Higher Thyroid fT3-to-fT4 Ratio Is Associated with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes

Abstract

Aim: To determine the association between thyroid function and the risk of developing gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. Methods: This case–control study was a sub-analysis of the BEDIP-N study, in which 199 GDM women were matched for age and body mass index with 398 controls. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and thyroid peroxidase (TPO) antibodies were measured at 6–14 weeks and 26–28 weeks during pregnancy. TSH and fT4 were also measured in early postpartum in GDM women. Results: The fT3-to-fT4 ratio at 26–28 weeks was positively associated with GDM risk with an adjusted odds ratio (aOR for smoking, education, parity, ethnicity, gestational weight gain, and (family) history of diabetes or GDM) of 2.12 (95% CI 1.07; 4.23), comparing the highest with the lowest tertile. Higher fT3 levels and a higher fT3-to-fT4 ratio were associated with a less favorable metabolic profile with higher BMI and more insulin resistance during pregnancy and postpartum. Women in the upper fT3 tertile and the upper fT3-to-fT4 ratio had a higher rate of preeclampsia [4.6% (10) vs. 1.0% (2), p = 0.040, and 4.4% (9) vs. 0.5% (1), p = 0.020], gestational hypertension [8.3% (18) vs. 3.1% (6), p = 0.034 and 8.9% (18) vs. 2.0% (4), p = 0.003], and caesarean sections [29.4% (63) vs. 16.1% (31), p = 0.002 and 32.2% (65) vs. 12.7% (25), p < 0.001]. Conclusion: A higher fT3-to-fT4 ratio late into pregnancy was associated with GDM, adverse pregnancy outcomes, and an adverse metabolic profile in early postpartum.

Free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio identified as a risk factor for gestational diabetes in euthyroid pregnant women: insights from a Chinese population cohort study

“…It is theorized that the increased deiodinase activity triggered by BMI may elevate the risk of GDM by amplifying the effects of T3 (11). A recent study has reported similar findings, indicating that a higher FT3-to-FT4 ratio during the later stages of pregnancy was linked to an increased risk of GDM, adverse pregnancy outcomes, and an adverse metabolic profile in the early postpartum period (12). Nonetheless, it is worth noting that the study had a relatively small sample size, and it was unable to demonstrate the predictive value of FT3/FT4 for the occurrence of GDM.…”

Assessment of the association between genetic factors regulating thyroid function and microvascular complications in diabetes: A two-sample Mendelian randomization study in the European population

“…Another MR study showed that genetically based high FT3/FT4 was associated with an increased risk of atrial fibrillation (12). In addition, a Belgian report showed that FT3:FT4 in late pregnancy was positively associated with gestational diabetes, adverse pregnancy outcomes and poor metabolic profile in the early postpartum period (7).…”

“…Thyroid-related diseases and diabetes mellitus are two of the most significant metabolic disorders that have a well-documented association (7)(8)(9). The presence of thyroid hormone receptors in the vascular endothelial tissue means that alterations in circulating thyroid hormone levels can contribute to the development and progression of vascular disease (10).…”