Red blood cell (RBC) folate indicates long-term folate intake, and methylenetetrahydrofolate reductase (MTHFR) gene is the main gene affecting folate status. Increasing evidence suggests an association between gestational diabetes mellitus (GDM) and increased folate levels. Whether RBC folate concentrations in the first trimester of pregnancy or polymorphisms of MTHFR C677T (rs1801133) affect GDM risk in Chinese pregnant women remains unknown. Therefore, we analyzed the associations of RBC folate concentrations and rs1801133 polymorphisms with GDM risk among pregnant women in China. Methods: A total of 366 women with a singleton pregnancy were followed prospectively from their first prenatal visit to delivery. RBC folate concentrations and rs1801133 polymorphisms were assessed during the first trimester of pregnancy. Binary logistic regression analyses were performed to determine the odds ratios (ORs) of GDM and 95% confidence intervals (CIs) by using the RBC folate concentration quartiles and rs1801133 polymorphisms. Results: Participants with the TT genotype had the highest RBC folate concentrations. Those with heterozygous or homozygous variants did not have a significantly higher risk of GDM than did women with C alleles. After adjustments for covariates, women in the highest quartile for RBC folate concentration had a higher risk of GDM (adjusted OR = 2.473, 95% CI = 1.013-6.037, P = 0.047) than did those in the lowest quartile, but this association was nonsignificant after adjustment for rs1801133 polymorphisms. Conclusion: Higher RBC folate, partly caused by MTHFR 677C→T, may be associated with increased GDM risk, even in early pregnancy. Assessing RBC folate status and appropriately supplementing folate during early pregnancy, particularly for patients with MTHFR 677C→T, may prevent GDM. Further studies with larger populations are warranted.

Background/Aims: To investigate the potential of maternal first-trimester triglyceride (TG) to high-density lipoprotein cholesterol (TG/HDL-c) ratio, triglyceride glucose index (TyG) and total cholesterol (TC)/HDL-c to predict the risk of later gestational diabetes mellitus (GDM) and large for gestational age (LGA) newborn in Chinese women. Methods: We included 352 women with a singleton pregnancy, who were followed up prospectively from the first prenatal visit until delivery. Fasting glucose and plasma lipid profiles including TG, TC, HDL-c, and low-density lipoprotein cholesterol (LDL-c) were measured in the first trimester. A binary logistic regression analysis was performed to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and LGA according to tertiles of those indices, respectively. Receiver-operating characteristic curve (ROC) and areas under the curve (AUC) were employed to evaluate the ability of those indices to predict the risk of GDM and LGA infants, and differences in the AUC values between them were compared. Results: Women with the top tertile of TG/HDL-c or TyG other than TC/HDL-c had a significantly higher risk of GDM (OR TG/HDL-c =2.388, 95% CI 1.026-5.467; OR TyG =3.535, 95% CI 1.483-8.426, respectively) and LGA infant delivery (OR TG/HDL-c =3.742, 95% CI 1.114-12.569; OR TyG =3.011, 95% CI 1.012-8.962, respectively) than women with the lowest tertile of TG/HDL-c or TyG after adjusting for confounders. The AUC of TG/ HDL-c and TyG to detect GDM was 0.664 (95% CI 0.595-0.733) and 0.686 (95% CI 0.615-0.756), respectively, and that to detect LGA was 0.646 (95% CI 0.559-0.734) and 0.643 (95% CI 0.552-0.735), respectively (all P < 0.01). There were no statistical differences between TG/HDL-c and TyG in the ability of predicting the risk of GDM or LGA infants. Conclusion: Maternal first-trimester TG/HDL-c and TyG are both good indicators in predicting the risk of later GDM and LGA newborn, and it may be useful to evaluate them in early pregnancy.