title: Age of islet autoantibody appearance and mean levels of insulin, but not GAD or IA-2 autoantibodies, predict age of diagnosis of type 1 diabetes: diabetes autoimmunity study in the young.
abstract: OBJECTIVE
  We evaluated predictors of progression to diabetes in children with high-risk HLA genotypes and persistent islet autoantibodies.
  
  
  METHODS
  The Diabetes Autoimmunity Study in the Young (DAISY) followed 2,542 children with autoantibodies measured to GAD, IA-2, and insulin.
  
  
  RESULTS
  Persistent islet autoantibodies developed in 169 subjects, and 55 of those progressed to diabetes. Children expressing three autoantibodies showed a linear progression to diabetes with 74% cumulative incidence by the 10-year follow-up compared with 70% with two antibodies and 15% with one antibody (P < 0.0001). Both age of appearance of first autoantibody and insulin autoantibody (IAA) levels, but not GAD or IA-2 autoantibodies, were major determinants of the age of diabetes diagnosis (r = 0.79, P < 0.0001).
  
  
  CONCLUSIONS
  In the DAISY cohort, 89% of children who progressed to diabetes expressed two or more autoantibodies. Age of diagnosis of diabetes is strongly correlated with age of appearance of first autoantibody and IAA levels.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA. andrea.steck@ucdenver.edu
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Steck
authors.forename: Kelly
authors.initials: K
authors.lastname: Johnson
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Barriga
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: John C
authors.initials: JC
authors.lastname: Hutton
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Rewers
mesh_terms: D017668:Age of Onset; D001323:Autoantibodies / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D007328:Insulin; D007330:Insulin Antibodies; D007515:Islets of Langerhans / Q000276:immunology; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; D007328:Insulin; D007330:Insulin Antibodies; D005968:Glutamate Decarboxylase