1292-P: Loss of Multiple Islet Autoantibody Status during Progression to Type 1 Diabetes

Introduction & Objective: Type 1 diabetes (T1D) can be diagnosed before clinical symptoms with the presence of multiple islet autoantibodies (IA) and normoglycemia - stage 1 or IA and dysglycemia - stage 2. Early-stage diagnosis allows for treatment with FDA approved teplizumab or agents being tested in clinical trials. Both options require the presence of two or more IA for eligibility; however, some individuals lose IA prior to clinical diagnosis. We explored the frequency and predictors of regression from multiple to single or negative IA status in youth who progressed to clinical T1D.

Methods: Youth with at least two IA evaluation visits prior to clinical T1D onset were included. They participated in Diabetes Autoimmunity Study in the Young (DAISY) cohort (n=90, median 14 visits/person) or Autoimmunity Screening for Kids (ASK) screening study (n=61, median 4 visits/person).

Results: Of those who progressed to clinical T1D, 92% in DAISY and 84% in ASK were multiple IA+ at least once. However, many multiple IA youth, 39% (32/83) in DAISY and 10% (5/51) in ASK, regressed to single or negative IA status prior to clinical diagnosis. The mean time from multiple to single or negative IA status was 4.0 (2.3-143.3) months. IA regression was more common in males (p=0.025), controlling for the effect of study (ASK vs DAISY). Among youth seen while in stage 2, 30% (32/106) had single or negative IA status. 54% (17/32) of progressors with single or negative IA status in stage 2 T1D had previously been multiple IA+.

Conclusions: IA levels fluctuate over time. With cross-sectional screening for T1D, many patients testing positive for a single IA may have had multiple IA historically. Current eligibility criteria for teplizumab treatment or participation in clinical trials appear too restrictive and may exclude youth who will progress to clinical T1D despite absence of multiple IA.