Prediction of Type 1 Diabetes in the General Population

OBJECTIVE - To evaluate the utility of GAD antibodies (GADAs) and islet antigen-2 antibodies (1A-2As) in prediction of type 1 diabetes over 27 years in the general population and to assess the 6-year rates of seroconversion. RESEARCH DESIGN AND METHODS - A total of 3,475 nondiabetic subjects aged 3-18 years were sampled in 1.980, and 2,375 subjects (68.3%) were resampled in 1986. All subjects were observed for development of diabetes to the end of 2007. GADAs and 1A-2As were analyzed in all samples obtained in 1980 and 1986. RESULTS - A total of 34 individuals (1.0%; 9 developed diabetes) initially had GADAs and 22 (0.6%; 9 developed diabetes) 1A-2As. Seven subjects (0.2%) tested positive for both autoantibodies. The positive seroconversion rate over 6 years was 0.4% for GADAs and 0.2% for 1A-2As, while the inverse seroconversion rates were 33 and 57%, respectively. Eighteen subjects (0.5%) developed type 1 diabetes after a median pre-diabetic period of 8.6 years (range 0.9-20.3). Initial positivity for GADAs and/or 1A-2As had a sensitivity of 61% (95% CI 36-83) for type 1. diabetes. Combined positivity for GADAs and 1A-2As had both a specificity and a positive predictive value of 100% (95% CI 59-100). CONCLUSIONS - One-time screening for GADAs and 1A-2As in the general childhood population in Finland would identify similar to 60% of those individuals who will develop type 1. diabetes over the next 27 years, and those subjects who have both autoantibodies carry an extremely high risk for diabetes. Both positive and inverse seroconversions do occur over time reflecting a dynamic process of beta-cell autoimmunity.