1. Predictors of neutrophil extracellular traps markers in type 2 diabetes mellitus: associations with a prothrombotic state and hypofibrinolysis.
- Author
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Bryk AH, Prior SM, Plens K, Konieczynska M, Hohendorff J, Malecki MT, Butenas S, and Undas A
- Subjects
- Aged, Biomarkers blood, Blood Glucose metabolism, Cell-Free Nucleic Acids blood, Citrullination, Cross-Sectional Studies, DNA blood, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis, Female, Glycated Hemoglobin metabolism, Histones blood, Humans, Inflammation Mediators blood, Leukocyte Elastase blood, Male, Middle Aged, Peroxidase blood, Risk Factors, Thrombin metabolism, Thrombosis diagnosis, Thrombosis etiology, Diabetes Mellitus, Type 2 blood, Extracellular Traps metabolism, Fibrinolysis, Thrombosis blood
- Abstract
Background: Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM., Methods: In a cross-sectional study involving 113 T2DM patients aged 63.7 ± 8.2 years, we investigated citrullinated histone H3 (H3Cit), cell-free deoxyribonucleic acid (cfDNA), myeloperoxidase, neutrophil elastase, and inflammation markers, along with thrombin generation (TG), plasma clot lysis time (CLT), clot permeability (K
s ) and fibrinolysis inhibitors., Results: On multivariate logistic regression analysis adjusted for age and gender, predictors of high H3Cit (≥ 7.36 ng/mL, upper quartile) were: glycated hemoglobin (HbA1c) ≥ 7.0% and interleukin-6. Interleukin-6 was also found to be a predictor of high cfDNA (≥ 2.84 µg/mL, upper quartile) along with glucose. Citrullinated histone H3 and cfDNA correlated positively with CLT and inversely with Ks , while TG associated solely with cfDNA. These associations were not seen with myeloperoxidase and neutrophil elastase. Patients with previous myocardial infarction (n = 21, 18.6%) had higher H3Cit (+108%, p < 0.001) and cfDNA (+45%, p = 0.022). On multivariable analysis adjusted for potential confounders, H3Cit and cfDNA, along with plasminogen activator inhibitor-1 and concomitant cardiovascular disease, were predictors of CLT. Citrullinated histone H3 alone was a predictor of Ks and only cfDNA was a predictor of peak thrombin generated., Conclusions: In T2DM, NETosis detectable in circulating blood is associated with inflammatory state and a prothrombotic state, especially hypofibrinolysis.- Published
- 2019
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