Interaction of Onset and Duration of Diabetes on the Percent of GAD and IA-2 Antibody-Positive Subjects in the Type 1 Diabetes Genetics Consortium Database

OBJECTIVE: GAD antibodies (GADA) are more common in type 1 diabetic subjects diagnosed at an older age, whereas insulinoma-antigen 2 antibodies (IA-2A) are more common in subjects with younger onset. The prevalence of both antibodies decreases with longer duration of type 1 diabetes. We evaluated the interaction between age of diagnosis (onset) and duration of diabetes on the percentage of GADA- and IA-2A-positive subjects. RESEARCH DESIGN AND METHODS: Data were used from 5,020 individuals with type 1 diabetes obtained from the Type 1 Diabetes Genetics Consortium dataset. The percentages of GADA- and IA-2A-positive subjects were modeled with duration as the continuous independent variable using a modified spline. RESULTS: Within the first 5 years from diagnosis, 19.4% of individuals (median age 13 years) had neither GADA nor IA-2A, and by 6 to 13 years after diagnosis (median age 18 years), 31.7% were antibody-negative. There was no significant interaction between onset of disease and duration of diabetes for IA-2A (P = 0.30). The interaction was significant for GADA (P = 0.0002), resulting from differences in subjects diagnosed at or older than age 14. For these individuals, there was no apparent effect of duration of disease on the percentage of GADA-positive subjects within the first 5 years of diagnosis. CONCLUSIONS: Onset and duration of diabetes both have an important effect on antibody status. The interaction of onset and duration on GADA positivity, but not on IA-2A, suggests differences in biology. These data provide a context for clinicians to interpret results of autoantibody testing in clinical practice.