title: Islet autoantibody seroconversion in the DPT-1 study: justification for repeat screening throughout childhood.
abstract: OBJECTIVE
  Although type 1 diabetes autoimmunity frequently begins in childhood, little is known about the relationship between age and autoimmunity development. Our aim was to determine the timing of seroconversion to diabetes-associated autoantibody (DAA) positivity and risk in first- and second-degree relatives of patients with type 1 diabetes.
  
  
  METHODS
  Study subjects were identified through the Diabetes Prevention Trial-Type 1 (DPT-1). Children 3-18 years of age (n = 42,447) were screened for DAAs; 1,454 were ICA positive (≥ 10 JDF units), 1,758 were GAD65 positive, and 899 were ICA512 positive at the time of initial screening. Subjects who were initially antibody negative (n = 39,212) were recalled for rescreening, and 11,813 returned for rescreening.
  
  
  RESULTS
  DAA seroconversion occurred in 469 (4%) children; 258 seroconverted to ICA, 234 to GAD65, and 99 to ICA512. The median time to seroconversion was 2 years. The 2-year risk for DAAs was highest in early childhood. For each 1-year increase in age in this cohort, the risk of any autoantibody seroconversion (HR 0.95, 95% CI 0.92-0.97) decreased by 5%, and for any two autoantibodies risk decreased by 13% (0.87, 0.82-0.93).
  
  
  CONCLUSIONS
  Risk of autoantibody seroconversion among children followed in DPT-1 is age dependent. Younger children have the highest risk for DAAs, with the majority of children seroconverting by 13 years of age (75%). This suggests that annual screenings should be started in early childhood and continued through early adolescence to identify the majority of subjects at risk for type 1 diabetes and eligible for prevention trials.
authors.affiliation: Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida, USA. kendra.vehik@epi.usf.edu
authors.forename: Kendra
authors.initials: K
authors.lastname: Vehik
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Haller
authors.forename: Craig A
authors.initials: CA
authors.lastname: Beam
authors.forename: Desmond A
authors.initials: DA
authors.lastname: Schatz
authors.forename: Diane K
authors.initials: DK
authors.lastname: Wherrett
authors.forename: Jay M
authors.initials: JM
authors.lastname: Sosenko
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008403:Mass Screening; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000097:blood*; D012307:Risk Factors; D016036:Seroepidemiologic Studies
chemical_list: D001323:Autoantibodies; C024211:islet cell antibody; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2