Pancreatic Islet Autoantibodies as Predictors of Type 1 Diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1)

  1. Tihamer Orban, MD(1),
  2. Jay M. Sosenko, MD (jsosenko{at}med.miami.edu)(2),
  3. David Cuthbertson, MS(3),
  4. Jeffrey P. Krischer, PhD(4),
  5. Jay S. Skyler, MD(2),
  6. Richard Jackson(1),
  7. Liping Yu, MD(5),
  8. Jerry P. Palmer, MD(6),
  9. Desmond Schatz, MD(7),
  10. George Eisenbarth, MD, PhD(5) and
  11. Diabetes Prevention Trial-1Study Group(1)
  1. (1) Joslin Diabetes Center, Boston, Massachusetts
  2. (2) Division of Endocrinology, University of Miami, Miami, FL
  3. (3) Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida
  4. (4) Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida
  5. (5) Barbara Davis Center for Childhood Diabetes, Denver, Colorado
  6. (6) Division of Endocrinology/Metabolism, University of Washington, Seattle, Washington
  7. (7) Division of Endocrinology, University of Florida, Gainesville, FL

    Abstract

    Objective. There is limited information from large-scale prospective studies regarding the prediction of type 1 diabetes (T1D) by specific types of pancreatic islet autoantibodies, either alone or in combination. Thus, we studied the extent to which specific autoantibodies are predictive of T1D.

    Research Design and Methods. Two cohorts were derived from the first screening for islet cell autoantibodies (ICA) in the Diabetes Prevention Trial-1 (DPT-1). Autoantibodies to glutamic acid decarboxylase 65 (GAD65), insulinoma associated antigen-2 (ICA512), and insulin (micro IAA or mIAA) were also measured. Participants were followed for the occurrence of T1D. One cohort (Questionnaire) included those who did not enter the DPT-1 trials, but responded to questionnaires (n=28,507, 2.4% ICA positive). The other cohort (Trials) included DPT-1 trial participants (n=528, 83.3% ICA positive).

    Results. In both cohorts autoantibody number was highly predictive of T1D (p<0.001). The Questionnaire cohort was utilized to assess prediction according to the type of autoantibody. As single autoantibodies, ICA (3.9%), GAD65 (4.4%) and ICA512 (4.6%) were similarly predictive of T1D in proportional hazards models (p<0.001 for all). However, none with mIAA as single autoantibodies developed T1D. As second autoantibodies, all except mIAA added significantly (p<0.001) to the prediction of T1D. Within the positive range, GAD65 and ICA autoantibody titers were predictive of T1D.

    Conclusions. The data indicate that the number of autoantibodies is predictive of T1D. However, mIAA is less predictive of T1D than other autoantibodies. Autoantibody number, type of autoantibody and autoantibody titer must be carefully considered in planning prevention trials for T1D.

    Footnotes

      • Received May 21, 2009.
      • Accepted August 31, 2009.

    This Article

    1. Diabetes Care
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