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Hemostatic alterations linked to body fat distribution, fatty liver and insulin resistance.
Mol. Metab. 53:101262 (2021)
OBJECTIVE: Obesity, in particular visceral obesity, and insulin resistance emerged as major risk factors for severe Coronavirus Disease 2019 (COVID-19), which is strongly associated with hemostatic alterations. Since obesity and insulin resistance predispose to thrombotic diseases, we investigated the relationship between hemostatic alterations and body fat distribution in subjects at risk for type 2 diabetes. SUBJECTS AND METHODS: Body fat distribution (visceral and subcutaneous abdominal adipose tissue) and liver fat content of 150 subjects with impaired glucose tolerance and/or impaired fasting glucose was determined using magnetic resonance imaging and spectroscopy. Participants underwent precise metabolic characterization and major hemostasis parameters were analyzed. RESULTS: Procoagulant factors (FII, FVII, FVIII and FIX) and anticoagulant proteins (antithrombin, protein C and protein S) were significantly associated with body fat distribution. In subjects with fatty liver, fibrinogen (298 mg/dl vs. 264 mg/dl, p=0.0182), FVII (99% vs. 90%, p=0.0049), FVIII (114% vs. 90 %, p=0.0098), protein C (124% vs. 111%, p=0.0006) and protein S (109% vs. 89%, p<0.0001) were higher than in controls. In contrast, antithrombin (97% vs. 102%, p=0.0025) was higher in control subjects. In multivariate analyses controlling for insulin sensitivity, body fat compartments and genotype variants (PNPLA3I148MM/MI/TM6SF2E167KK/KE), only protein C and protein S remained significantly increased in fatty liver. CONCLUSIONS: Body fat distribution is significantly associated with alterations of procoagulant as well as anticoagulant parameters. Liver fat plays a key role for the regulation of protein C and protein S suggesting a potential counteracting mechanism to the prothrombotic state in subjects with prediabetes and fatty liver.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Body Fat Distribution ; Abdominal Obesity ; Coagulation ; Liver Fat ; Prediabetes; Protein-c Levels; Adipose-tissue; Confers Susceptibility; Linking Obesity; Factor-viii; Risk; Coagulation; Association; Sensitivity; Topography
ISSN (print) / ISBN
2212-8778
e-ISSN
2212-8778
Journal
Molecular Metabolism
Quellenangaben
Volume: 53,
Article Number: 101262
Publisher
Elsevier
Publishing Place
Amsterdam
Non-patent literature
Publications
Reviewing status
Peer reviewed
Grants
German Center for Diabetes Research (DZD) - German Federal Ministry for Education and Research