Eriksson Maria A, Rask Eva, Johnson Owe, Carlström Kjell, Ahrén Bo, Eliasson Mats, Boman Kurt, Söderberg Stefan
Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, Umeå, Sweden.
Blood Coagul Fibrinolysis. 2008 Oct;19(7):625-32. doi: 10.1097/MBC.0b013e3283099046.
The adipocyte-derived hormone leptin is associated with insulin resistance and reduced fibrinolytic status--or dysfibrinolysis--in humans. As leptin associates differentially to the development of cardiovascular disease and diabetes in men and women, we hypothesized that leptin and insulin sensitivity are related to dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were recruited from the Monitoring of trends and determinants in Cardiovascular disease (MONICA) population sample, representing the highest and lowest quartiles of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding globulin were measured. Insulin sensitivity was estimated using the euglycaemic clamp technique. Body composition was determined by bioimpedance. Determinants for circulating levels of fibrinolytic factors were explored in a multivariate linear regression analysis. Levels of fibrinolytic variables and estimated insulin sensitivity did not differ between men and women. Leptin was independently associated with reduced fibrinolytic status (high PAI-1 activity, low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P < 0.001-0.002). In women, fat mass and/or insulin sensitivity were related to these factors (P < 0.001-0.03), and leptin only to reduced tPA activity (P = 0.002). Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate differentially in men and women.
脂肪细胞分泌的激素瘦素与人类的胰岛素抵抗及纤溶状态降低（即纤溶异常）有关。由于瘦素在男性和女性心血管疾病及糖尿病的发生发展过程中的关联存在差异，我们推测瘦素与胰岛素敏感性和纤溶异常之间存在性别依赖性关系。从心血管疾病趋势和决定因素监测（MONICA）人群样本中招募了32名男性和40名女性，这些样本代表空腹胰岛素水平的最高和最低四分位数。测量了血脂、纤溶状态[纤溶酶原激活物抑制剂1（PAI-1）活性、组织纤溶酶原激活物（tPA）质量和活性以及tPA-PAI复合物]、瘦素、睾酮和性激素结合球蛋白。使用正常血糖钳夹技术评估胰岛素敏感性。通过生物电阻抗测定身体成分。在多变量线性回归分析中探讨了纤溶因子循环水平的决定因素。男性和女性之间纤溶变量水平和估计的胰岛素敏感性没有差异。在男性中，瘦素与纤溶状态降低（高PAI-1活性、低tPA活性、高tPA质量和高tPA-PAI复合物）独立相关（P<0.001-0.002）。在女性中，脂肪量和/或胰岛素敏感性与这些因素相关（P<0.001-0.03），而瘦素仅与降低的tPA活性相关（P=0.002）。高瘦素血症、纤溶异常、胰岛素敏感性和雄激素性在男性和女性中的关联存在差异。
