title: Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.
abstract: BACKGROUND
  The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants.
  
  
  METHODS
  After the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality.
  
  
  RESULTS
  The difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.4%) and declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome than did the standard-therapy group (hazard ratio, 0.83; 95% confidence interval [CI], 0.70 to 0.99; P=0.04), with an absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years, but did not have reduced cardiovascular mortality (hazard ratio, 0.88; 95% CI, 0.64 to 1.20; P=0.42). No reduction in total mortality was evident (hazard ratio in the intensive-therapy group, 1.05; 95% CI, 0.89 to 1.25; P=0.54; median follow-up, 11.8 years).
  
  
  CONCLUSIONS
  After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. (Funded by the VA Cooperative Studies Program and others; VADT ClinicalTrials.gov number, NCT00032487.).
authors.affiliation: From the Veterans Affairs (VA) Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI (R.A.H., W.L.W.); Phoenix VA Health Care System, Phoenix, AZ (P.D.R., W.C.D.); and the Hines VA Cooperative Studies Program Coordinating Center and Edward Hines, Jr., VA Hospital (G.D.B., D.J.R., L.G., N.V.E.), and VA Pharmacy Benefits Management Services (M.M.) - all in Hines, IL.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Hayward
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
authors.forename: Wyndy L
authors.initials: WL
authors.lastname: Wiitala
authors.forename: Gideon D
authors.initials: GD
authors.lastname: Bahn
authors.forename: Domenic J
authors.initials: DJ
authors.lastname: Reda
authors.forename: Ling
authors.initials: L
authors.lastname: Ge
authors.forename: Madeline
authors.initials: M
authors.lastname: McCarren
authors.forename: William C
authors.initials: WC
authors.lastname: Duckworth
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Emanuele
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012306:Risk; D016019:Survival Analysis
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents