Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 511436, China.
J Clin Endocrinol Metab. 2022 Jan 18;107(2):e804-e814. doi: 10.1210/clinem/dgab637.
While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear.
We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species.
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.
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, Ptrend = .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, Ptrend = .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.
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.
尽管甲状腺标志物与妊娠糖尿病（GDM）之间的关联已得到广泛研究，但结果尚无定论，其机制仍不清楚。
本研究旨在探讨早孕期甲状腺标志物与 GDM 风险的前瞻性关联，并通过脂质种类来检验其介导作用。
本研究纳入了来自同济-双流出生队列的 6068 名孕妇。在妊娠 15 周之前，检测了孕妇的血清甲状腺标志物（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）。通过 fT3/fT4 比值评估脱碘酶活性。在 883 名参与者的亚组中定量了血浆脂质组。
参与者的平均年龄为 26.6 ± 3.7 岁，平均妊娠周数为 10.3 ± 2.0 周。较高的 fT4 水平与 GDM 风险降低相关（极端四分位距比较的 OR = 0.73；95%CI 0.54，0.98；Ptrend =.043），而较高的 fT3/fT4 比值与 GDM 风险增加相关（极端四分位距比较的 OR = 1.43；95%CI 1.06，1.93；Ptrend =.010），调整了潜在混杂因素后结果仍然如此。多元线性回归提示 fT3/fT4 比值与烷基磷酸胆碱 36:1、磷脂酰乙醇胺质体 38:6、二酰甘油 18:0/18:1、神经鞘磷脂 34:1 和磷脂酰胆碱 40:7 呈正相关（错误发现率[FDR]校正 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综合效应介导的。
早孕期血清 fT4 浓度较低或 fT3/fT4 比值较高与 GDM 风险增加相关。fT3/fT4 比值与 GDM 的关联主要通过特定的脂质种类介导。
