Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes

by James E. Haddow, Wendy Y. Craig, Louis M. Neveux, Glenn E. Palomaki, Geralyn Lambert-Messerlian, Fergal D. Malone, Mary E. D'Alton, First and Second Trimester Risk of Aneuploidy (FaSTER) Research Consortium

Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11–14 weeks' gestation (first trimester) and 15–18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI 1.37–3.09] (unadjusted); and 1.89 [95% CI 1.26–2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97–2.16] (unadjusted) and 1.11 [95% CI 0.74–1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related low fT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.

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