Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany.
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3198-e3207. doi: 10.1210/clinem/dgab124.
Patients with obesity and insulin resistance are at higher risk for arterial and venous thrombosis due to a prothrombotic state.
The present study addressed whether this is reversible by lifestyle intervention and elucidated potential underlying associations.
A total of 100 individuals with impaired glucose tolerance or impaired fasting plasma glucose participated in a 1-year lifestyle intervention, including precise metabolic phenotyping and MRS-based determination of liver fat content as well as a comprehensive analysis of coagulation parameters before and after this intervention.
During the lifestyle intervention, significant reductions in coagulation factor activities (II, VII, VIII, IX, XI, and XII) were observed. Accordingly, prothrombin time (PT%) and activated partial thromboplastin time (aPTT) were slightly decreased and prolonged, respectively. Moreover, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and also protein C and protein S decreased. Fibrinogen, antithrombin, D-dimer, and FXIII remained unchanged. Searching for potential regulators, especially weight loss, but also liver fat reduction, improved insulin sensitivity, and decreased low-grade inflammation were linked to favorable changes in hemostasis parameters. Independent of weight loss, liver fat reduction (FII, protein C, protein S, PAI-1, vWF), improved insulin sensitivity (protein S, PAI-1), and reduced low-grade inflammation (PT%, aPTT, FVIII/IX/XI/XII, vWF) were identified as single potential regulators.
Lifestyle intervention is able to improve a prothrombotic state in individuals at high risk for type 2 diabetes. Besides body weight, liver fat content, insulin sensitivity, and systemic low-grade inflammation are potential mechanisms for improvements in hemostasis and could represent future therapeutic targets.
由于存在血栓形成倾向，肥胖和胰岛素抵抗的患者发生动脉和静脉血栓的风险更高。
本研究旨在探讨生活方式干预是否可以逆转这种情况，并阐明潜在的相关机制。
共有 100 名糖耐量受损或空腹血糖受损的患者参与了为期 1 年的生活方式干预，包括精确的代谢表型分析以及基于 MRS 的肝脂肪含量测定，以及在此干预前后对凝血参数进行全面分析。
在生活方式干预期间，凝血因子活性（II、VII、VIII、IX、XI 和 XII）显著降低。相应地，凝血酶原时间（PT%）和活化部分凝血活酶时间（aPTT）略有下降和延长。此外，纤溶酶原激活物抑制剂-1（PAI-1）、血管性血友病因子（vWF）以及蛋白 C 和蛋白 S 也降低。纤维蛋白原、抗凝血酶、D-二聚体和 FXIII 保持不变。寻找潜在的调节剂，特别是体重减轻，还有肝脂肪减少、胰岛素敏感性提高和低度炎症减少，与止血参数的有利变化有关。独立于体重减轻，肝脂肪减少（FII、蛋白 C、蛋白 S、PAI-1、vWF）、胰岛素敏感性改善（蛋白 S、PAI-1）和低度炎症减少（PT%、aPTT、VIII/IX/XI/XII、vWF）被确定为单个潜在的调节剂。
生活方式干预能够改善 2 型糖尿病高危人群的血栓形成倾向。除体重外，肝脂肪含量、胰岛素敏感性和全身低度炎症是改善止血的潜在机制，可能成为未来的治疗靶点。
