Associations between Human Chorionic Gonadotropin, Maternal Free Thyroxine, and Gestational Diabetes Mellitus

Abstract

Background: Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM and whether it is mediated through maternal thyroid hormones. Methods: This study included 18,683 pregnant women presenting at a tertiary hospital in Shanghai, China, between January 2015 and December 2016. GDM was diagnosed using a 2-hour, 75-g, oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines. Multivariable logistic or linear regression models were used to identify associations, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroperoxidase antibody (TPOAb) status, and prepregnancy body-mass index. Results: Higher hCG concentrations were associated with a lower plasma glucose level during the OGTT, but not with fasting plasma glucose or hemoglobin A1c concentrations tested during early pregnancy. hCG in early pregnancy was negatively associated with GDM risk ( p = 0.027). Mediation analysis identified that an estimated 21.4% of the association of hCG-associated GDM risk was mediated through changes in free thyroxine (fT4) concentrations ( p < 0.05). In the sensitivity analysis restricted to TPOAb-positive women, hCG was not associated with GDM ( p = 0.452). Conclusions: Higher hCG levels in early pregnancy are associated with a lower risk of GDM. Maternal fT4 may act as an important mediator in this association.

Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex

“…Despite some controversy, perhaps due to different composition of patient cohorts and/or heterogeneous diagnostic criteria for GDM, an increasing body of evidence suggests a link of maternal serum hCG and maternal glucose metabolism. Accordingly, hCG and free β-hCG in early pregnancy is negatively associated with GDM risk [ 47 , 48 , 49 , 50 ]. This association has been confirmed in GDM-derived primary trophoblasts, which showed significantly decreased expression of genes associated with differentiation, including impaired synthesis of the hCG-beta subunit [ 51 ].…”

“…However, physiological concentrations of insulin inhibit hCG secretion in first trimester placenta explants [ 54 ] and the release of β-hCG from trophoblast cell line JAR, when cultured in absence of fetal calf serum [ 55 ]. Another recently suggested signaling route through which hCG may be associated with GDM is the thyrotropin (TSH) receptor axis [ 47 ]. By its weak affinity for the TSH receptor, hCG has been suggested to stimulate the thyroid gland and increase serum free thyroxine, which promotes insulin secretion and maintains glucose homeostasis.…”

Increased Central and Peripheral Thyroid Resistance Indices During the First Half of Gestation Were Associated With Lowered Risk of Gestational Diabetes—Analyses Based on Huizhou Birth Cohort in South China

“…Thyroid gland enlarges nearly by 40%, and its hormone production increases by 50% during gestation ( 1 ). In early pregnancy, increased placental human chorionic gonadotropin (HCG) stimulates thyroid hormones [THs, including thyroxine (T4) and triiodothyronine (T3)] secretion and causes a reduction in thyroid-stimulating hormone (TSH) ( 2 , 3 ). Thyroid diseases are the second most common endocrine disorders affecting women of reproductive age ( 4 ).…”

Non-Assisted Hatching Trophectoderm Biopsy Does Not Increase The Risks of Most Adverse Maternal and Neonatal Outcome and May Be More Practical for Busy Clinics: Evidence From China

“…hCG can lead to thyroid-stimulating hormone (TSH) activity and induce free thyroxine (FT4) surge (34,35), facilitate early placentation to indirectly affect insulin resistance (IR) derived by placental endocrine (36), and play as an immune modulator to alleviate pancreatic autoimmunity (37). Liu et al (38) demonstrated that higher hCG levels in early pregnancy were associated with a lower risk of GDM and maternal FT4 which may act as an important mediator (24%) in this association. While some scholars (39,40) claim that TE biopsy might reduce the level of serum beta-hCG in early pregnancies, this is still controversial (41).…”