Identification of Different Age-at-Diagnosis-Based Endotypes and Clinical Phenotypes in a Cohort of Adult Patients Diagnosed with Type 1 Diabetes

Background/Objectives: Type 1 diabetes (T1D) is a heterogeneous disease in terms of clinical presentation, treatment requirements, and risk of complications. The identification of biological endotypes and clinical phenotypes has been proposed to support precision medicine approaches. We aimed to assess the prevalence and clinical characteristics of age-at-diagnosis-based endotypes, adult-onset phenotypes, and insulin-resistant phenotypes in a real-world cohort of adults with T1D. Methods: We conducted a single-center, observational, cross-sectional study including adults (≥18 years) with clinically confirmed T1D under active follow-up. Clinical, metabolic, and treatment-related variables were analyzed across predefined age-at-diagnosis-based endotypes and clinical phenotypes. Results: A total of 868 patients were included (median age 49 years; diabetes duration 23 years; age at diagnosis 20 years; 51.5% women). Continuous subcutaneous insulin infusion (CSII) was used by 20.4% of patients, and continuous glucose monitoring (CGM) was used by 95.3%. Mean HbA1c was 7.47%, with a median time in range (TIR) of 63%. The prevalence of age-at-diagnosis-based endotype 1 (ED1) was 11.8%, adult-onset phenotype was 31.3%, and insulin-resistant phenotype was 7.3%. No major differences in glycemic control were observed across age-at-diagnosis-based endotypes. Associations between endotypes and treatment-related variables were largely explained by current age and diabetes duration. In contrast, the adult-onset phenotype was independently associated with lower TIR, higher time above range, lower use of CSII, and greater use of adjunctive therapies. The insulin-resistant phenotype was associated with higher HbA1c, lower TIR, and greater therapeutic complexity. Conclusions: Adult T1D shows marked heterogeneity. In this real-world cohort, age-at-diagnosis-based endotypes were not independently associated with major clinical differences after adjustment for current age and diabetes duration. In contrast, adult-onset and insulin-resistant phenotypes identified subgroups with poorer glycemic control and greater therapeutic complexity.