CONICET | Buscador de Institutos y Recursos Humanos

Introduction and ObjectiveDiabetes is characterized by chronic inflammation, endothelial dysfunction, increased riskof infections and early cardiovascular disease. By releasing neutrophil extracellular traps(NETs), neutrophils kill bacteria and exert pro-inflammatory and pro-thrombotic activities.Increased NETosis has been found in cross-sectional studies including treated type 2 diabetesmellitus (T2DM) patients. In this study, we determined whether the ability of neutrophilsto form NETs differs in diabetic patients pre- and post-hyperglycemic control versus healthydonors (HD), and the relationship between NETosis with pro-thrombotic, pro-inflammatorybiomarkers and thrombotic clinical events.MethodsDiabetic patients recently diagnosed and after 6 and 12 months of treatment (N = 25) andHD (N = 25) were included. NET formation was studied by microscopy and fluorometry.Nucleosomes, HNE-DNA complexes, von Willebrand factor (vWF), IL6 and TNFα plasmalevels were measured by ELISA and P-selectin on the platelet surface was assessed bycytometry.ResultsBasal levels of NETs in recently diagnosed T2DM patients were higher compared to HD.While TNFα stimulation of control neutrophils resulted in DNA release, patient neutrophilswere not responsive. Although glycemia decreased after 6 months of metformin treatment,basal and TNFα and PMA-stimulated NETs reached normal values after 12 months. Comparedto controls, nucleosomes, HNE-DNA complexes, IL-6 and TNFα levels were increasedin recently diagnosed patients and decreased after 12 months of treatment. P-selectin andvWF levels were similar in both populations.ConclusionOur data suggest that NETs could represent a biomarker for T2DM. Increased NETosis inT2DM patients does not appear to be the consequence of impaired glycemic control butrather due to pro-inflammatory cytokines and is not related to thrombotic events.