Immunometabolic activation of neutrophils is associated with tissue factor-positive microparticles in gestational diabetes mellitus

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with chronic low-grade inflammation and an increased risk of thromboembolic complications. Tissue factor-positive microparticles (TF⁺MPs) link inflammatory and coagulation pathways, but their cellular origin and immunometabolic determinants in GDM remain unclear. OBJECTIVES: To characterize neutrophil-, monocyte-, and endothelial-derived TF⁺MPs in GDM and to assess their relationships with metabolic and inflammatory markers. PATIENTS AND METHODS: We studied 70 women with GDM and 55 healthy pregnant controls at 28-33 weeks' gestation. Neutrophil-derived (TF⁺CD66b⁺), monocyte-derived (TF⁺CD14⁺), and endothelial-derived (TF⁺CD144⁺) MPs were quantified by flow cytometry. Glycated hemoglobin (HbA1c) and interleukin-18 (IL-18) were measured as markers of recent glycemic exposure and inflammatory response, respectively. Statistical analyses included the Mann-Whitney U test, Cliff's delta, correlation analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: Women with GDM exhibited significantly higher counts of TF⁺CD66b⁺ MPs compared with controls (P <0.001; δ = 0.71). The percentage of TF⁺CD66b⁺ MPs relative to total TF⁺MPs showed marked separation between groups (AUC = 0.905). TF⁺CD14⁺ MPs were increased (P = 0.001; δ = 0.34), whereas TF⁺CD144⁺ MPs did not differ significantly (P = 0.29; δ = 0.11). TF⁺CD66b⁺ MPs correlated positively with HbA1c (R = 0.56, P <0.001) and IL-18 (R = 0.34, P = 0.004), with no associations observed for maternal BMI, fasting glucose, or glucose-lowering therapy. CONCLUSIONS: GDM is associated with marked enrichment of TF⁺CD66b⁺ MPs, reflecting immunometabolic neutrophil activation rather than obesity-related effects. These findings identify TF⁺CD66b⁺ MPs as a downstream marker linking metabolic and inflammatory pathways in GDM.