Prediction of type 1 diabetes among siblings of affected children and in the general population

Aims/hypothesis To compare the predictive characteristics of autoantibodies to GAD (GADA) and islet antigen 2 (IA-2A) for type 1 diabetes between siblings of affected children and children from the general population. Methods Seven-hundred and fifty-five siblings and 3,475 population-derived children were screened for GADA and IA-2A and observed for type 1 diabetes for 15 years. Sensitivity and cumulative disease risks from GADA, IA-2A and double positivity were compared between the cohorts. Results Fifty-six siblings (7.4%) tested positive for GADA, 39 (5.2%) for IA-2A and 29 (3.8%) for both autoantibodies. Thirty-four population derived participants (1.0%) had GADA, 22 (0.6%) had IA-2A and 7 (0.2%) had double positivity. Fifty-one siblings (6.8%) and 15 participants in the population cohort (0.4%) progressed to type 1 diabetes. The predictive sensitivity of GADA was 68% (95% CI 53-81%) among siblings and 50% (95% CI 23-77%) in the general population, while the corresponding values were 58 (95% CI 43-72%) and 43% (95% CI 18-71%) for IA-2A. Double-autoantibody positivity had a sensitivity of 48% (95% CI 34-63%) among siblings and 36% (95% CI 13-65%) in the population cohort. Cumulative disease risks from GADA, IA-2A and double positivity were, respectively, 61% (95% CI 48-74%), 74% (95% CI 61-88%) and 83% (95% CI 69-97%) among siblings compared with those of 24% (95% CI 9-38%), 32% (95% CI 12-51%) and 86% (95% CI 60-100%) in the general population. Conclusions/interpretation There were no significant differences in the disease-predictive sensitivity of GADA and IA-2A positivity or their combination between siblings and the population cohort, whereas, for each antibody, positivity was associated with a higher cumulative disease risk among siblings. Double-antibody positivity conferred similar cumulative disease risk both among siblings and in the general population.