title: Randomized trial of insulin versus usual care in reducing restenosis after coronary intervention in patients with diabetes. the STent Restenosis And Metabolism (STREAM) study.
abstract: BACKGROUND
  Diabetes status is an independent marker of restenosis after percutaneous coronary intervention (PCI). Previous studies suggest that metabolic abnormalities associated with diabetes increase stent restenosis by promoting intimal hyperplasia. Preclinical studies have indicated that insulin therapy reduces intimal hyperplasia. The objective of this study was to determine whether insulin-mediated glucose lowering reduces in-stent restenosis in patients with diabetes undergoing PCIs.
  
  
  METHODS
  We conducted a prospective, randomized, multicenter, open-labeled study with blinded outcomes. Patients were randomized 1:1 to daily bedtime subcutaneous NPH insulin (Novo Nordisk) versus usual therapy with oral hypoglycemic agents. The main outcomes were change in volume of intimal hyperplasia within the stent measured by intravascular ultrasound and late lumen loss by quantitative coronary angiography at 6 months post-PCI.
  
  
  RESULTS
  Seventy-eight patients (36 insulin, 42 usual care) were randomized. Eight patients in each group received drug-eluting stents. The insulin group achieved greater reductions in both glycosylated hemoglobin A1c (mean±S.D.) (insulin: 8.0%±1.2% to 6.7%±0.7% vs. control: 7.5%±1.2% to 7.1%±1.0 %, P=.0038) and fasting glucose (insulin: 9.3±3.8 to 5.8±1.7 vs. usual care: 8.4±2.4 to 7.7±2.0 mmol/l, P<.0001). There were no hypoglycemic events. At 6 months, there were no significant differences in either intravascular-ultrasound-determined neointimal volume (insulin: 41.2±38.9 vs. usual care: 48.4±40.2 mm(3), P=.33) or late lumen loss by angiography (insulin: 1.29±0.74 mm vs. usual care: 1.02±0.71 mm, P=.17).
  
  
  CONCLUSIONS
  Addition of a single bedtime dose of insulin in patients with diabetes does not influence in-stent restenosis.
authors.affiliation: Division of Cardiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada. nataraja@mcmaster.ca
authors.forename: Madhu K
authors.initials: MK
authors.lastname: Natarajan
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Strauss
authors.forename: Michael
authors.initials: M
authors.lastname: Rokoss
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Buller
authors.forename: G B John
authors.initials: GB
authors.lastname: Mancini
authors.forename: Changchun
authors.initials: C
authors.lastname: Xie
authors.forename: Tej N
authors.initials: TN
authors.lastname: Sheth
authors.forename: David
authors.initials: D
authors.lastname: Goodhart
authors.forename: Eric A
authors.initials: EA
authors.lastname: Cohen
authors.forename: Peter
authors.initials: P
authors.lastname: Seidelin
authors.forename: William
authors.initials: W
authors.lastname: Harper
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D001786:Blood Glucose / Q000378:metabolism; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D017211:Treatment Failure; D018084:Ultrasonography, Interventional
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007336:Insulin, Isophane