Development of autoantibodies in the TrialNet natural history study

Abstract

OBJECTIVE - Understanding the relationship between age and islet autoantibody (Ab) seroconversion 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 AND METHODS - 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 significantly decreased with increasing age (i.e., for each 1-year increase in age, the risk of seroconversion decreased by 11% [P < 0.0001] for mIAA and 4% [P = 0.04] for GAD65) across all ages. The cumulative Ab seroconversion was 2% for those <10 years of age versus 0.7% for those ≥10 years of age. CONCLUSIONS - The risk of development of islet Abs declines with increasing age in type 1 diabetes relatives. These data support annual screening for children <10 years of age and one additional screening in adolescence. © 2011 by the American Diabetes Association.