Testing IA2beta Autoantibodies (aab) with other Islet aab Improves Type 1 Diabetes (T1D) Prediction
Abstract Number: 1005-P
Authors: HUI PENG, EMILY WION, MARTHA PYNE, MICHAEL BRANTLEY, LILY CONSTANS, MELISSA JACKSON, ADAM JENSEN, WILLIAM HAGOPIAN, Seattle, WA
Institutions: Seattle, WA
Results: Two long-term prospective T1D prediction studies, the Washington State Diabetes Prediction Study (WSDPS) and the more recent Diabetes Evaluation in Washington Study (DEW-IT), were used to test the predictive value of multiple "defined" islet aab (MAab) (2 or more aab to GAD65, IA2 and insulin) alone and together with aab to IA2beta. Children seropositive for MAab were followed prospectively to T1D. Aab were detected by established radiobinding assays using protein A bound to microtiter plates.
In the WSDPS study, 12 children had MAab by age 14. Of these, 7 had IA2beta aab. After 16 years of follow-up, 8 of 12 MAab subjects developed T1D (67% positive predictive value (PPV), 95% CI 35-89%), while 6 of 7 subjects with IA2beta aab developed T1D (86% PPV, 95% CI 42-99%). Six of 8 subjects with T1D (75% of cases, 95% CI 52-100%) had IA-2beta aab. Survival analysis compared disease outcome for MAab subjects with IA2beta aab versus those without IA2beta aab. IA2beta aab significantly marked progression to T1D within 16 years (p=0.041).
In the DEW-IT study, 29 children developed MAab by age 9, and 15 of these also had IA2-beta aab. After 3 years of follow-up, 6 of the 29 children developed T1D. Five of these 6 subjects also had IA2beta aab. In this shorter follow-up, MAab had 21% PPV (95% CI 9-40%). In the MAab positive subjects, IA2beta aab had 33% PPV (95% CI 13-61%) and included 83% of cases (95% CI 37-99%). However, in this short follow-up, the added presence of IA2beta aab did not mark significantly increased probability to develop T1D (p=0.19). Prospective follow-up of this cohort continues.
We conclude that in long-term prospective follow-up, MAab successfully identified children who would develop T1D. The additional presence of IA2beta aab significantly increased PPV if the prospective follow-up period was sufficiently long. Testing for IA2beta aab along with the more established islet aab tests might be especially useful for pre-diabetes intervention studies requiring high PPV.[figure1]