We analyzed demographic and genetic differences between children with various diabetes-associated autoantibodies reflecting the autoimmune process. In a prospective birth cohort comprising children with HLA-conferred susceptibility to type 1 diabetes (T1D) the pattern of autoantibody appearance was analyzed in 520 children with advanced β-cell autoimmunity associated with high disease risk. In 315 cases a single biochemical autoantibody could be identified in the first positive sample, to insulin (IAA) in 180, to GAD (GADA) in 107 and to islet antigen-2 (IA-2A) in 28. The age at seroconversion differed significantly between the three groups (P=0.003). IAA as the first autoantibody showed a peak of appearance during the second year of life, whereas GADA as the first autoantibody peaked later between age 3 to 5. The risk associated insulin gene rs689 AA genotypes were more frequent in children with IAA as the first autoantibody compared to the other children (P=0.002). The primary autoantigen in the development of β-cell autoimmunity and T1D seems to strongly correlate with age and genetic factors indicating heterogeneity in the initiation of the disease process.
- Received February 21, 2013.
- Accepted June 19, 2013.
- © 2013 by the American Diabetes Association.
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