A Prospective Study of Early-pregnancy Thyroid Markers, Lipid Species, and Risk of Gestational Diabetes Mellitus
A Prospective Study of Early-pregnancy Thyroid Markers, Lipid Species, and Risk of Gestational Diabetes Mellitus
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一项关于早孕甲状腺标志物、脂质种类和妊娠糖尿病风险的前瞻性研究。
DOI：
10.1210/clinem/dgab637
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发表时间：
2022-02-01
影响因子：
5.8
通讯作者：
Pan, An
中科院分区：
文献类型：
--
作者：
Wang, Yi;Sun, Fengjiang;Pan, An
背景：虽然甲状腺标志物与妊娠期糖尿病（GDM）之间的关联已被广泛研究，但结果尚无定论，其机制仍不清楚。目的：我们旨在探讨妊娠早期甲状腺标志物与 GDM 风险的前瞻性关联，并通过脂质种类检验其中介作用。方法：本研究纳入了来自同济-双流出生队列的 6068 名孕妇。 15周前测量母体血清甲状腺标志物（游离三碘甲状腺原氨酸（fT3）、游离甲状腺素（fT4）、促甲状腺激素、甲状腺过氧化物酶抗体和甲状腺球蛋白抗体）。脱碘酶活性通过fT3/fT4比率来评估。对 883 名参与者的子集进行血浆脂质组定量。结果：参与者的平均年龄为 26.6 +/- 3.7 岁，平均孕龄为 10.3 +/- 2.0 周。较高水平的 fT4 与 GDM 风险降低相关（比较极端四分位数 OR = 0.73；95% CI 0.54, 0.98，P-趋势 = .043），而较高的 fT3/fT4 比率与 GDM 风险增加相关（比较极端四分位数 OR = 1.43；95% CI 1.06, 1.93，P-趋势 = .010）在调整潜在的混杂因素后。多元线性回归表明，fT3/fT4 比率与烷基磷脂酰胆碱 36:1、磷脂酰乙醇胺缩醛磷脂 38:6、二酰甘油 18:0/18:1、鞘磷脂 34:1 和磷脂酰胆碱 40:7 呈正相关（错误发现率 [FDR] 调整后 P < .05）。中介分析表明，fT3/fT4 比值与 GDM 之间的关联有 67.9% 可能是通过这些脂质的复合效应介导的。结论：妊娠早期血清 fT4 浓度较低或较高的 fT3/fT4 比值与 GDM 风险增加相关。fT3/fT4 比值与 GDM 的关联很大程度上是由特定脂质种类介导的。
Context: While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear.Objective: We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species.Methods: This study included 6068 pregnant women from the Tongji-Shuangliu Birth Cohort. Maternal serum thyroid markers (free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody) were measured before 15 weeks. Deiodinase activity was assessed by fT3/fT4 ratio. Plasma lipidome were quantified in a subset of 883 participants.Results: Mean age of the participants was 26.6 +/- 3.7 years, and mean gestational age was 10.3 +/- 2.0 weeks. Higher levels of fT4 were associated with a decreased risk of GDM (OR = 0.73 comparing the extreme quartiles; 95% CI 0.54, 0.98, P-trend = .043), while higher fT3/fT4 ratio was associated with an increased risk of GDM (OR = 1.43 comparing the extreme quartiles; 95% CI 1.06, 1.93, P-trend = .010) after adjusting for potential confounders. Multiple linear regression suggested that fT3/fT4 ratio was positively associated with alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, sphingomyelin 34:1, and phosphatidylcholine 40:7 (false discovery rate [FDR] adjusted P < .05). Mediation analysis indicated 67.9% of the association between fT3/fT4 ratio and GDM might be mediated through the composite effect of these lipids.Conclusion: Lower concentration of serum fT4 or higher fT3/fT4 ratio in early pregnancy was associated with an increased risk of GDM.The association of fT3/fT4 ratio with GDM was largely mediated by specific lipid species.