Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1.

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.

• Authors: Tihamer Orban, Jay M Sosenko, David Cuthbertson, Jeffrey P Krischer, Jay S Skyler, Richard Jackson, Liping Yu, Jerry P Palmer, Desmond Schatz, George Eisenbarth, Diabetes Prevention Trial-Type 1 Study Group
• Journal: Diabetes care (Diabetes Care) Vol. 32 Issue 12 Pg. 2269-74 (Dec 2009) ISSN: 1935-5548 [Electronic] United States
• PMID: 19741189 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Receptor-Like Protein Tyrosine Phosphatases, Class 8
• Glutamate Decarboxylase
• glutamate decarboxylase 2

Topics

• Autoantibodies (analysis)
• Cohort Studies
• Diabetes Mellitus, Type 1 (diagnosis, enzymology, immunology, prevention & control)
• Glutamate Decarboxylase (immunology)
• Humans
• Islets of Langerhans (immunology)
• Predictive Value of Tests
• Prospective Studies
• Receptor-Like Protein Tyrosine Phosphatases, Class 8 (immunology)
• Surveys and Questionnaires