title: Profibrinolytic, antithrombotic, and antiinflammatory effects of an insulin-sensitizing strategy in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.
abstract: BACKGROUND
  Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial of 2 mechanistically different strategies for treatment of hyperglycemia, insulin-sensitizing and insulin-providing strategies, on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy.
  
  
  RESULTS
  A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years. Plasminogen activator inhibitor type 1 antigen and activity, tissue plasminogen activator antigen, fibrinogen, D-dimer, C-reactive protein, insulin, and hemoglobin A(1c) were assayed in blood samples acquired at baseline and at 12 regular intervals throughout the follow-up interval. Higher baseline D-dimer, fibrinogen, and C-reactive protein portended a poor prognosis in patients in both groups. In contrast to the insulin-providing strategy, the insulin-sensitizing strategy led to (1) lower plasma insulin; (2) lower plasminogen activator inhibitor type 1 antigen and activity and lower tissue plasminogen activator antigen (known to track with plasminogen activator inhibitor type 1); and (3) lower C-reactive protein and fibrinogen at all intervals after baseline (P<0.001 for each).
  
  
  CONCLUSIONS
  The insulin-sensitizing treatment strategy led to changes in biomarker profiles indicative of decreased insulin resistance, an altered balance between thrombosis and fibrinolysis favoring fibrinolysis, and diminished intensity of the systemic inflammatory state, factors that have been associated with cardiovascular risk.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00006305.
authors.affiliation: Cardiovascular Research Institute, University of Vermont, Colchester Research Facility, Colchester, VT 05446, USA. Burton.Sobel@uvm.edu
authors.forename: Burton E
authors.initials: BE
authors.lastname: Sobel
authors.forename: Regina M
authors.initials: RM
authors.lastname: Hardison
authors.forename: Saul
authors.initials: S
authors.lastname: Genuth
authors.forename: Maria M
authors.initials: MM
authors.lastname: Brooks
authors.forename: Robert D
authors.initials: RD
authors.lastname: McBane
authors.forename: David J
authors.initials: DJ
authors.lastname: Schneider
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Robert
authors.initials: R
authors.lastname: Wolk
authors.forename: Ashok
authors.initials: A
authors.lastname: Krishnaswami
authors.forename: Robert L
authors.initials: RL
authors.lastname: Frye
mesh_terms: D000328:Adult; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation; D007328:Insulin / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use; D007333:Insulin Resistance; D053208:Kaplan-Meier Estimate; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009204:Myocardial Revascularization; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011379:Prognosis; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use; D019851:Thrombophilia / Q000097:blood* / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000032:analysis
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D017395:Plasminogen Activator Inhibitor 1; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D010959:Tissue Plasminogen Activator; C051321:SERPINE1 protein, human; C036309:fibrin fragment D; C089946:2,4-thiazolidinedione