School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Sep 25;14:1007192. doi: 10.3389/fendo.2023.1007192. eCollection 2023.
To explore the relationship between folic acid supplementation and the recovery rate of gestational diabetes mellitus (GDM) in women with methylenetetrahydrofolate () 677 TT genotypes in mid-late pregnancy.
9, 096 pregnant women were recruited with their gene genotyped. 5,111 women underwent a 75-g oral glucose tolerance test (OGTT) and 2,097 were confirmed with GDM. The association between genotypes and GDM risk was estimated using logistic and log-binomial regression, with age and parity set as the covariates to control their confounding effects. Further assessment of GDM risk on glucose levels was done using the ANCOVA model. As an open-label intervention study, 53 GDM patients with TT genotype were prescribed 800μg/day of folic acid as the high-dose group, while 201 GDM patients were given 400μg/day as the standard-dose group at their 24-28 weeks of pregnancy. A rate ratio (RR) of GDM recovery was estimated at each available time point for both groups. The time-to-GDM persistence events were analyzed with the Kaplan-Meier method and Cox-regression model. The trend of glucose levels over time was estimated using the linear model.
677 TT genotype has no significant association with the glucose levels and GDM risk, with an adjusted OR of 1.105 (95% CI 0.853, 1.431; p=0.452) and an adjusted PR of 1.050 (95% CI 0.906, 1.216; p=0.518) compared to the wildtype CC group. Patients in the high-dose group (n=38; 15 drop-outs; 40.69 days (95% CI 33.22, 48.15)) recovered from GDM approximately 27 days faster than those in the standard-dose group (n=133; 68 drop-outs; 68.09 days (95% CI 63.08, 73.11)). Concomitantly, the RR of GDM recovery rose and reached 1.247 (95% CI 1.026, 1.515) at 100 days of treatment with the standard-dose group as reference.
High-dose folic acid supplement intake in mid-late pregnancy is associated with faster GDM relief in patients with 677 TT genotype compared to the standard dose, which would be served as a novel and low-cost alternative therapy for the treatment of GDM.
探讨中晚期妊娠女性亚甲基四氢叶酸还原酶（）677 TT 基因型与叶酸补充剂对妊娠期糖尿病（GDM）恢复率的关系。
招募了 9096 名孕妇进行基因分型。5111 名孕妇进行了 75g 口服葡萄糖耐量试验（OGTT），2097 名孕妇确诊为 GDM。使用逻辑回归和对数二项式回归估计 基因型与 GDM 风险的关联，以年龄和产次为协变量，以控制其混杂效应。使用协方差分析模型进一步评估 GDM 对血糖水平的风险。作为一项开放性标签干预研究，将 53 名 TT 基因型的 GDM 患者随机分为高剂量组（每天 800μg 叶酸）和标准剂量组（每天 400μg 叶酸），在妊娠 24-28 周时进行治疗。估计两组在每个可获得的时间点 GDM 恢复的率比（RR）。使用 Kaplan-Meier 方法和 Cox 回归模型分析 GDM 持续时间的时间趋势。使用线性模型估计血糖水平随时间的变化趋势。
677 TT 基因型与血糖水平和 GDM 风险无显著关联，与野生型 CC 组相比，调整后的 OR 为 1.105（95%CI 0.853，1.431；p=0.452），调整后的 PR 为 1.050（95%CI 0.906，1.216；p=0.518）。与标准剂量组（n=133；68 例失访；68.09 天（95%CI 63.08，73.11））相比，高剂量组（n=38；15 例失访；40.69 天（95%CI 33.22，48.15））的 GDM 患者恢复时间平均快 27 天。同时，以标准剂量组为参照，治疗 100 天时，GDM 恢复的 RR 升高至 1.247（95%CI 1.026，1.515）。
与标准剂量相比，中晚期妊娠高剂量叶酸补充剂摄入与 677 TT 基因型患者的 GDM 缓解更快相关，这可能为 GDM 的治疗提供一种新的、低成本的替代治疗方法。
