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Åke Lernmark

Principal investigator

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Reversion of β-cell autoimmunity changes risk of type 1 diabetes : TEDDY study

Author

  • Kendra Vehik
  • Kristian F. Lynch
  • Desmond A. Schatz
  • Beena Akolkar
  • William Hagopian
  • Marian Rewers
  • Jin Xiong She
  • Olli Simell
  • Jorma Toppari
  • Anette G. Ziegle
  • Åke Lernmark
  • Ezio Bonifacio
  • Jeffrey P. Krischer

Summary, in English

OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS Reversion was relatively frequent for autoantibodies to GAD65 (19%) and insulin (29%), but was largely restricted to children who had single autoantibodies (24%) and rare in children who had developed multiple autoantibodies (<1%). Most (85%) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.

Department/s

  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2016-09-01

Language

English

Pages

1535-1542

Publication/Series

Diabetes Care

Volume

39

Issue

9

Document type

Journal article

Publisher

American Diabetes Association

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 0149-5992