Maternal Plasma Betaine in Middle Pregnancy Was Associated with Decreased Risk of GDM in Twin Pregnancy: A Cohort Study

PURPOSE: Although previous studies have shown that choline-related metabolites in one carbon metabolism (OCM) were related to gestational diabetes mellitus (GDM) risk in singleton pregnancy, their role in twin gestations remains unclear. We aimed to investigate the associations between choline, betaine, methionine, dimethylglycine (DMG), trimethylamine N-oxide (TMAO) and GDM risk among women with twin gestations. PATIENTS AND METHODS: This hospital-based cohort study included 187 women with dichorionic twin gestations. Blood samples were collected during pregnancy at a median of 16.1 weeks of gestation (IQR: 13.9 −17.9). Concentrations of plasma metabolites were measured by HPLC-triple quadrupole MS. Log-binomial regression models were applied to estimate the associations between plasma metabolites and the risk of GDM. RESULTS: A total of 57 (30.5%) GDM cases were diagnosed over the study follow-up. Eighty-seven percent of women conceived through ART. Plasma betaine had an inverse association with GDM risk, and the adjusted RR of GDM comparing the highest tertile with the lowest tertile was 0.41 (95% CI: 0.19–0.86, P(trend)=0.015). Women with a high betaine/choline ratio or a low DMG/betaine ratio were at decreased GDM risk (P(trend)=0.031 or 0.001, respectively). Plasma choline, methionine, DMG and TMAO were not associated with GDM risk. CONCLUSION: Among women with dichorionic twin gestations, higher plasma level of betaine in the second trimester was associated with lower risk of GDM. This finding needs further confirmation.