MON-229 Exploring the Heterogeneity of Type 1 Diabetes: A Continuum from Typical to Atypical Presentations and Monogenic Diabetes

Abstract Disclosure: A. Harvengt: None. P. Lysy: None. Background: Type 1 diabetes (T1D) is a heterogeneous disease with varying clinical presentations. Recent advancements in diabetes sub-classification have improved the differentiation between T1D and type 2 diabetes, but the overlap with monogenic diabetes remains poorly understood. Our team developed the DIAMODIA criteria to screen for monogenic diabetes in patients with atypical diabetes presentations. Objective: To evaluate the clinical and glycemic characteristics of patients with atypical diabetes identified by DIAMODIA criteria and to explore the continuum between typical T1D, atypical diabetes, and monogenic diabetes. Methods: We analyzed a cohort of 424 pediatric patients with diabetes, including 337 with typical T1D (Tdia cohort), 53 with atypical diabetes (Adia cohort) identified by DIAMODIA criteria, and 34 with confirmed monogenic diabetes (MODY cohort). Clinical and glycemic parameters were compared across these groups. Genetic analysis, including MODY panel and whole exome sequencing (WES), was performed on the Adia cohort to identify potential monogenic variants. Results: The Adia cohort exhibited intermediate clinical and glycemic characteristics between the Tdia and MODY cohorts. Key findings included lower glycemic levels at diagnosis in the Adia cohort compared to Tdia (478.95 ± 215.16 mg/dL vs. 405.28 ± 209.9 mg/dL, p=0.02) but higher than in MODY (203.38 ± 194.7 mg/dL, p<0.001). Long-term glycemic control was better in MODY than in Adia, and in Adia than in Tdia, as evidenced by HbA1c levels (MODY: 7.14 ± 2.2%, Adia: 10.88 ± 2.4%, Tdia: 11.47 ± 2.2%, p<0.001). Glycemic variability, assessed by IDAA1c and GTAA1c scores, was significantly lower in MODY (IDAA1c: 7.09 ± 1.9, GTAA1c: 3.79 ± 1.3) compared to Adia (IDAA1c: 9.71 ± 1.4, GTAA1c: 4.97 ± 0.8) and Tdia (IDAA1c: 11.34 ± 1.4, GTAA1c: 6.25 ± 1.0, p<0.001). Time in range (TIR70-180) was significantly higher in MODY (76.94 ± 17.19%) than in Adia (52.20 ± 9.73%) and Tdia (43.37 ± 8.73%, p<0.001). Conclusion: Our findings highlight the clinical heterogeneity of diabetes, with a continuum of presentations from typical T1D to monogenic diabetes, bridged by atypical diabetes. Despite the DIAMODIA criteria effectively distinguishing between T1D and MODY, no monogenic variants were confirmed in the Adia cohort, suggesting the presence of yet unidentified genetic or environmental factors. This study underscores the complexity of diabetes classification and the need for further research to elucidate the underlying mechanisms of atypical diabetes. Presentation: Monday, July 14, 2025