title: Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality.
abstract: OBJECTIVE
  Whether mortality in type 1 diabetes mellitus is affected following intensive glycemic therapy has not been established.
  
  
  OBJECTIVE
  To determine whether mortality differed between the original intensive and conventional treatment groups in the long-term follow-up of the Diabetes Control and Complications Trial (DCCT) cohort.
  
  
  METHODS
  After the DCCT (1983-1993) ended, participants were followed up in a multisite (27 US and Canadian academic clinical centers) observational study (Epidemiology of Diabetes Control and Complications [EDIC]) until December 31, 2012. Participants were 1441 healthy volunteers with diabetes mellitus who, at baseline, were 13 to 39 years of age with 1 to 15 years of diabetes duration and no or early microvascular complications, and without hypertension, preexisting cardiovascular disease, or other potentially life-threatening disease.
  During the clinical trial, participants were randomly assigned to receive intensive therapy (n = 711) aimed at achieving glycemia as close to the nondiabetic range as safely possible, or conventional therapy (n = 730) with the goal of avoiding symptomatic hypoglycemia and hyperglycemia. At the end of the DCCT, after a mean of 6.5 years, intensive therapy was taught and recommended to all participants and diabetes care was returned to personal physicians.
  
  
  METHODS
  Total and cause-specific mortality was assessed through annual contact with family and friends and through records over 27 years' mean follow-up.
  
  
  RESULTS
  Vital status was ascertained for 1429 (99.2%) participants. There were 107 deaths, 64 in the conventional and 43 in the intensive group. The absolute risk difference was -109 per 100,000 patient-years (95% CI, -218 to -1), with lower all-cause mortality risk in the intensive therapy group (hazard ratio [HR] = 0.67 [95% CI, 0.46-0.99]; P = .045). Primary causes of death were cardiovascular disease (24 deaths; 22.4%), cancer (21 deaths; 19.6%), acute diabetes complications (19 deaths; 17.8%), and accidents or suicide (18 deaths; 16.8%). Higher levels of glycated hemoglobin (HbA1c) were associated with all-cause mortality (HR = 1.56 [95% CI, 1.35-1.81 per 10% relative increase in HbA1c]; P < .001), as well as the development of albuminuria (HR = 2.20 [95% CI, 1.46-3.31]; P < .001).
  
  
  CONCLUSIONS
  After a mean of 27 years' follow-up of patients with type 1 diabetes, 6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause mortality rate when compared with conventional therapy.
  
  
  BACKGROUND
  clinicaltrials.gov Identifiers: NCT00360815 and NCT00360893.
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: David M
authors.initials: DM
authors.lastname: Nathan
authors.affiliation: Lunefeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: The George Washington University Biostatistics Center, Rockville, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cleary
authors.affiliation: Cornell University Medical Center, New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: Brillon
authors.affiliation: The George Washington University Biostatistics Center, Rockville, Maryland.
authors.forename: Jye-Yu C
authors.initials: JY
authors.lastname: Backlund
authors.affiliation: The George Washington University Biostatistics Center, Rockville, Maryland.
authors.forename: John M
authors.initials: JM
authors.lastname: Lachin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D001786:Blood Glucose; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006943:Hyperglycemia / Q000188:drug therapy / Q000209:etiology; D007003:Hypoglycemia / Q000188:drug therapy / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D009369:Neoplasms / Q000401:mortality; D013405:Suicide / Q000706:statistics & numerical data
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents