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

Triiodothyronine (T3) is the biologically-active thyroid hormone involved in glucose metabolism. fT3:fT4 ratio, a marker indicating conversion of free thyroxine (fT4) to free T3 (fT3), is also implicated in glucose homeostasis. To examine associations of fT3 and fT3:fT4 ratio with gestational diabetes (GDM). In a case-control study, thyroid markers (fT3, fT4, TSH) were measured and fT3:fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10-14) and second (weeks 15-26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroid markers with subsequent GDM risk. 12 U.S. clinical centers. 107 GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2,802 women. GDM diagnosis ascertained from medical records. Both fT3 and fT3:fT4 ratio were positively associated with GDM; aOR (95% CI) comparing the highest vs. lowest fT3 quartile was 4.25 (1.67,10.80) at first and 3.89 (1.50, 10.10) at second trimester. Similarly, the corresponding risk estimates for fT3:fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM. Isolated hypothyroxinemia in the second, but not first trimester, was significantly related to increased GDM risk; aOR (95% CI) comparing hypothyroxinemic women to euthyroid was 2.97 (1.07,8.24). 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.

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