2243-P: Precision Subtyping of Adult-Onset Autoimmune Diabetes: Clinical Feature-Driven Approaches

Introduction and Objective: Adult-onset autoimmune (AOA) diabetes encompassed a broad clinical spectrum that is categorized into classic type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, this broad classification failed to capture the marked heterogeneity in β-cell function, autoimmunity, and treatment needs. This study aimed to develop a more granular classification system for AOA diabetes to facilitate precise diagnosis and treatment. Methods: We retrospectively enrolled patients with AOA diabetes between 2010-2024. Patients were divided into classic T1D and LADA based on conventional category. K-means cluster analysis was conducted separately in classic T1D and LADA based on clinical variables including age at onset, DKA at onset, fasting C-peptide level and the number of islet autoantibodies (IAbs). Results: Among 884 patients with AOA diabetes, 708 were divided into classic T1D and 176 into LADA. Cluster analysis stratified AOA diabetes into six distinct subtypes: three within the classic T1D spectrum (T1D-C1, C2, C3) and three within the LADA spectrum (LADA-C1, C2, C3). Intergroup comparisons revealed that the LADA-C1 subtype had a lower age of onset and fasting C-peptide levels compared to LADA-C2 and C3, along with lower IAbs positivity and DKA incidence, exhibiting characteristics of classic T1D. In contrast, the classic T1D-C3 subtype had a moderate age of onset, the highest fasting C-peptide levels, and the lowest DKA incidence, displaying clinical features of LADA. Comparative analysis of these two confounding subtypes revealed significant differences in their disease progression and therapeutic requirements. Patients with classic T1D-C3 exhibited a more rapid rate of C-peptide decline. Furthermore, the LADA-C1 subgroup responded favorably to oral hypoglycemic agents for a longer duration. Conclusion: A simple clinical feature-driven clustering approach can refine the classification of AOA diabetes into six reproducible subtypes with distinct patterns of β-cell failure and treatment needs. Disclosure M. Zhang: None. M. Huang: None.