Free triiodothyronine and risk of gestational diabetes mellitus: an observational study and Mendelian randomization analysis.

IF 3.9 2区医学 Q2 NUTRITION & DIETETICS

Nutrition & Metabolism Pub Date : 2025-02-26 DOI:10.1186/s12986-025-00905-4

Yanan Li, Shuai Yang, Zixuan Huang, Yong Zhang, Haixia Guan, Jianxia Fan

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引用次数: 0

Abstract

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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游离三碘甲状腺原氨酸与妊娠期糖尿病的风险：一项观察性研究和孟德尔随机分析。

背景：游离三碘甲状腺原氨酸（FT3）对葡萄糖代谢有显著影响。妊娠期糖尿病（GDM）与FT3之间的关系复杂且报道不一致。我们的研究旨在探讨妊娠期FT3与GDM之间的双向关联，并评估这种关联是否存在因果关系。方法：观察性分析包括两项临床研究。研究1纳入6221名孕妇，应用多因素logistic回归分析，探讨妊娠早期FT3与GDM后续风险的关系。研究2纳入387例孕妇，采用线性回归分析GDM对妊娠后期FT3的影响。此外，利用FT3和GDM的全基因组关联研究（GWAS）汇总统计数据进行双向双样本孟德尔随机化（MR）分析，以检验因果关系。结果：在研究1中，在调整了潜在的混杂因素后，妊娠早期FT3水平升高与随后发生GDM的风险相关[比值比（OR） 1.122；95%置信区间（CI） 1.004, 1.255；P = 0.043]，限制三次样条分析显示线性相关（非线性P = 0.72）。在研究2中，我们没有发现妊娠后期GDM和FT3水平之间的关联。MR分析发现基因预测的FT3与GDM风险呈正相关(OR 1.26；95% ci 1.01, 1.57；P = 0.041)，而在反向MR中，GDM与FT3无显著关系。此外，敏感性分析说明了我们的MR结果的稳健性。结论：妊娠早期FT3水平与GDM风险呈正相关，MR分析提供了支持因果关系的证据。然而，未来的研究需要通过在不同种族人群中进行更大规模的GWAS来进一步调查这种关联，并探索潜在的生物学机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nutrition & Metabolism 医学-营养学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects. The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases. Key areas we wish to encourage submissions from include: -how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes; -the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components; -how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved; -how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.