1150-P: Improving Early Diagnosis of Presymptomatic Stage 2 Type 1 Diabetes with a Sample-Sparing Assay

Abstract

Teplizumab was approved by the FDA in Nov 2022 as the first therapeutic to delay progression of type 1 diabetes from pre-symptomatic stage 2 to clinical onset stage 3. Nevertheless, individuals with stage 2 type 1 diabetes do not exist in hospital systems, and more than 85% of them do not have family history. Large scale population testing remains the only effective way of identifying eligible patients for disease interventional drugs. Thus, accurate, accessible and low cost tests are urgently needed to implement such screening programs. To that end, we have conducted a pilot retrospective screening efficacy study with blinded serum specimens from the Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) study from the NIDDK central repository. A total of 97 serum specimen from subjects that either developed T1D within 5 years (i.e. 50 progressors) or had at least 5 years of follow-up (i.e. 47 progressors) were included in the study. A subject was considered high-risk for T1D progression if positive for two or more islet autoantibodies, and vice versa. Under this scheme, the multiplex ADAP assay achieved PPV and NPV of 49% and 92% for 5 years progression risks. The matching radiobinding assay (RBA) had PPV and NPV of 50% and 77% in this cohort. The improved NPV stemmed from 12 progressors tested positive for multiple islet autoantibodies by multiplex ADAP but not by RBA. Notably, 6 out of these 12 subjects tested positive for multiple islet autoantibodies by RBA in subsequent sampling events with a median delay of 2.8 years compared to multiplex ADAP. In summary, the multiplex ADAP assay could be an ideal tool for large scale identification of individuals with stage 2 type 1 diabetes due to its sample-sparing nature (i.e. 4µL serum input), non-radioactiveness, compatibility with widely-available real-time qPCR instruments and favorable risk prediction capability. Disclosure J. Tsai: Stock/Shareholder; Enable Biosciences. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R44DK124009-01)