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

  1. George Eisenbarth, MD, PHD5
  1. 1Division of Endocrinology, University of Miami, Miami, Florida
  2. 2Division of Endocrinology, Metabolism, and Nutrition, VA Puget Sound Health Care System, University of Washington, Seattle, Washington
  3. 3Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida
  4. 4Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida
  5. 5HLA/DNA Laboratory, Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, Colorado
  6. 6Division of Endocrinology, University of Florida, Gainesville, Florida
  7. 7Joslin Diabetes Center, Boston, Massachusetts
  1. Corresponding author: Jay M. Sosenko, jsosenko{at}


OBJECTIVE We examined changes in GAD65 and islet cell autoantibody-512 autoantibodies (GADA and IA-2 antigen [IA-2A]) during progression to type 1 diabetes (T1D).

RESEARCH DESIGN AND METHODS Diabetes Prevention Trial–Type 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.

  • Received May 25, 2011.
  • Accepted August 2, 2011.

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