doi: 10.1530/EC-19-0382.
- Hurley-Kim K, Vu CH, Dao NM, Tran LC, McBane S, Lee J, Sepassi A. Effect of metformin use on vitamin B12 deficiency over time (EMBER): A real-world evidence database study. Endocr Pract. 2023 Nov;29(11):862-867. doi: 10.1016/j.eprac.2023.06.013.
- Aroda VR, Edelstein SL, Goldberg RB, et al.; Diabetes Prevention Program Research Group. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016 Apr;101(4):1754-61. doi: 10.1210/jc.2015-3754.
- Farooq MD, Tak FA, Ara F, Rashid S, Mir IA. Vitamin B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes. J Xenobiot. 2022 May 31;12(2):122-130. doi: 10.3390/jox12020011.
- Didangelos T, Karlafti E, Kotzakioulafi E, Kontoninas Z, Margaritidis C, Giannoulaki P, Kantartzis K. Efficacy and safety of the combination of superoxide dismutase, alpha lipoic acid, vitamin B12, and carnitine for 12 months in patients with diabetic neuropathy. Nu–trients. 2020 Oct 23;12(11):3254. doi: 10.3390/nu12113254.
- 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 Oct;12(10):2631-2634. doi: 10.1007/s13300-021-01131-w.
- Rojbi I, Kalthoum M, Mekni S, Bouzid K, Khiari K, Ben Nacef I. Vitamin B12 levels in type 2 diabetic patients on metformin compared to those never on metformin: a cross sectional study in Tunisia. Tunis Med. 2023 Apr 5;101(4):433-439. PMID: 38372539; PMCID: PMC11217969.
- Yadav A, Jyoti S, Mehta RK, Parajuli SB. Vitamin B12 deficiency among metformin treated type 2 diabetic mellitus patients visiting the department of medicine of a tertiary care centre. JNMA J Nepal Med Assoc. 2023 Nov 1;61(267):861-863. doi: 10.31729/jnma.8340.
- Miller JW. Proton Pump inhibitors, H2-receptor antagonists, metformin, and Vitamin B-12 deficiency: clinical implications. Adv Nutr. 2018 Jul 1;9(4):511S-518S. doi: 10.1093/advances/nmy023.
- Pratama S, Lauren BC, Wisnu W. The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review. Diabetes Metab Syndr. 2022 Oct;16(10):102634. doi: 10.1016/j.dsx.2022.102634.
- Serhiyenko VA, Serhiyenko AA. Diabetes mellitus and arterial hypertension. Miznarodnij Endokrinologicnij Zurnal (Ukraine). 2021;17(2):100-113. doi: 0.22141/2224-0721.17.2.2021.230573.
- Wei J, Wei Y, Huang M, Wang P, Jia S. Is metformin a possible treatment for diabetic neuropathy? J Diabetes. 2022 Oct;14(10):658-669. doi: 10.1111/1753-0407.13310.
- Yang R, Yu H, Wu J, et al. Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing, China. Front Endocrinol (Lausanne). 2023 Feb 28;14:1082720. doi: 10.3389/fendo.2023.1082720.
- Arauz E, Cardoze D, Salehji A, Liguas A. Deficiencia de vitamina B12 relacionada al uso de metformina. Rev Méd Cient. 2020;33(1):52-63. doi: 10.37416/rmc.v33i1.585.
- Alharbi TJ, Tourkmani AM, Abdelhay O, et al. The association of metformin use with vitamin B12 deficiency and peripheral neuropathy in Saudi individuals with type 2 diabetes mellitus. PLoS One. 2018 Oct 15;13(10):e0204420. doi: 10.1371/journal.pone.0204420.
- Ahmed MA, Muntingh GL, Rheeder P. Perspectives on peri–pheral neuropathy as a consequence of metformin-induced vitamin B12 deficiency in T2DM. Int J Endocrinol. 2017;2017:2452853. doi: 10.1155/2017/2452853.
- Pankiv V. Influence of methylcobalamin on the vitamin B12 level and manifestations of neuropathy in patients with type 2 diabetes mellitus and metformin-associated vitamin B12 deficiency. Miznarodnij Endokrinologicnij Zurnal (Ukraine). 2019;15(4):317-321. doi: 10.22141/2224-0721.15.4.2019.174818.
- Serhiyenko VA, Serhiyenko LM, Sehin VB, Serhiyenko AA. Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy. Endocr Regul. 2021;55(4): 224-233. doi: 10.2478/enr-2021-0024.
- Delgado JA, Pastor García MI, Márquez Jiménez N, Costa Petit G, Regís Perelló A, Robles J, Bauça JM. Functional vitamin B12 deficiency: Improving methylmalonic acid reference intervals in urine. Clin Chim Acta. 2023 Apr 1;544:117334. doi: 10.1016/j.cca.2023.117334.
- Callaghan BC, Gallagher G, Fridman V, Feldman EL. Dia–betic neuropathy: what does the future hold? Diabetologia. 2020 May;63(5):891-897. doi: 10.1007/s00125-020-05085-9.
- Pang L, Lian X, Liu H, et al. Understanding diabetic neuropathy: focus on oxidative stress. Oxid Med Cell Longev. 2020 Jul 31;2020:9524635. doi: 10.1155/2020/9524635.
- Serhiyenko VA, Sehin VB, Serhiyenko LM, Serhiyenko AA. Post-traumatic stress disorder, metabolic syndrome, and chronic low-grade inflammation: A narrative review. Problemi Endocrinnoi Patologii. 2024 Mar 14;81(1):77-83. doi: 10.21856/j-PEP.2024.1.10.
- Rusli N, Ng CF, Makpol S, Wong YP, Mohd Isa IL, Remli R. Antioxidant effect in diabetic peripheral neuropathy in rat model: A systematic review. Antioxidants. 2024;13(9):1041. doi: 10.3390/antiox13091041.
- Thakur V, Sadanandan J, Chattopadhyay M. High-Mobility Group Box 1 Protein signaling in painful diabetic neuropathy. Int J Mol Sci. 2020 Jan 30;21(3):881. doi: 10.3390/ijms21030881.
- Ramasamy R, Shekhtman A, Schmidt AM. The RAGE/–DIAPH1 signaling axis & implications for the pathogenesis of diabetic complications. Int J Mol Sci. 2022 Apr 21;23(9):4579. doi: 10.3390/ijms23094579.
- Serhiyenko VA, Sehin VB, Serhiyenko LM, Serhiyenko AA. Post-traumatic stress disorder, metabolic syndrome, and the autono–mic nervous system. Endokrynologia. 2023 Dec;28(4):377-392. doi: 10.31793/1680-1466.2023.28-4.377.
- Arora K, Sequeira JM, Alarcon JM, Wasek B, Arning E, Bottiglieri T, Quadros EV. Neuropathology of vitamin B12 deficiency in the Cd320-/-mouse. FASEB J. 2019 Feb;33(2):2563-2573. doi: 10.1096/fj.201800754RR.
- Serhiyenko A, Baitsar M, Sehin V, Serhiyenko L, Kuznets V, Serhiyenko V. Post-traumatic stress disorder, insomnia, heart rate variability and metabolic syndrome (narrative review). Proc Shevchenko Sci Soc Med Sci. 2024 Jun;73(1):1-10. doi: 10.25040/ntsh2024.01.07.
- Wang X, Yang W, Zhu Y, Zhang S, Jiang M, Hu J, Zhang HH. Genomic DNA methylation in diabetic chronic complications in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne). 2022 Jun 29;13:896511. doi: 10.3389/fendo.2022.896511.
- Guo K, Eid SA, Elzinga SE, Pacut C, Feldman EL, Hur J. Genome-wide profiling of DNA methylation and gene expression identifies candidate genes for human diabetic neuropathy. Clin Epigenetics. 2020 Aug 12;12(1):123. doi: 10.1186/s13148-020-00913-6.
- Luciani A, Schumann A, Berquez M, et al. Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency. Nat Commun. 2020 Feb 20;11(1):970. doi: 10.1038/s41467-020-14729-8.
- Aguilar M, Alberti KGMM, Amiel SA, et al. Leitfaden zu typ-2-diabetes mellitus. Guide for type 2 diabetes mellitus (Review). Diabetes und Stoffwechsel. 2000 Mar 20;9(2):104-136.
- Serhiyenko VA, Serhiyenko AA. Diabetic cardiac autonomic neuropathy. In: Saldaña JR, editors. The Diabetes Textbook: Clinical Principles, Patient Management and Public Health Issues. Basel: Springer, Cham. Springer Nature Switzerland AG. 2023, Section 53. P. 939-966. doi: 10.1007/978-3-031-25519-9_57.
- Pop-Busui R Ang L, Boulton A, et al. Diagnosis and treatment of painful diabetic peripheral neuropathy. Compendia. 2022; 2022:1-32. doi: 10.2337/db2022-01.
- Hansen CS, Jensen JS, Ridderstråle M, Vistisen D, Jørgen–sen ME, Fleischer J. Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes. J Diabetes Complications. 2017 Jan;31(1):202-208. doi: 10.1016/j.jdiacomp.2016.08.025.
- Sakyi SA, Laing EF, Mantey R, et al. Profiling immuno-meta–bolic mediators of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in Ghana. PLoS One. 2021 Mar 30;16(3):e0249325. doi: 10.1371/journal.pone.0249325.
- Sereno MGB, Rezende HA, Caçador PS, Dornelas JPAP. Use of vitamin B12 in the treatment of diabetic neuropathy. Res Soc Dev. 2024;13(9):e1013946741. doi: 10.33448/rsd-v13i9.46741.
- Hannibal L, Lysne V, Bjørke-Monsen AL, et al. Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency. Front Mol Biosci. 2016 Jun 27;3:27. doi: 10.3389/fmolb.2016.00027.
- Jayabalan B, Low LL. Vitamin B supplementation for diabetic peripheral neuropathy. Singapore Med J. 2016 Feb;57(2):55-9. doi: 10.11622/smedj.2016027.
- Khan MRN, Umair M, Hussain W, et al. Exploring the relationship between vitamin b12 deficiency and diabetic neuropathy: a cross-sectional study investigating potential interventions. JPTCP. 2024;31(2):2224-2232. doi: 10.53555/jptcp.v31i2.4598.
- Hussain SIB, AlKhenizan A, Mahmoud A, Qashlaq H. The correlation between vitamin B12 and folate levels and bone mineral density among the Saudi population in a primary care setting. J Fa–mily Med Prim Care. 2023 Jun;12(6):1063-1068. doi: 10.4103/jfmpc.jfmpc_1209_22.
- Wee AKH, Sultana R. Determinants of vitamin B12 deficiency in patients with type-2 diabetes mellitus — A primary-care retrospective cohort study. BMC Prim Care. 2023 Apr 20;24(1):102. doi: 10.1186/s12875-023-02057-x.
- Longa López J, Dinamarca-Montecinos JL, Mejía-Rojas K, et al. Vitaminas B1, B6, B12 y neuropatías periféricas: Consenso de expertos. Rev Fac Med Hum. 2024;24(1):101-114. doi: 10.25176/RFMH.v24i1.6413.
- Wang D, Zhai JX, Liu DW. Serum folate, vitamin B12 le–vels and diabetic peripheral neuropathy in type 2 diabetes: A meta-ana–lysis. Mol Cell Endocrinol. 2017 Mar;443:72-79. doi: 10.1016/j.mce.2017.01.006.
- Satapathy S, Bandyopadhyay D, Patro BK, Khan S, Naik S. Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial. Complement Ther Med. 2020 Sep;53:102526. doi: 10.1016/j.ctim.2020.102526.
- Wakeman M, Archer DT. Metformin and micronutrient status in type 2 diabetes: does polypharmacy involving acid-suppressing medications affect vitamin B12 levels? Diabetes Metab Syndr Obes. 2020 Jun 18;13:2093-2108. doi: 10.2147/DMSO.S237454.