MON-237 Prevalence, diagnostic utility, and clinical characteristics of ZnT8 antibody in children and adolescent with diabetes mellitus in South Korea

Abstract Disclosure: H. Woo: None. S. Shin: None. H. Lee: None. Y. Lee: None. H. Kim: None. Y. Lee: None. C. Shin: None. H. Lee: None. J. Kim: None. Background: Zinc transporter 8 (ZnT8) is a transmembrane protein that transports zinc into insulin vesicles. Autoantibodies to ZnT8 (ZnT8A) serve as valuable markers for the diagnosis, prediction, and differentiation of clinical phenotypes of type 1 diabetes mellitus (T1DM). We investigated the prevalence, diagnostic utility, and clinical characteristics of ZnT8A in children and adolescents with diabetes mellitus in South Korea. Methods: ZnT8A levels were measured in childhood-onset (<19 years) DM patients diagnosed within three years between 2019 and 2024 at two tertiary hospitals (n=275). ZnT8A levels were also measured in healthy controls (19-29 years, n=100). The cut-off for ZnT8A positivity was set at ≥15 U/ml according to the manufacturer's recommendations. We compared clinical characteristics between ZnT8A-positive and ZnT8A-negative patients within each diabetes subtype. Results: There were 160 patients (60.4%) with T1DM and 105 (39.6%) with type 2 diabetes mellitus (T2DM). The mean age at diagnosis for all patients was 11.4 years, and the proportion of males was 49.1%. At the time of diagnosis, clinical characteristics such as age, sex, BMI, SDS, HbA1c, serum insulin, C-peptide, 24-hour urine C-peptide, and lipid profile (HDL and TG) showed significant differences between patients with T1DM and T2DM (all P<0.005). In patients with T1DM, T2DM, and healthy controls, the positivity rate for at least one diabetes-associated autoantibody (DAA) was 94.4%, 8.6%, and 11%, respectively. The prevalence of specific DAA in T1DM, T2DM, and healthy controls was as follows: ZnT8A, 76.3%, 0%, and 0%; islet antigen-2 antibody (IA2A), 74.3%, 0%, and 5%; glutamate decarboxylase antibody (GADA), 60.6%, 1.9%, and 0%; and insulin autoantibody (IAA), 31.9%, 6.7%, and 6%. In T1DM patients, the positivity rates for a single antibody were ZnT8A, 3.1%; IA2A, 4.4%; GADA, 4.4%; IAA, 1.2%. In T1DM patients, ZnT8A positivity was associated with younger age (9.2±3.8 years vs. 10.7±4.8 years), higher proportion of prepubertal children (54.6% vs. 36.8%), more males (45.1% vs. 26.3%), and lower Hashimoto's thyroiditis diagnosis rate (11.5% vs. 31.6%) (all P<0.005). Conclusions: ZnT8A is highly prevalent in South Korean children and adolescents with T1DM, especially in younger patients. Further studies are needed to investigate the clinical characteristics and course of diabetes in patients who are positive for ZnT8A. Presentation: Monday, July 14, 2025