Association between B-Vitamin Homeostasis and Gestational Diabetes Mellitus

doi:10.12280/gjfckx.20251470

Abstract

Abstract:

The homeostasis of B-vitamin is crucial for normal fetal development and maternal health. Studies have found that appropriate supplementation of B-vitamin may contribute to the prevention and management of gestational diabetes mellitus (GDM). GDM is one of the most common metabolic diseases during pregnancy and can exert short-term or long-term adverse effects on the health of both the patient and her offspring. Through a systematic review of relevant domestic and international research, this article explores the association between B-vitamin and GDM, aiming to provide evidence for the scientific supplementation of B-vitamin in clinical practice. Folate (vitamin B₉) is an essential micronutrient for one-carbon metabolism. Recent studies have found that serum or erythrocyte folate levels are positively correlated with the risk of GDM, and the risk of developing GDM increases significantly when folate supplement intake exceeds recommended levels. Vitamin B₁₂ is closely related to folate, and an imbalance in their ratio may also be a risk factor of GDM. Vitamins B₁, B₂, B₃, and B₆, as key coenzymes or regulators of energy metabolism, also exhibit varying degrees of association between their intake levels and the risk of GDM. An imbalance in B-vitamin nutritional status during pregnancy may increase the risk of GDM, suggesting that appropriate doses of these micronutrients should be supplemented during pregnancy to safeguard maternal and child health.

Key words: Vitamin B complex, Diabetes, gestational, Insulin resistance, Glucose metabolism disorders, B-vitamin homeostasis

SHEN Cheng-lu, HU Wen-sheng. Association between B-Vitamin Homeostasis and Gestational Diabetes Mellitus[J]. Journal of International Obstetrics and Gynecology, 2026, 53(2): 153-158.

References 39

[1]	Ye W, Luo C, Huang J, et al. Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis[J]. BMJ, 2022, 377:e067946. doi: 10.1136/bmj-2021-067946.
[2]	王晨, 杨慧霞. 重视妊娠合并内分泌代谢性疾病的诊治[J]. 实用妇产科杂志, 2023, 39(5):321-323. doi: 10.3969/j.issn.1003-6946.2023.5.syfckzz202305001.
[3]	Yang Q, Yang Y, Nie G, et al. The impact of mobile health interventions on maternal-neonatal outcomes in women with gestational diabetes mellitus: a systematic review and meta-analysis[J]. Front Endocrinol(Lausanne), 2025, 16:1707520. doi: 10.3389/fendo.2025.1707520.
[4]	Frost Z, Bakhit S, Amaefuna CN, et al. Recent Advances on the Role of B Vitamins in Cancer Prevention and Progression[J]. Int J Mol Sci, 2025, 26(5):1967. doi: 10.3390/ijms26051967.
[5]	De Zanetti L, Van Der Straeten D. 'From metabolism to metabolism': holistic considerations on B-vitamin interactions, biofortification, and deficiencies[J]. Curr Opin Biotechnol, 2024, 87:103132. doi: 10.1016/j.copbio.2024.103132.
[6]	Liu Z, Farkas P, Wang K, et al. B vitamin supply in plants and humans: the importance of vitamer homeostasis[J]. Plant J, 2022, 111(3):662-682. doi: 10.1111/tpj.15859.
[7]	Shelp GV, Dong J, Orlov NO, et al. Exposure to prenatal excess or imbalanced micronutrients leads to long-term perturbations in one-carbon metabolism, trimethylamine-N-oxide and DNA methylation in Wistar rat offspring[J]. FASEB J, 2024, 38(16):e70032. doi: 10.1096/fj.202401018RR.
[8]	Barry MJ, Nicholson WK, Silverstein M, et al. Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement[J]. JAMA, 2023, 330(5):454-459. doi: 10.1001/jama.2023.12876. pmid: 37526713
[9]	Van Vliet MM, Schoenmakers S, Willemsen SP, et al. First Trimester Maternal Folate and Vitamin B12 Concentrations and Their Associations With First-Trimester Placental Growth: The Rotterdam Periconception Cohort[J]. Obstet Gynecol Surv, 2025, 80(11):704-706. doi: 10.1097/OGX.0000000000001461.
[10]	Xu Z, Li Y, Liu Y, et al. Diverse associations observed between pregnancy complications and RBC or plasma folates determined by an in-house developed LC-MS/MS method[J]. Ann Med, 2023, 55(2):2265381. doi: 10.1080/07853890.2023.2265381.
[11]	Mussai EX, Lofft ZA, Vanderkruk B, et al. Folic acid supplementation in a mouse model of diabetes in pregnancy alters insulin sensitivity in female mice and beta cell mass in offspring[J]. FASEB J, 2023, 37(11):e23200. doi: 10.1096/fj.202301491R.
[12]	Xu R, Liu S, Zhong Z, et al. The Influence of Maternal Folate Status on Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis[J]. Nutrients, 2023, 15(12):2766. doi: 10.3390/nu15122766.
[13]	Zheng W, Zhang Y, Zhang P, et al. Gestational diabetes mellitus is associated with distinct folate-related metabolites in early and mid-pregnancy: A prospective cohort study[J]. Diabetes Metab Res Rev, 2024, 40(4):e3814. doi: 10.1002/dmrr.3814.
[14]	Chen X, Zhang Y, Chen H, et al. Association of Maternal Folate and Vitamin B₁₂ in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study[J]. Diabetes Care, 2021, 44(1):217-223. doi: 10.2337/dc20-1607.
[15]	Li N, Jiang J, Guo L. Effects of maternal folate and vitamin B12 on gestational diabetes mellitus: a dose-response meta-analysis of observational studies[J]. Eur J Clin Nutr, 2022, 76(11):1502-1512. doi: 10.1038/s41430-022-01076-8. pmid: 35105943
[16]	Zhu L, Zhou Y, Fu Y, et al. Association of Folic Acid Supplementation, Dietary Folate Intake and Serum Folate Levels with Risk of Gestational Diabetes Mellitus: A Matched Case-Control Study[J]. J Nutr Sci Vitaminol(Tokyo), 2023, 69(1):28-37. doi: 10.3177/jnsv.69.28.
[17]	Zou J, Fu Q, Huang X, et al. U-shaped Association Between Folic Acid Supplementation and the Risk of Gestational Diabetes Mellitus in Chinese Women[J]. Can J Diabetes, 2023, 47(1):78-84. doi: 10.1016/j.jcjd.2022.10.007.
[18]	Gómez-Cabrera AS, González-Santiago AE, Castañeda-Arellano R, et al. Folic Acid Supplementation and Risk of Gestational Diabetes Mellitus: A Systematic Review of the Literature[J]. Int J Mol Sci, 2025, 26(16):7977. doi: 10.3390/ijms26167977.
[19]	Williamson JM, Arthurs AL, Smith MD, et al. High Folate, Perturbed One-Carbon Metabolism and Gestational Diabetes Mellitus[J]. Nutrients, 2022, 14(19):3930. doi: 10.3390/nu14193930.
[20]	Wang H, Du Z, Ding X, et al. The association between visceral fat accumulation caused by high-dose folic acid supplementation in the first trimester and gestational diabetes mellitus: protocol for a nested case-control study in a cohort study[J]. BMC Pregnancy Childbirth, 2025, 25(1):1126. doi: 10.1186/s12884-025-08174-y.
[21]	Wang N, Zhou T, Ma X, et al. The Association between Maternal B Vitamins in Early Pregnancy and Gestational Diabetes Mellitus: A Prospective Cohort Study[J]. Nutrients, 2022, 14(23):5016. doi: 10.3390/nu14235016.
[22]	Xu Y, Zhu S, Song H, et al. A new modified obstetric early warning score for prognostication of severe maternal morbidity[J]. BMC Pregnancy Childbirth, 2022, 22(1):901. doi: 10.1186/s12884-022-05216-7.
[23]	Chen X, Du Y, Xia S, et al. Vitamin B₁₂ and gestational diabetes mellitus: a systematic review and meta-analysis[J]. Br J Nutr, 2022 Aug 2:1-8. doi: 10.1017/S000711452200246X.Epubaheadofprint.
[24]	Cheng Y, Lu X, Zhao F, et al. The Effects of Serum Folic Acid and Vitamin B12 on the Risk of Gestational Diabetes Mellitus[J]. Diabetes Metab Syndr Obes, 2022, 15:3891-3899. doi: 10.2147/DMSO.S391888.
[25]	Wu X, Zhang R, Lu L, et al. Association between dietary folate intake and gestational diabetes mellitus: evidence from baseline data of a Chinese maternal and infant cohort[J]. Front Nutr, 2025, 12:1702918. doi: 10.3389/fnut.2025.1702918.
[26]	Liu X, Zeng X, Wang J, et al. Associations of maternal serum folate, vitamin B12 and their imbalance with gestational diabetes mellitus: The mediation effects of the methionine cycle related metabolites[J]. Clin Nutr, 2025, 48:50-59. doi: 10.1016/j.clnu.2025.03.009. pmid: 40154196
[27]	Su J, Cai C, Zhang Y, et al. The role of folic acid and vitamin B12 in gestational diabetes mellitus and offspring development: A narrative review[J]. J Nutr Biochem, 2026, 150:110232. doi: 10.1016/j.jnutbio.2025.110232.
[28]	Ge Y, Huang S, Li Y, et al. Pregnancy thiamine and riboflavin intake and the risk of gestational diabetes mellitus: A prospective cohort study[J]. Am J Clin Nutr, 2023, 117(2):426-435. doi: 10.1016/j.ajcnut.2022.11.014.
[29]	Rad MG, Sharifi M, Meamar R, et al. Long term administration of thiamine disulfide improves FOXO1/PEPCK pathway in liver to reduce insulin resistance in type 1 diabetes rat model[J]. Biomed Pharmacother, 2024, 177:117053. doi: 10.1016/j.biopha.2024.117053.
[30]	Bakker SJ,ter Maaten JC,Gans RO. Thiamine supplementation to prevent induction of low birth weight by conventional therapy for gestational diabetes mellitus[J]. Med Hypotheses, 2000, 55(1):88-90. doi: 10.1054/mehy.1999.1037. pmid: 11021334
[31]	Aragão MÂ, Pires L, Santos-Buelga C, et al. Revitalising Riboflavin: Unveiling Its Timeless Significance in Human Physiology and Health[J]. Foods, 2024, 13(14):2255. doi: 10.3390/foods13142255.
[32]	Plows JF, Budin F, Andersson RA, et al. The Effects of Myo-Inositol and B and D Vitamin Supplementation in the db/+ Mouse Model of Gestational Diabetes Mellitus[J]. Nutrients, 2017, 9(2):141. doi: 10.3390/nu9020141.
[33]	Palawaththa S, Islam RM, Illic D, et al. Effect of maternal dietary niacin intake on congenital anomalies: a systematic review and meta-analysis[J]. Eur J Nutr, 2022, 61(3):1133-1142. doi: 10.1007/s00394-021-02731-9.
[34]	Tranidou A, Magriplis E, Apostolopoulou A, et al. Impact of Maternal Micronutrient Intake on Gestational Diabetes Risk: Results from Greece's BORN2020 Prospective Cohort Study[J]. Nutrients, 2024, 16(9):1375. doi: 10.3390/nu16091375.
[35]	Ma J, Li X, Li Q, et al. Niacin regulates glucose metabolism and osteogenic differentiation via the SIRT2-C/EBPβ-AREG signaling axis[J]. Biomed Pharmacother, 2024, 180:117447. doi: 10.1016/j.biopha.2024.117447.
[36]	Wei X, Tan Y, Huang J, et al. N1-methylnicotinamide impairs gestational glucose tolerance in mice[J]. J Mol Endocrinol, 2024, 72(2):e230126. doi: 10.1530/JME-23-0126.
[37]	Li M, Chen Y, Wang Y, et al. Maternal gestational diabetes in singleton pregnancies conceived by ART may be modified by periconceptional B vitamins[J]. Front Nutr, 2022, 9:1069911. doi: 10.3389/fnut.2022.1069911.
[38]	Lu Q, Li Y, Ye D, et al. Longitudinal metabolomics integrated with machine learning identifies novel biomarkers of gestational diabetes mellitus[J]. Free Radic Biol Med, 2023, 209(Pt 1):9-17. doi: 10.1016/j.freeradbiomed.2023.10.014.
[39]	Fields AM, Welle K, Ho ES, et al. Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice[J]. Commun Biol, 2021, 4(1):421. doi: 10.1038/s42003-021-01900-0. pmid: 33772108