title: Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes.
abstract: OBJECTIVE
  Seroconversion to islet autoantibodies precedes type 1 diabetes. This study aimed to identify periods of high seroconversion incidence, which could be targeted for mechanistic and therapeutic studies.
  
  
  METHODS
  Incidence of islet autoantibodies was calculated in 1,650 genetically at-risk children followed with measurements of islet autoantibodies and thyroid autoantibodies at age 9 months and 2, 5, 8, 11, 14 and 17 years. Peak incidence periods were confirmed in a second cohort of 150 children followed until age 6 years with three-monthly samples up to age 3 years.
  
  
  RESULTS
  Islet autoantibody incidence (per 1,000 person-years) was 18.5 until age 9 months, 21 from 9 months to 2 years and <10 for intervals after age 2 years. The second cohort confirmed peak incidence around age 9 months and demonstrated an absence of seroconversion before this age. Seroconversion to insulin autoantibodies occurred earlier than other autoantibodies (p<0.01 against glutamic acid decarboxylase [GAD]-, insulinoma-associated protein 2 [IA-2]- and zinc transporter 8 [ZnT8]-autoantibodies). Early peak seroconversion incidence was most evident in children with high-risk HLA DR3/4-DQ8 or DR4/4-DQ8 genotypes.
  
  
  CONCLUSIONS
  The age period 9 months to 2 years is associated with a high incidence of activation of type 1 diabetes associated autoimmunity in genetically at-risk children and should be targeted for effective primary prevention strategies.
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany. anette-g.ziegler@helmholtz-muenchen.de
authors.forename: A-G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002648:Child; D016241:Child of Impaired Parents; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D016133:Polymerase Chain Reaction; D011236:Prediabetic State / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006681:HLA-D Antigens