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

Author:
  • 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
Publishing year: 2015
Language: English
Pages: 980-987
Publication/Series: Diabetologia
Volume: 58
Issue: 5
Document type: Journal article
Publisher: Springer

Abstract english

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.

Keywords

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

Other

Published
  • Diabetes and Celiac Unit
  • ISSN: 1432-0428
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00