The presence of multiple islet autoantibodies (Ab) and higher Ab levels increase risk of type 1 diabetes (T1D); however, the predictive value of remitting Ab positivity is unknown. The Environmental Determinants of Diabetes in the Young (TEDDY) Study evaluated the frequency of Ab remission and how it affects risk of T1D. Genetically high-risk children (n=8502) were screened for mIAA, GADA, and IA-2A every 3 months, between 0.25-8 years of age. Persistent Ab positivity was defined as a positive Ab test on two consecutive visits and confirmed in two laboratories. Remission was defined as reversion from persistent positive to negative.
Of the 512 children who developed a persistent positive Ab, 375 had mIAA, 375 GADA, and 214 IA-2A. A large proportion of the Abs remitted during the follow-up: 39% mIAA, 21% GADA and 5% IA-2A. The median (interquartile range) months to remission was 12 (6-21) for mIAA, 6 (9-18) for GADA and 9 (6-12) for IA-2A. As expected, baseline Ab level predicted remission; 1 SD increase in baseline level reduced remission by 19% for mIAA, 55% for GADA, and 65% for IA2A. Gender, family history of T1D, HLA-DR,DQ, and age at seroconversion did not predict remission for any of the Abs. MIAA level was the strongest predictor of T1D risk (HR 1.06, 95%CI 1.04 – 1.07, p<0.0001), controlling for age at seroconversion, other Abs, and subject characteristics. Interestingly, GADA remission, not level, predicted T1D (HR 2.02, 95%CI 1.02 – 3.99, p=0.04), controlling for the same factors and GADA titer. IA-2A remission or level was not associated with T1D.
The predictive value of autoantibody levels and remission appears to vary by Ab.Funded by NIH, NIDDK, NIAID, NICHD, NIEHS, JDRF and CDC.