title: Gender-specific alterations in fibrin structure function in type 2 diabetes: associations with cardiometabolic and vascular markers.
abstract: BACKGROUND
  Diabetes is associated with increased incidence of atherothrombotic disease. The fibrin network forms the backbone of the arterial thrombus, and fibrin clot structure determines predisposition to cardiovascular events.
  
  
  OBJECTIVE
  The aim of the study was to investigate fibrin clot structure/fibrinolysis in the largest type 2 diabetes cohort and analyze associations with cardiometabolic risk factors and vascular pathology.
  
  
  METHODS
  Clot structure/fibrinolysis was assessed in 875 participants of the Edinburgh Type 2 Diabetes Study [age, 68 (range, 60-75) yr; 450 males] by turbidimetric assays, and clots were visualized by confocal microscopy. Four parameters of clot structure/fibrinolysis were analyzed, and plasma levels of fibrinogen and plasminogen activator inhibitor-1 were studied by Clauss assay and ELISA, respectively.
  
  
  RESULTS
  Clot maximum absorbance was increased in females compared with males (0.37 ± 0.005 and 0.34 ± 0.005 arbitrary unit, respectively; P < 0.001), and took longer to lyse (803 ± 20 and 665 ± 12 sec, respectively; P < 0.001). These gender differences in clot structure and fibrinolysis were still evident after correcting for fibrinogen and plasminogen activator inhibitor-1 plasma levels. A prothrombotic fibrin structure profile was associated with increased body mass index and low levels of high-density lipoprotein in women and with inadequate diabetes control in men. Clot formation time was related to previous cardiac ischemic events in both men and women after adjusting for traditional risk factors [odds ratio, 1.22 (95% confidence interval, 1.07, 1.38); and 1.33 (1.15, 1.50), respectively], and prothrombotic clots were associated with low ankle brachial index, renal impairment, and smoking, regardless of gender.
  
  
  CONCLUSIONS
  Women with type 2 diabetes have compact clots with compromised fibrinolysis compared with men. There are gender-specific associations between clotting parameters and cardiometabolic risk factors in this population, whereas vascular abnormalities, impaired renal function, and smoking are associated with prothrombotic clot structure profile regardless of gender.
authors.affiliation: Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: Saad H
authors.initials: SH
authors.lastname: Alzahrani
authors.forename: Katharina
authors.initials: K
authors.lastname: Hess
authors.forename: Jackie F
authors.initials: JF
authors.lastname: Price
authors.forename: Mark
authors.initials: M
authors.lastname: Strachan
authors.forename: Paul D
authors.initials: PD
authors.lastname: Baxter
authors.forename: Richard
authors.initials: R
authors.lastname: Cubbon
authors.forename: Fladia
authors.initials: F
authors.lastname: Phoenix
authors.forename: T
authors.initials: T
authors.lastname: Gamlen
authors.forename: R A S
authors.initials: RA
authors.lastname: Ariëns
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grant
authors.forename: Ramzi A
authors.initials: RA
authors.lastname: Ajjan
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology*; D001780:Blood Coagulation Tests; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D005260:Female; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D013329:Structure-Activity Relationship
chemical_list: D015415:Biomarkers; D005337:Fibrin