title: Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group.
abstract: BACKGROUND
  Although insulin secretion is severely decreased in most patients with type 1 diabetes, levels of residual insulin secretion often vary early in the disease. The significance of residual insulin secretion with regard to metabolic control and to long-term complications and ways to preserve such secretion are not well understood.
  
  
  OBJECTIVE
  To compare the effects of intensive and conventional therapy on residual insulin secretion in Diabetes Control and Complications Trial (DCCT) participants.
  
  
  METHODS
  Multicenter, randomized, controlled clinical trial.
  
  
  METHODS
  29 DCCT clinical centers.
  
  
  METHODS
  855 of the 1441 DCCT participants had had type 1 diabetes for 1 to 5 years at baseline. Of these 855 patients, 303 were C-peptide responders (C-peptide level, 0.20 to 0.50 pmol/mL after ingestion of a standardized, mixed meal); 138 of these patients were randomly assigned to intensive therapy, and 165 were assigned to conventional therapy. Five hundred fifty-two patients were nonresponders (stimulated C-peptide level < 0.2 pmol/mL); 274 of these patients were assigned to intensive therapy, and 278 were assigned to conventional therapy.
  
  
  METHODS
  1) Intensive therapy with 3 or more insulin injections daily or continuous subcutaneous infusion of insulin, guided by 4 or more glucose tests per day or 2) conventional therapy with 1 or 2 insulin injections daily.
  
  
  METHODS
  Stimulated C-peptide level was measured annually in responders. Development of retinopathy and microalbuminuria was assessed annually, hemoglobin A1c levels were measured quarterly, and episodes of hypoglycemia were ascertained quarterly.
  
  
  RESULTS
  Responders receiving intensive therapy maintained a higher stimulated C-peptide level and a lower likelihood of becoming nonresponders than did responders receiving conventional therapy (risk reduction, 57% [95% CI, 39% to 71%]; P < 0.001). As in the entire DCCT cohort, intensively treated responders had a reduced risk for retinopathy progression and development of microalbuminuria and a higher risk for severe hypoglycemia compared with conventionally treated responders. Among intensively treated patients, responders had a lower hemoglobin A1c value (P < 0.01), a 50% (95% CI, 12% to 72%) reduced risk for retinopathy progression, and a lower risk for severe hypoglycemia (risk reduction, 65% [CI, 53% to 74%]; P < 0.001) compared with nonresponders.
  
  
  CONCLUSIONS
  Intensive therapy for type 1 diabetes helps sustain endogenous insulin secretion, which, in turn, is associated with better metabolic control and lower risk for hypoglycemia and chronic complications. These observations underscore the importance of initiating intensive diabetic management as early as safely possible after type 1 diabetes is diagnosed.
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D013223:Statistics as Topic
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin