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.
Funded by NIH, NIDDK, NIAID, NICHD, NIEHS, JDRF and CDC.