Oral Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Febrile respiratory infections are associated with increased risk of islet autoimmunity in the TEDDY study (#27)

Maria Lonnrot 1 , Kristian Lynch 2 , Helena Larsson 3 , Åke Lernmark 3 , Marian Rewers 4 , Carina Torn 3 , Brant Burkhart 2 , Thomas Briese 5 , William Hagopian 6 , Jin-Xiong She 7 , Olli Simell 8 , Anette Ziegler 9 , Beena Akolkar 10 , Jeffrey Krischer 2 , Heikki Hyoty 11 , Teddy Study Group 12
  1. Tampere University and Seinäjoki Central Hospital, Tampere and Seinäjoki, Finland
  2. University of South Florida, Tampa, USA
  3. Lund University, Malmö, Sweden
  4. Barbara Davis Center for Childhood Diabetes, Colorado, USA
  5. Columbia University, New York, USA
  6. Pacific Northwest Diabetes Research Institute, Seattle, USA
  7. Medical College of Georgia, Atlanta, USA
  8. University of Turku, Turku, Finland
  9. Diabetes Research Institute, Munich, Germany
  10. NIH, Bethesda, USA
  11. University of Tampere, Tampere, Finland
  12. TEDDY investigators, USA, Germany, Sweden and Finland

Microbial infections may play a role in the etiology and pathogenesis of type 1 diabetes (T1D). Depending on a child’s age, different microbes may have varying effects. The lag period between infection and islet autoimmunity may vary from one microbe to another. The present study evaluated time varying associations between reported infections and appearance of islet autoantibodies (IA) in children who were prospectively followed from birth.


TEDDY study is a prospective birth cohort study following 8502 children with T1D-associated HLA-DQ genotypes from Finland, Germany, Sweden and US. IA (IAA, GADA, IA-2A) are measured quarterly through the first 4 years of life and semiannually thereafter. Infections and fever episodes are recorded by detailed questionnaires collected every 3 months during the follow-up.


Persistent confirmed IA have developed in 442 children before the age of 48 months. Febrile respiratory infections were associated with increased risk of developing IA. This association was strongly time-dependent with increased risk of IA appearance only within the immediate three month period following the period of infection (HR=1.4, 95% CI=1.1–1.7; p=0.001). Non-febrile respiratory infections, gastrointestinal infections or the average number of infections during the follow-up were not associated with IA.


The close time-relationship between febrile respiratory infections and the appearance of IA suggests that certain respiratory pathogens may trigger islet autoimmunity. Further studies are in progress to identify these microbes using comprehensive laboratory testing of the samples collected from the TEDDY children.