Immunometabolic profiling related with gestational diabetes mellitus: a nested case-control study of CD4+ T cell phenotypes and glycemic traits.

Aims: To investigate immunometabolic associations of CD4⁺ T cell phenotypes with gestational diabetes mellitus (GDM).

Methods: 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.

Results: 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.

Conclusions: Treg cells and Foxp3 expressions were inversely associated with GDM risk, with potential metabolic mechanisms involving metabolites such as pyruvaldehyde and SAH.