<b>Objective</b>.
Islet autoimmunity develops prior to clinical type 1 diabetes and includes multiple
and single autoantibody phenotypes. The objective was to determine age-related
risks of islet autoantibodies that reflect etiology and improve screening for
pre-symptomatic type 1 diabetes.
<p><b>Research
Design and Methods</b>. 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. </p>
<p><b>Results</b>. 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 (<i>P</i><0.0001). Risk decline was slight or absent in
single insulin- and GAD-autoantibody phenotypes. The influence of sex, <i>HLA</i> 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. </p>
<p><b>Conclusions</b>. 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. </p>
Next-Generation Sequencing Reveals ThatHLA-DRB3,-DRB4, and-DRB5May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes