Free T4 may mediate association between pregnancy hormone, gestational diabetes risk
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A high human chorionic gonadotropin level in early pregnancy is associated with lower risk for developing gestational diabetes, with maternal free thyroxine level acting as an important mediator, according to data published in Thyroid.
“Human chorionic gonadotropin (hCG) is a marker of placental function, and higher hCG is associated with a lower postprandial glucose and lower risk of gestational diabetes mellitus,” Tim Korevaar, MD, PhD, a translational epidemiologist at the Academic Center for Thyroid Diseases at Erasmus Medical Center in Rotterdam, the Netherlands, told Healio. “About one-fifth of the positive effects of hCG could be mediated via thyroid stimulation by hCG.”
Korevaar and colleagues analyzed data from 18,683 pregnant women presenting at a tertiary hospital in Shanghai from 2015 to 2016 (mean age, 29 years; mean gestational age, 12.1 weeks; 84.5% primiparous). Gestational diabetes was diagnosed using a 2-hour, 75 g oral glucose tolerance test, according to American Diabetes Association guidelines. Researchers used logistic or linear regression models to identify associations between hCG, free T4 and gestational diabetes risk, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroid peroxidase antibody (TPOAb) status and prepregnancy BMI.
Within the cohort, median thyroid-stimulating hormone was 1.15 mU/L, median free T4 was 15 pmol/L, and 1,833 women (9.8%) were TPOAb positive.
Researchers found that higher hCG concentrations were associated with a lower plasma glucose level during the OGTT, but not with fasting plasma glucose or HbA1c measurements during early pregnancy. Early pregnancy hCG was negatively associated with gestational diabetes risk (P = .027).
In mediation analysis, researchers found an estimated 21.4% of the association of hCG-associated gestational diabetes risk was mediated through changes in free T4 concentrations (P < .05). In sensitivity analyses restricted to TPOAb-positive women, hCG was not associated with gestational diabetes.
The researchers noted that the findings offer new insights into the potential mechanism involved in the development of glucose intolerance.
“These data provide new insights into how thyroid physiology could affect the risk for gestational diabetes, after replication of which, these data can be used to identify high-risk populations,” Korevaar said. “It will be relevant to study the mechanism via which hCG may have a beneficial effect on glucose homeostasis, and further studies on the relevance of adequate hCG stimulation of thyroid function during pregnancy are needed to improve the clinical risk assessment related to thyroid function test abnormalities in pregnancy.”
For more information:
Tim Korevaar, MD, PhD, can be reached at t.korevaar@erasmusmc.nl; Twitter: @TimKorevaar.
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