PT  - JOURNAL ARTICLE
AU  - Orban, Tihamer
AU  - Sosenko, Jay M.
AU  - Cuthbertson, David
AU  - Krischer, Jeffrey P.
AU  - Skyler, Jay S.
AU  - Jackson, Richard
AU  - Yu, Liping
AU  - Palmer, Jerry P.
AU  - Schatz, Desmond
AU  - Eisenbarth, George
AU  - , 
TI  - Pancreatic Islet Autoantibodies as Predictors of Type 1 Diabetes in the Diabetes Prevention Trial–Type 1
AID  - 10.2337/dc09-0934
DP  - 2009 Dec 01
TA  - Diabetes Care
PG  - 2269--2274
VI  - 32
IP  - 12
4099  - http://care.diabetesjournals.org/content/32/12/2269.short
4100  - http://care.diabetesjournals.org/content/32/12/2269.full
SO  - Diabetes Care2009 Dec 01; 32
AB  - 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. © 2009 by the American Diabetes Association.