A Longitudinal Study of Thyroid Markers Across Pregnancy and the Risk of Gestational Diabetes

Context: T3 is the biologically active thyroid hormone involved in glucose metabolism. The free T3 (fT3)/free T4 (fT4) ratio, a marker indicating conversion of fT4 to fT3, is also implicated in glucose homeostasis. Objective: To examine associations of fT3 and the fT3/fT4 ratio with gestational diabetes mellitus (GDM). Design: In a case-control study, thyroid markers (fT3, fT4, TSH) were measured and the fT3/fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10 to 14) and second (weeks 15 to 26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroidmarkers with subsequent GDM risk. Setting: Twelve US clinical centers. Participants: One hundred seven GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2802 women. Main Outcome Measures: GDM diagnosis ascertained from medical records. Results: Both fT3 and the fT3/fT4 ratio were positively associated with GDM: adjusted OR (95% CI) comparing the highest vs lowest fT3 quartile was 4.25 (1.67, 10.80) at the first trimester and 3.89 (1.50, 10.10) at the second trimester. Similarly, the corresponding risk estimates for the fT3/fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at the first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM. Conclusions: Higher fT3 levels, potentially resulting from de novo synthesis or increased fT4 to fT3 conversion, may be an indicator of GDM risk starting early in pregnancy.