Circulating neutrophil extracellular traps and deoxyribonuclease in gestational diabetes mellitus

Neutrophil extracellular traps (NETs) are networks of extracellular DNA, protein and enzymes formed by activated neutrophils and degraded by deoxyribonuclease (DNase). Maternal circulating NETs levels are altered in placental dysfunction-related pregnancy complications, including preeclampsia. Placental dysfunction is also a feature of gestational diabetes mellitus (GDM), but the role of NETs in GDM is understudied. We assessed maternal circulating NETs biomarkers in GDM women compared to controls, and explored associations with glycemic control, treatment modality and placental dysfunction. We analyzed third trimester serum and plasma from GDM women (n = 132) and euglycemic control pregnancies (n = 1126) for the NETs biomarkers myeloperoxidase (MPO)-DNA, citrullinated histone H3 (CitH3) and DNase, as well as markers of placental dysfunction (soluble fms-like tyrosine kinase-1 and placental growth factor) and glycemic control. Kruskal-Wallis H test and median regression analysis were employed, with significance set at p < 0.05. Median maternal circulating MPO-DNA levels were lower in GDM women compared to controls (p < 0.001), without significant differences in CitH3 and DNase levels. There were no differences in NETs biomarker levels between insulin and diet-controlled GDM women, nor associations between NETs and placental dysfunction markers or glucose parameters in multivariable analyses. GDM women had lower or similar circulating NETs biomarker levels compared to euglycemic controls. This suggests that dysregulated NETs are not a characteristic feature of GDM, at least not in a well-regulated population, or that NETs accumulate in other tissues like the placenta. In GDM, the processes determining circulating NETs levels and placental dysfunction appear unlinked.