Maternal insulin therapy during GDM may activate regulatory immune mechanisms in utero. The ISPAD 2025 Conference presented findings from an analysis of cord blood immune profiles in infants born to mothers with and without GDM.

The study evaluated 110 infants of mothers with GDM and 110 infants of non-GDM mothers. Cord blood mononuclear cells were analyzed using flow cytometry to quantify CD4+CD25+FOXP3+ regulatory T cells (Tregs). RT-PCR measured expression of FOXP3, NFATc2, STIM1, IL-10, IFN-γ, TNF-α, and TGF-β. Additional assays assessed Treg activity, cytokine secretion, autoantibodies, and responses to Toll-like receptor stimuli, including lipid A and peptidoglycans.

Infants of mothers with GDM showed a higher proportion of FOXP3+ cells within CD4+CD25(high) T cells. Insulin stimulation increased FOXP3+ frequencies and upregulated FOXP3, NFATc2, STIM1, IL-10, and TGF-β only in cells from these infants. Reduced NFATc2 and STIM1 responses occurred in cells carrying the PTPN22 allele associated with GDM. Elevated TNF-α, IL-10, and CD4+CD25+ T cells correlated with anti-GAD65 autoantibody levels. Maternal allergic history increased neonatal allergy risk. Lower Treg activity, reduced IL-10, and decreased FOXP3 expression independently predicted early-childhood allergy.

These findings indicate that maternal insulin therapy enhances fetal regulatory immune activity, while maternal allergies weaken this regulatory capacity.