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Hörber, S. ; Lehmann, R. ; Stefan, N. ; Machann, J. ; Birkenfeld, A.L. ; Wagner, R. ; Heni, M. ; Häring, H.-U. ; Fritsche, A. ; Peter, A.

Hemostatic alterations linked to body fat distribution, fatty liver and insulin resistance.

Mol. Metab. 53:101262 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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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
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Journal Molecular Metabolism
Quellenangaben Volume: 53, Issue: , Pages: , Article Number: 101262 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502400-001
Grants German Center for Diabetes Research (DZD) - German Federal Ministry for Education and Research
DOI 10.1016/j.molmet.2021.101262
WOS ID WOS:000705547500009
Scopus ID 85109463670
PubMed ID 34082137
Erfassungsdatum 2021-07-06
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