A Longitudinal Study of GAD65 and ICA512 Autoantibodies During the Progression to Type 1 Diabetes in Diabetes Prevention Trial–Type 1 (DPT-1) Participants

OBJECTIVE: We examined changes in GAD65 and ICA-512 autoantibodies (GADA and IA-2A) during progression to type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Diabetes Prevention Trial–Type 1 (DPT-1) participants were assessed for changes in positivity and titers of GADA and IA-2A during the progression to T1D. RESULTS: Among 99 progressors to T1D with GADA and IA-2A measurements at baseline and diagnosis (mean interval = 3.3 ± 1.5 years), GADA positivity changed little and GADA titers decreased (P < 0.01). In contrast, both IA-2A positivity and titers increased substantially (P < 0.001). Even among those positive at baseline, IA-2A titers increased from baseline to diagnosis (n = 57; P < 0.001), whereas GADA titers decreased (n = 80; P < 0.01). The same patterns of change were also evident among those positive for both autoantibodies (n = 48) at baseline. CONCLUSIONS: IA-2A titers increase during the years before the diagnosis of T1D, even among those positive for IA-2A. In contrast, GADA titers tend to decline during those years.