Free-Triiodothyronine to Free-Thyroxine Ratio Mediated the Effect of Prepregnancy Body Mass Index or Maternal Weight Gain During Early Pregnancy on Gestational Diabetes Mellitus

Maternal overweight or obesity during early pregnancy can increase the subsequent risk of gestational diabetes mellitus (GDM). However, whether these associations are mediated by thyroid hormones and their effect sizes is still unknown. This study aimed to identify the mediating effects of thyroid parameters between prepregnancy body mass index (BMI) or maternal weight gain during early pregnancy on the subsequent risk of GDM.This prospective mother-infant cohort study was conducted from 2018 to 2019. A total of 2772 singleton pregnant women were included in the analysis. A questionnaire survey, anthropometric measures, and thyroid function testing were conducted during early pregnancy. Deiodinase activity was evaluated using the free-triiodothyronine-to-free-thyroxine ratio (FT3:FT4). The standard 75-g oral glucose tolerance test was performed during 24 to 28 weeks of gestation to diagnose GDM. A mediation analysis was performed using PROCESS 3.5 to examine the mediating effects of thyroid parameters between prepregnancy BMI or maternal weight gain during early pregnancy on the subsequent risk of GDM.The FT3:FT4 ratio was a significant mediator between prepregnancy BMI or maternal weight gain and GDM, accounting for 16.5% and 18.6% of total effects, respectively. FT3 also mediated the association of prepregnancy BMI with GDM, accounting for 3.3% of the total effects. Thyroid-stimulating hormone suppressed the effects of prepregnancy BMI and maternal weight gain on GDM risk, and the proportion of their total effects was 2.4% and 6.4%, respectively.Deiodinase activity, as indicated by the FT3:FT4 ratio, was the strongest mediator among thyroid parameters between prepregnancy BMI or maternal early weight gain and GDM.