Association of maternal triglyceride responses to thyroid function in early pregnancy with gestational diabetes mellitus

INTRODUCTION: The prevalence of Gestational Diabetes Mellitus (GDM) is increasing globally, and high levels of triglyceride (TG) and low levels of free thyroxine (FT4) in early pregnancy are associated with an increased risk of GDM; however, the interaction and mediation effects remain unknown. The aim of the present study is to examine the impact of FT4 and TG combined effects on the prevalence of GDM and the corresponding casual paths among women in early pregnancy. MATERIALS AND METHODS: This study comprised 40,156 pregnant women for whom early pregnancy thyroid hormones, fasting blood glucose as well as triglyceride were available. GDM was diagnosed using a 2-hour 75-g oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines, and the pregnant women were grouped and compared according to the results. RESULTS: An L-shaped association between FT4 and GDM was observed. The prevalence of GDM increased with increasing TG levels. After accounting for multiple covariables, the highest risk for GDM was found among pregnant women of lower FT4 with the highest TG concentrations (odds ratio, 2.44, 95% CI, 2.14 to 2.80; P<0.001) compared with mothers of higher FT4 with the TG levels in the lowest quartile (Q1). There was a significant interaction effect of maternal FT4 and TG levels on the risk for GDM (P for interaction = 0.036). The estimated proportion of the mediating effect of maternal TG levels was 21.3% (95% CI, 15.6% to 36.0%; P < 0.001). In the sensitivity analysis, the mediating effect of TG levels was stable across subgroups. CONCLUSION: This study demonstrated an L-shaped association between maternal FT4 levels and GDM and the benefit of low TG levels, in which maternal TG levels act as an important mediator in this association. Our findings suggested that pregnant women who treat hypothyroidism should also reduce triglycerides levels in early pregnancy to prevent GDM development.