title: Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY).
abstract: OBJECTIVE
  While it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined.
  
  
  METHODS
  The Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months.
  
  
  RESULTS
  Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes.
  
  
  CONCLUSIONS
  In the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.
authors: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO andrea.steck@ucdenver.edu.
authors: Andrea K
authors: AK
authors: Steck
authors: Pediatric Epidemiology Center, University of South Florida, Tampa, FL.
authors: Kendra
authors: K
authors: Vehik
authors: Technische Universität Dresden, Dresden, Germany.
authors: Ezio
authors: E
authors: Bonifacio
authors: Lund University/Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors: Ake
authors: A
authors: Lernmark
authors: Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany; Klinikum rechts der Isar, Technische Universität München, München, Germany; and Forschergruppe Diabetes e.V., Neuherberg, Germany.
authors: Anette-G
authors: AG
authors: Ziegler
authors: Pacific Northwest Diabetes Research Institute, Seattle, WA.
authors: William A
authors: WA
authors: Hagopian
authors: Medical College of Georgia, Georgia Regents University, Augusta, GA.
authors: JinXiong
authors: J
authors: She
authors: Department of Pediatrics, University of Turku, Turku, Finland.
authors: Olli
authors: O
authors: Simell
authors: Division of Diabetes, Endocrinology, & Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors: Beena
authors: B
authors: Akolkar
authors: Pediatric Epidemiology Center, University of South Florida, Tampa, FL.
authors: Jeffrey
authors: J
authors: Krischer
authors: University of Florida, Gainesville, FL.
authors: Desmond
authors: D
authors: Schatz
authors: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO.
authors: Marian J
authors: MJ
authors: Rewers
mesh_terms: D001323:Autoantibodies / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D007330:Insulin Antibodies / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology*; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007330:Insulin Antibodies; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase