目的:本研究旨在评估妊娠期糖尿病(GDM)与循环叶酸代谢产物之间的关系,叶酸(FA)摄入量,以及亚甲基四氢叶酸还原酶(MTHFR)和甲硫氨酸合成酶还原酶(MTRR)基因型。
方法:在北京进行了前瞻性妊娠队列研究,中国,从2022年到2023年。循环叶酸代谢物,包括红细胞(RBC)5-甲基四氢叶酸(5-MTHF),5,10-亚甲基-四氢叶酸(5,10-CH2-THF),5-甲酰基四氢叶酸(5-CHO-THF),和未代谢叶酸(UMFA),和血浆同型半胱氨酸(HCY),5-MTHF,和甲基丙二酸(MMA),在妊娠6-17周和20-26周确定。还检查了FA摄入量以及MTHFR和MTRR基因型。通过75g口服葡萄糖耐量试验(OGTT)在妊娠24至28周之间诊断为GDM。使用多变量广义线性模型确定叶酸状态与GDM之间的关联,逻辑回归模型,和限制三次样条回归,调整潜在的混杂因素。
结果:该研究包括2032名孕妇,其中392人(19.29%)患有GDM。高于第75百分位数的UMFA(≥P75)[调整后的OR(aOR)(95%置信区间[CI])=1.36(1.01-1.84)],UMFA≥P90[aOR(95%CI)=1.82(1.23-2.69)],妊娠早期HCY≥P75[aOR(95%CI)=1.40(1.04-1.88)],和RBC5-MTHF[aOR(95%CI)=1.48(1.10-2.00)],RBC5,10-CH2-THF[aOR(95%CI)=1.55(1.15-2.10)],妊娠中期血浆5-MTHF[aOR(95%CI)=1.36(1.00-1.86)]≥P75与GDM相关。妊娠早期较高的UMFA水平与OGTT期间的1小时和2小时葡萄糖水平呈正相关,和较高的HCY水平与OGTT期间空腹血糖水平升高有关。相比之下,RBC5-MTHF和5,10-CH2-THF,妊娠中期血浆5-MTHF与1小时血糖水平呈正相关(p<0.05)。MTHFR和MTRR基因型和FA摄入与GDM无关。
结论:妊娠早期UMFA和HCY水平升高,随着RBC5-MTHF和5,10-CH2-THF和血浆5-MTHF在怀孕中期升高,与GDM相关。这些发现表明不同叶酸代谢物与GDM的发生之间存在明显的联系。
OBJECTIVE: This
study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype.
METHODS: A prospective pregnancy cohort
study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders.
RESULTS: The
study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM.
CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.