Immunometabolic activation of neutrophils is associated with circulating tissue factor-positive microparticle profile in gestational diabetes mellitus.

Abstract

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 endothelium‑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 endothelium‑derived (TF⁺CD144⁺)  MPs were quantified by flow cytometry. Levels of glycated hemoglobin (HbA_1c) and interleukin‑18 (IL‑18) were measured as markers of glycemic exposure and inflammatory response, respectively. Statistical analyses included the Mann-Whitney test, Cliff delta (δ), correlation analysis, and receiver operating characteristic curve analysis.

Results: The women with GDM exhibited significantly higher counts of TF⁺CD66b⁺ MPs than the controls (δ = 0.71; P <0.001). The percentage of TF⁺CD66b⁺ MPs relative to the total TF⁺MP count showed marked separation between the groups (area under the curve, 0.905). The TF⁺CD14⁺ MP count was increased in GDM (δ = 0.34; P = 0.001), whereas the TF⁺CD144⁺ MP count did not differ between the groups (δ = 0.11; P = 0.29). The TF⁺CD66b⁺ MP count correlated positively with HbA_1c (R = 0.56; P <0.001) and IL‑18 (R = 0.34; P = 0.004) levels, with no significant associations observed for maternal body mass index, fasting glucose level, or glucose‑lowering therapy.

Conclusions: GDM was 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.