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Published on: October 6, 2023
Free triiodothyronine and risk of gestational diabetes mellitus: an observational study and Mendelian randomization
Yanan Li1,2,3, Shuai Yang1,2,3, Zixuan Huang1,2,3
1Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Background:
Free triiodothyronine (FT3) exerts a significant influence on glucose metabolism. The relationship between gestational diabetes mellitus (GDM) and FT3 during pregnancy is complex and inconsistently reported. Our study aims to explore the bidirectional association between FT3 during pregnancy and GDM, and to assess whether this association is causal.
Methods:
The observational analysis included two clinical studies. Study 1 involved 6,221 pregnant women and applied multivariate logistic regression analysis to investigate the association between FT3 in early pregnancy and the subsequent risk of GDM. Study 2 comprised 387 pregnant women and employed linear regression analysis to examine the impact of GDM on FT3 in late pregnancy. Additionally, genome-wide association study (GWAS) summary statistics of FT3 and GDM were used to perform a bidirectional two-sample Mendelian randomization (MR) analysis to test for causal associations.
Results:
In Study 1, after adjusting for potential confounding factors, increased FT3 levels in early pregnancy were associated with the subsequent risk of GDM [odds ratio (OR) 1.122; 95% confidence interval (CI) 1.004, 1.255; P = 0.043], and the restricted cubic spline analysis indicated a linear association (P for nonlinearity = 0.72). In Study 2, we didn't find association between GDM and FT3 levels in late pregnancy. MR analysis found a positive causal relationship of genetically predicted FT3 on the risk of GDM (OR 1.26; 95% CI 1.01, 1.57; P = 0.041), while in the reverse MR, there was no significant relationship of GDM on FT3. In addition, the sensitivity analysis illustrated the robustness of our MR results.
Conclusions:
FT3 levels in early pregnancy were positively associated with the risk of GDM, and MR analysis provided evidence supporting a causal relationship. However, future studies are required to further investigate this association through larger-scale GWAS in diverse ethnic populations and to explore the underlying biological mechanisms.
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