A Prospective Study of Early-pregnancy Thyroid Markers, Lipid Species, and Risk of Gestational Diabetes Mellitus

Context: While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear. Objective: We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species. Methods: This study included 6068 pregnant women from the Tongji-Shuangliu Birth Cohort. Maternal serum thyroid markers (free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody) were measured before 15 weeks. Deiodinase activity was assessed by fT3/fT4 ratio. Plasma lipidome were quantified in a subset of 883 participants. Results: Mean age of the participants was 26.6 +/- 3.7 years, and mean gestational age was 10.3 +/- 2.0 weeks. Higher levels of fT4 were associated with a decreased risk of GDM (OR = 0.73 comparing the extreme quartiles; 95% CI 0.54, 0.98, P-trend = .043), while higher fT3/fT4 ratio was associated with an increased risk of GDM (OR = 1.43 comparing the extreme quartiles; 95% CI 1.06, 1.93, P-trend = .010) after adjusting for potential confounders. Multiple linear regression suggested that fT3/fT4 ratio was positively associated with alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, sphingomyelin 34:1, and phosphatidylcholine 40:7 (false discovery rate [FDR] adjusted P < .05). Mediation analysis indicated 67.9% of the association between fT3/fT4 ratio and GDM might be mediated through the composite effect of these lipids. Conclusion: Lower concentration of serum fT4 or higher fT3/fT4 ratio in early pregnancy was associated with an increased risk of GDM.The association of fT3/fT4 ratio with GDM was largely mediated by specific lipid species.