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

作者：Tihamer Orban, Jay M. Sosenko, David Cuthbertson, Jeffrey P. Krischer, Jay S. Skyler, Richard A. Jackson, Liping Yu, Jerry P. Palmer, Desmond Schatz, George S. Eisenbarth, for the Diabetes Prevention Trial–Type 1 Study Group · 发表于：Diabetes Care · 年份：2009 · DOI：10.2337/dc09-0934 · 被引用次数：259 · 研究领域：Diabetes and associated disorders、Pancreatic function and diabetes、Diabetes Management and Research

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 pr...