1377-P: Phenotypic Heterogeneity and Risk for Type 2 Diabetes in Central European and South Asian People with Prediabetes

Introduction and Objective: Prediabetes is a high-risk state for the development of type 2 diabetes (T2D), with large heterogeneity for the risk of progression and complications and additional variation imposed by ethnicity. This study aimed to develop an unified data-driven approach to characterize individuals with prediabetes and assess differences in risk profiles of European and South Asian (Indian) populations. Methods: Data from Central Europeans (n = 1628) and South Asians (n = 5171), who underwent a 75 g oral glucose tolerance test, were analyzed. Prediabetes was defined by ADA criteria. We selected nine common clinical traits in each cohort. Partitioning around medoids algorithm was employed and cluster number was determined by evaluating Jaccard stability. We determined risk for adverse events by calculating Hazard ratios (HR) corrected for age and sex. Results: The Asian Indian cohort was younger (48.4 years ± 10.9 vs 52.2 ± 13.5, p < 0.01) and had a lower body mass index (27.8 kg/m2 ± 4.5 vs 32.9 ± 8.9, p < 0.01), however had higher HbA1c, fasting and post-challenge glucose. Consensus clustering yielded 5 stable clusters: Young/Overweight, Isolated IFG, Age-related, High Glycemia and Obesity-related. The High Glycemia Cluster had the highest risk to develop T2D and also Age-related and Obesity-related Clusters had increased T2D risk in both cohorts. However, the Young/Overweight Cluster had elevated T2D risk only in the Asian Indian Cohort. On the contrary, future nephropathy risk was elevated in the Age-related and High Glycemia Clusters among Central Europeans but not South Asians. Conclusion: This study establishes an overarching sub-phenotyping framework for individuals with prediabetes and its complications, revealing ethnic differences and commonalities in risk profiles. This approach facilitates the unprecedented undertaking to compare disease trajectories and, in future, treatment responses in individuals from diverse ethnic communities. Disclosure V. Baskar: None. M. Ganslmeier: None. A. Vignesh: None. J. S: None. H. Preissl: None. R. Wagner: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. A. Peter: None. R. Lehmann: None. N. Perakakis: Other Relationship; Novo Nordisk, Lilly Diabetes. Advisory Panel; Bayer Pharmaceuticals, Inc. Other Relationship; APOGEPHA, Transmedac Innovations AG, GWT-TUD, Elbe-Gesundsheintszentrum GmbH, Open Exploration. K. Mai: None. S. Kabisch: Research Support; Almond Board California, California Walnut Commission. Other Relationship; JuZo-Akademie, Boehringer-Ingelheim. Research Support; J. Rettenmaier & Söhne. Other Relationship; Lilly Diabetes. Research Support; Wilhelm-Doerenkamp-Foundation. M. Blüher: Advisory Panel; AstraZeneca. Speaker's Bureau; Amgen Inc. Advisory Panel; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Eli Lilly and Company, Novo Nordisk, Nestlé Health Science, Sanofi-Aventis Deutschland GmbH. P.E. Schwarz: None. J. Seissler: None. I. Yurchenko: None. M. Heni: Advisory Panel; Amryt Pharma. Speaker's Bureau; Amryt Pharma, AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. J. Szendroedi: Advisory Panel; Novo Nordisk, Lilly Diabetes, Novartis AG, Boehringer-Ingelheim. A. Schürmann: None. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker's Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Consultant; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Consultant; Pfizer Inc. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Novo Nordisk, GlaxoSmithKline plc. Consultant; GlaxoSmithKline plc. A. Fritsche: Advisory Panel; Abbott. Speaker's Bureau; AstraZeneca. A. Daniel: None. R. Anjana: None. A.L. Birkenfeld: None. V. Mohan: Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Servier Laboratories. Speaker's Bureau; USV Private Limited, Sanofi, Medtronic, Eli Lilly and Company. R. Jumpertz von Schwartzenberg: None. Funding German Center for Diabetes Research (DZD)