title: NETosis before and after Hyperglycemic Control in Type 2 Diabetes Mellitus Patients.
abstract: OBJECTIVE
  Diabetes is characterized by chronic inflammation, endothelial dysfunction, increased risk of 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 diabetes mellitus (T2DM) patients. In this study, we determined whether the ability of neutrophils to form NETs differs in diabetic patients pre- and post-hyperglycemic control versus healthy donors (HD), and the relationship between NETosis with pro-thrombotic, pro-inflammatory biomarkers and thrombotic clinical events.
  
  
  METHODS
  Diabetic patients recently diagnosed and after 6 and 12 months of treatment (N = 25) and HD (N = 25) were included. NET formation was studied by microscopy and fluorometry. Nucleosomes, HNE-DNA complexes, von Willebrand factor (vWF), IL6 and TNFα plasma levels were measured by ELISA and P-selectin on the platelet surface was assessed by cytometry.
  
  
  RESULTS
  Basal levels of NETs in recently diagnosed T2DM patients were higher compared to HD. While TNFα stimulation of control neutrophils resulted in DNA release, patient neutrophils were not responsive. Although glycemia decreased after 6 months of metformin treatment, basal and TNFα and PMA-stimulated NETs reached normal values after 12 months. Compared to controls, nucleosomes, HNE-DNA complexes, IL-6 and TNFα levels were increased in recently diagnosed patients and decreased after 12 months of treatment. P-selectin and vWF levels were similar in both populations.
  
  
  CONCLUSIONS
  Our data suggest that NETs could represent a biomarker for T2DM. Increased NETosis in T2DM patients does not appear to be the consequence of impaired glycemic control but rather due to pro-inflammatory cytokines and is not related to thrombotic events.
authors.affiliation: Laboratory of Experimental Thrombosis, Institute of Experimental Medicine-CONICET-National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Agostina
authors.initials: A
authors.lastname: Carestia
authors.affiliation: Genetics and Molecular Biology, Department of Microbiology, Immunology and Biotechnology, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Frechtel
authors.affiliation: Genetics and Molecular Biology, Department of Microbiology, Immunology and Biotechnology, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Gloria
authors.initials: G
authors.lastname: Cerrone
authors.affiliation: Nutrition and Endocrinology Section, NORMED/UOM, Buenos Aires, Argentina.
authors.forename: María A
authors.initials: MA
authors.lastname: Linari
authors.affiliation: Department of Pharmacology, School of Medicine, University of Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Gonzalez
authors.affiliation: Laboratory of Experimental Thrombosis, Institute of Experimental Medicine-CONICET-National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Casais
authors.affiliation: Laboratory of Experimental Thrombosis, Institute of Experimental Medicine-CONICET-National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Mirta
authors.initials: M
authors.lastname: Schattner
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D065206:Extracellular Traps / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation / Q000453:epidemiology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D005947:Glucose