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


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.
Orban
Tihamer
T
Joslin Diabetes Center, Boston, Massachusetts, USA.
Sosenko
Jay M
JM
Cuthbertson
David
D
Krischer
Jeffrey P
JP
Skyler
Jay S
JS
Jackson
Richard
R
Yu
Liping
L
Palmer
Jerry P
JP
Schatz
Desmond
D
Eisenbarth
George
G
D001323:Autoantibodies / Q000032:analysis*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D011795:Surveys and Questionnaires
D001323:Autoantibodies; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2