Effects of Methionine Cycle Metabolites in Early Pregnancy on Gestational Diabetes Mellitus and Blood Glucose Levels: A Nested Case-Control Study

Objectives This study aimed to explore the impact of serum methionine cycle metabolite levels in the first trimester of pregnancy on the risk of GDM and blood glucose levels, providing new evidence for the prevention and control of GDM.Methods A nested case - control study design was adopted, and the research was carried out based on the prospective cohort project jointly established by the Institute of Reproductive and Child Health of Peking University and Haidian Maternal and Child Health Hospital. The original cohort collected information on the general demographic characteristics of pregnant women through questionnaires, and collected prenatal examination information (including blood glucose levels and GDM diagnosis) through the hospital information system. Residual blood from prenatal examinations was also collected for subsequent research. A total of 172 pregnant women diagnosed with GDM were selected from the original cohort as the case group, and healthy pregnant women were matched 1:1 as the control group according to certain conditions. High - performance liquid chromatography - tandem mass spectrometry (HPLC - MS/MS) was used to measure the concentrations of serum SAM, SAH, and Hcy in the first trimester of pregnancy. Conditional logistic regression was used to analyze the effects of SAM, SAH, Hcy levels, and the SAM/SAH ratio on GDM. Multiple linear regression was used to analyze the effects of the above - mentioned metabolite indicators on fasting blood glucose levels, 1 - hour and 2 - hour post - glucose - loading blood glucose levels in the second trimester of pregnancy.Results The median levels of serum SAM, SAH, and Hcy in the first trimester of pregnancy were 54.45 (38.18, 77.67) nmol/L, 47.74 (41.10, 55.47) nmol/L, and 4.38 (3.55, 5.22) μmol/L, respectively, and the SAM/SAH ratio was 1133.73 (756.48, 1726.26). There were no statistically significant differences between the case and control groups. Multivariate analysis showed that a higher SAH level increased the risk of GDM (Adjusted OR = 1.38, 95%CI: 1.04 ~ 1.83). There was no significant association between SAM, SAM/SAH, Hcy and GDM (p > 0.05). There was also no significant association between SAM, SAH, SAM/SAH, Hcy and blood glucose levels at each time point (p > 0.05).Conclusion High serum SAH levels in the first trimester of pregnancy are associated with a higher risk of GDM, suggesting the potential role of SAH in the early identification and screening of GDM. It also provides new clues for a better understanding of the pathogenesis of GDM.