An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood
Research Design and Methods. The Environmental Determinants of Diabetes in the Young study prospectively followed 8,556 genetically at-risk children at 3–6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models.
Results. The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% confidence interval, 3.8–4.7) at 7.5 months of age and declined to 1.1% (95% confidence interval, 0.8–1.3) at a landmark age of 6.25 years (P<0.0001). Risk decline was slight or absent in single insulin- and GAD-autoantibody phenotypes. The influence of sex, HLA and other susceptibility genes on risk subsided with increasing age and was abrogated by age six years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5–7 years of age.
Conclusions. The risk of developing islet autoimmunity declines exponentially with age and the influence of major genetic factors on this risk is limited to the first few years of life.