Pancreatic Islet Autoantibodies as Predictors of Type 1 Diabetes in the Diabetes Prevention Trial–Type 1

  1. Tihamer Orban, MD1,
  2. Jay M. Sosenko, MD2,
  3. David Cuthbertson, MS3,
  4. Jeffrey P. Krischer, PHD4,
  5. Jay S. Skyler, MD2,
  6. Richard Jackson, MD1,
  7. Liping Yu, MD5,
  8. Jerry P. Palmer, MD6,
  9. Desmond Schatz, MD7,
  10. George Eisenbarth, MD, PHD5 and
  11. for the Diabetes Prevention Trial–Type 1 Study Group
  1. 1Joslin Diabetes Center, Boston, Massachusetts;
  2. 2Division of Endocrinology, University of Miami, Miami, Florida;
  3. 3Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida;
  4. 4Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida;
  5. 5Barbara Davis Center for Childhood Diabetes, Denver, Colorado;
  6. 6Division of Endocrinology/Metabolism, University of Washington, Seattle, Washington;
  7. 7Division of Endocrinology, University of Florida, Gainesville, Florida.
  1. Corresponding author: Jay M. Sosenko, jsosenko{at}med.miami.edu.

Abstract

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

RESEARCH DESIGN AND METHODS Two cohorts were derived from the first screening for islet cell autoantibodies (ICAs) in the Diabetes Prevention Trial–Type 1 (DPT-1). Autoantibodies to GAD 65 (GAD65), insulinoma-associated antigen-2 (ICA512), and insulin (micro-IAA [mIAA]) were also measured. Participants were followed for the occurrence of type 1 diabetes. One cohort (Questionnaire) included those who did not enter the DPT-1 trials, but responded to questionnaires (n = 28,507, 2.4% ICA+). The other cohort (Trials) included DPT-1 participants (n = 528, 83.3% ICA+).

RESULTS In both cohorts autoantibody number was highly predictive of type 1 diabetes (P < 0.001). The Questionnaire cohort was used 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 type 1 diabetes in proportional hazards models (P < 0.001 for all). However, no subjects with mIAA as single autoantibodies developed type 1 diabetes. As second autoantibodies, all except mIAA added significantly (P < 0.001) to the prediction of type 1 diabetes. Within the positive range, GAD65 and ICA autoantibody titers were predictive of type 1 diabetes.

CONCLUSIONS The data indicate that the number of autoantibodies is predictive of type 1 diabetes. However, mIAA is less predictive of type 1 diabetes than other autoantibodies. Autoantibody number, type of autoantibody, and autoantibody titer must be carefully considered in planning prevention trials for type 1 diabetes.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received May 21, 2009.
    • Accepted August 31, 2009.
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  1. Diabetes Care vol. 32 no. 12 2269-2274
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