The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study

Jeffrey P. Krischer, Kristian F. Lynch, Desmond A. Schatz, Jorma Ilonen, Åke Lernmark, William A. Hagopian, Marian J. Rewers, Jin Xiong She, Olli G. Simell, Jorma Toppari, Anette G. Ziegler, Beena Akolkar, Ezio Bonifacio

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

Aims/hypothesis: 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/interpretation: Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.

Original languageEnglish (US)
Pages (from-to)980-987
Number of pages8
JournalDiabetologia
Volume58
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Autoimmunity
  • Diabetes in young children
  • HLA-DR-DQ genotypes
  • Incidence
  • Islet autoantibodies
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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