Wei Xiaohui, Sun Zhuo, Wang Na, Deng Zequn, Li Wenyun, Ying Tao, Wu Min, Liu Yuwei, He Gengsheng
School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, No.130, Dong'an Road, Xuhui District, Shanghai, 200032, China.
Nursing Department, Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, 200011, China.
Acta Diabetol. 2025 Jan;62(1):77-85. doi: 10.1007/s00592-024-02338-6. Epub 2024 Aug 15.
To investigate immunometabolic associations of CD4 T cell phenotypes with gestational diabetes mellitus (GDM).
A nested case-control study was conducted comprising 53 pairs of GDM patients and matched controls within a prospective cohort. Metabolomic signatures related to both CD4 T cell phenotypes and glycemic traits among pregnant women were investigated by weighted gene co-expression network analysis (WGCNA). Multivariable-adjusted generalized linear models were used to explore the associations of CD4 T cell phenotypes and selected metabolites with GDM. Mediation analysis was conducted to evaluate the mediating effect of selected metabolites on the relationship between CD4 T cell phenotypes and glycemic traits.
Higher levels of Treg cells (OR per SD increment (95%CI): 0.57 (0.34, 0.95), p = 0.031) and increased expression of Foxp3 (OR per SD increment (95%CI): 0.59 (0.35, 0.97), p = 0.039) and GATA3 (OR per SD increment (95%CI): 0.42 (0.25, 0.72), p = 0.002) were correlated with a decreased risk of GDM. Plasma pyruvaldehyde, S-adenosylhomocysteine (SAH), bergapten, and 9-fluorenone mediated the association between Tregs and fasting plasma glucose (FPG), with mediation proportions of 46.9%, 39.6%, 52.4%, and 56.9%, respectively.
Treg cells and Foxp3 expressions were inversely associated with GDM risk, with potential metabolic mechanisms involving metabolites such as pyruvaldehyde and SAH.
研究CD4 T细胞表型与妊娠期糖尿病（GDM）之间的免疫代谢关联。
在一项前瞻性队列研究中进行了一项巢式病例对照研究，包括53对GDM患者及其匹配的对照。通过加权基因共表达网络分析（WGCNA）研究孕妇中与CD4 T细胞表型和血糖特征相关的代谢组学特征。使用多变量调整的广义线性模型来探讨CD4 T细胞表型和选定代谢物与GDM的关联。进行中介分析以评估选定代谢物对CD4 T细胞表型与血糖特征之间关系的中介作用。
较高水平的调节性T细胞（Treg，每标准差增加的比值比（95%置信区间）：0.57（0.34，0.95），p = 0.031）以及叉头框蛋白3（Foxp3）（每标准差增加的比值比（95%置信区间）：0.59（0.35，0.97），p = 0.039）和GATA结合蛋白3（GATA3）（每标准差增加的比值比（95%置信区间）：0.42（0.25，0.72），p = 0.002）表达增加与GDM风险降低相关。血浆丙酮醛、S-腺苷同型半胱氨酸（SAH）、补骨脂素和芴酮介导了Treg与空腹血糖（FPG）之间的关联，中介比例分别为46.9%、39.6%、52.4%和56.9%。
Treg细胞和Foxp3表达与GDM风险呈负相关，潜在的代谢机制涉及丙酮醛和SAH等代谢物。
