FOR THE TRIALNET NATURAL HISTORY STUDY GROUP

OBJECTIVE—Understanding the relationship between age and islet autoantibody (Ab) sero-conversion can establish the optimal screening interval(s) to assess risk for type 1 diabetes, identify subjects who can participate in prevention trials, and determine associated costs. This study assessed the rates of seroconversion to glutamic acid decarboxylase positive (GAD65+), insulin positive (mIAA+), and insulinoma-associated protein 2 positive (ICA512+) in a large cohort of relatives of type 1 diabetes probands undergoing Ab rescreening in the TrialNet Natural History Study. RESEARCH DESIGN ANDMETHODS—Of 32,845 children aged,18 years screened for Abs, 1,287 (3.9%) were GAD65+, 778 (2.4%) were mIAA+, 677 (2.1%) were ICA512+, and 31,038 were Ab-negative. Ab-negative children were offered annual rescreening up to 18 years of age. Cox regression was used to estimate the risk for GAD65, mIAA, and ICA512 seroconversion. RESULTS—There were 205 children who seroconverted to GAD65+, 155 who seroconverted to mIAA+, and 53 who seroconverted to ICA512+ over 5.8 years of follow-up. The risk of mIAA (hazard ratio 0.89 [95 % CI 0.85–0.92]) and GAD65 (0.96 [0.93–0.99]) seroconversion signif-icantly decreased with increasing age (i.e., for each 1-year increase in age, the risk of serocon