Abstract

ObjectivesThe study aimed to explore the relationship of thyroid function and resistance indices with subsequent risk of gestational diabetes (GDM).DesignThis was a longitudinal study embedded in the Huizhou Birth Cohort.MethodsA total of 2,927 women of singleton pregnancy were recruited from January to October of 2019. Thyroid central resistance indices were evaluated by Thyroid Feedback Quartile-Based index (TFQI), Thyrotrophy T4 Resistance Index (TT4RI), and TSH Index (TSHI) based on plasma-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels during the first half of pregnancy. Thyroid peripheral sensitivity was assessed by free triiodothyronine (FT3) to FT4 ratio (FT3/FT4), a proxy of deiodinase activity. GDM was diagnosed between 24 and 28 weeks of gestation by a standardized 75 g oral glucose tolerance test. Multivariable linear and logistic regression was applied to examine the associations of thyroid markers with GDM risk.ResultsFT3 and FT3/FT4 were positively associated with both fasting and post-load glucose levels, while TSH, TSHI, TT4RI, and TFQI were negatively associated with 1 and 2 h post-load glucose levels. Compared with the lowest quartile, GDM risk in the highest quartile increased by 44% [odds ratio (OR) = 1.44; 95%CI, 1.08–1.92; ptrend = 0.027] for FT3 and 81% (OR = 1.81; 95%CI, 1.33–2.46; ptrend < 0.001) for FT3/FT4, while it lowered by 37% (OR = 0.63; 95%CI, 0.47–0.86; ptrend = 0.002] for TSHI, 28% for TT4RI (OR = 0.72; 95%CI, 0.54–0.97; ptrend = 0.06), and 37% for TFQI (OR = 0.63; 95%CI, 0.46–0.85; ptrend < 0.001).ConclusionsThis longitudinal study indicated that higher FT3 and FT3/FT4 and lower central thyroid resistance indices were associated with increased risk of GDM.

Highlights

  • Pregnancy has a considerable impact on thyroid function

  • Multivariable linear regression was applied with adjustment being made for maternal age, education, smoking and alcohol drinking during early pregnancy, body mass index (BMI) of pre-pregnancy, multi-parity, and family history of diabetes. b, standardized coefficients; FT3, free triiodothyronine; FT4, free thyroxine; thyroid-stimulating hormone (TSH), thyroidstimulating hormone; TSHI, TSH Index; TT4RI, Thyrotroph T4 Resistance Index

  • TFQI indicated the difference between FT4 quantile and the reversed TSH quantile; Cdf denoted cumulative distribution function

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Summary

Introduction

Pregnancy has a considerable impact on thyroid function. 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]. About 10%–15% of pregnant women suffer from thyroid disorders during pregnancy including overt and subclinical hyper- or hypothyroidism [2, 5]. Maternal thyroid disorders have been often associated with adverse obstetric complications and outcomes [2, 6]. The utility of thyroid function screening during early pregnancy is still controversial, and its implementation varied from country to country [2]

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