title: The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study.
abstract: OBJECTIVE
  Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both.
  
  
  METHODS
  Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter.
  
  
  RESULTS
  Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children.
  
  
  CONCLUSIONS
  Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.
authors: Department of Pediatrics, Morsani College of Medicine, University of South Florida, 3650 Spectrum Boulevard, Suite 100, Tampa, FL, 33612, USA, jeffrey.krischer@epi.usf.edu.
authors: Jeffrey P
authors: JP
authors: Krischer
authors: Kristian F
authors: KF
authors: Lynch
authors: Desmond A
authors: DA
authors: Schatz
authors: Jorma
authors: J
authors: Ilonen
authors: Åke
authors: Å
authors: Lernmark
authors: William A
authors: WA
authors: Hagopian
authors: Marian J
authors: MJ
authors: Rewers
authors: Jin-Xiong
authors: JX
authors: She
authors: Olli G
authors: OG
authors: Simell
authors: Jorma
authors: J
authors: Toppari
authors: Anette-G
authors: AG
authors: Ziegler
authors: Beena
authors: B
authors: Akolkar
authors: Ezio
authors: E
authors: Bonifacio
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D007328:Insulin