title: Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis.
abstract: 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.
authors.affiliation: Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, Umeå, Sweden.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Eriksson
authors.forename: Eva
authors.initials: E
authors.lastname: Rask
authors.forename: Owe
authors.initials: O
authors.lastname: Johnson
authors.forename: Kjell
authors.initials: K
authors.lastname: Carlström
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Mats
authors.initials: M
authors.lastname: Eliasson
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderberg
mesh_terms: D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D010959:Tissue Plasminogen Activator