The first epidemiological study of presymptomatic type 1 diabetes among first-degree relatives in Japan: PREP-T1D study

AIMS: To identify individuals with a disease process comparable to presymptomatic stages of type 1 diabetes (T1D) and to evaluate their prevalence among first-degree relatives in Japan. METHODS: In this nationwide multicenter observational study conducted at 71 sites, 2,614 first-degree relatives of individuals with T1D underwent islet autoantibody (IAb) screening. Participants positive for ≥1 IAb received metabolic evaluation, including oral glucose tolerance testing, to classify presymptomatic stage. RESULTS: IAb positivity was identified in 95 participants (3.6%), including 16 (0.6%) with multiple-IAb positivity, with ZnT8A (49.5%, 47 of 95) and GADA (42.1%, 40) being the most frequent. 5 participants met stage 1 criteria, 9 were classified as stage 2, and 2 as stage 3. The most common HLA-A allele was A*24:02 (36.8%), with the predominant DRB1-DQB1 haplotypes being *09:01-*03:03 (24.2%) and *04:05-*04:01 (23.6%). CONCLUSIONS: From this first study describing the epidemiological characteristics of presymptomatic T1D in Japan and Asia, it was shown that the prevalence of IAbs in Japan was comparable to that in other countries, underscoring the importance of screening and monitoring for presymptomatic T1D in Japan as well. Further studies involving longitudinal observation of IAb-positive individuals are crucial for establishing an effective screening and monitoring system.