evaluated the emergence of diabetes-associated autoantibodies in young children and assessed whether such antibodies could be used as surrogate markers of type I diabetes in young subjects at increased genetic risk. They studied 180 initially unaffected sibs (92 boys and 88 girls) of children with newly diagnosed type I diabetes. All sibs were younger than 6 years of age at the initial sampling, and they were monitored for the emergence of islet cell antibodies (ICA), insulin autoantibodies (IAA), glutamate decarboxylase antibodies (GADA), and IA-2 antibodies (IA-2A) up to the age of 6 years and for progression to clinical type I diabetes up to the age of 10 years. Twenty-two sibs (12.2%) tested positive for ICA in their first antibody-positive sample before the age of 6 years, 13 (7.2%) tested positive for IAA, 15 (8.3%) tested positive for GADA, and 14 (7.8%) tested positive for IA-2A. There were 16 sibs (8.9%) who had 1 detectable autoantibody, 5 (2.8%) who had 2, and 12 (6.7%) who had 3 or more. These observations suggested to that disease-associated autoantibodies could be used as surrogate markers of clinical type I diabetes in primary prevention trials targeting young subjects with increased genetic disease susceptibility.