title: Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes.
abstract: OBJECTIVE
  A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes.
  
  
  METHODS
  The design was an individually matched case-control study of all Danish type 1 diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004 (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5 days after birth in the 1981-2002 birth cohorts and stored at -25 °C were identified from 2023 patients and from two matched controls (n = 4042). Birth data and information on parental age and diabetes were obtained from Danish registers. GAD65A and IA-2A were determined in a radiobinding assay. HLA-DQB1 alleles were analyzed by PCR using time-resolved fluorescence.
  
  
  RESULTS
  GAD65A and IA-2A were found in 70/2023 (3.5%) patients compared to 21/4042 (0.5%) controls resulting in a hazard ratio (HR) of 7.49 (P < 0.0001). The HR decreased to 4.55 but remained significant (P < 0.0003) after controlling for parental diabetes and HLA-DQB1 alleles. Conditional logistic regression analysis showed a HR of 2.55 (P < 0.0001) for every tenfold increase in the levels of GAD65A and IA-2A. This HR decreased to 1.93 but remained significant (P < 0.001) after controlling for parental diabetes and HLA-DQB1 alleles.
  
  
  CONCLUSIONS
  These data suggest that GAD65A and IA-2A positivity at birth are associated with an increased risk of developing type 1 diabetes in Danish children diagnosed between 1981 and 2004.
authors.affiliation: Hagedorn Research Institute and Steno Diabetes Center, DK-2828 Gentofte, Denmark.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eising
authors.forename: Anita
authors.initials: A
authors.lastname: Nilsson
authors.forename: Bendix
authors.initials: B
authors.lastname: Carstensen
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.forename: Bent
authors.initials: B
authors.lastname: Nørgaard-Pedersen
authors.forename: Jørn
authors.initials: J
authors.lastname: Nerup
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
mesh_terms: D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007223:Infant; D016015:Logistic Models; D016133:Polymerase Chain Reaction; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics / Q000276:immunology*; D012306:Risk; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2