Type 2 diabetes (T2D) is a heterogeneous metabolic disease that captures individuals with hyperglycemia who do not meet criteria for other forms of diabetes (e.g., type 1 diabetes or monogenic diabetes). Consequently, T2D is a diagnosis of exclusion and current criteria do not reflect the multiple etiologic pathways by which hyperglycemia can transpire. To better understand and characterize heterogeneity in T2D, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) funded the DEFINE-T2D consortium in 2024 to identify clinically relevant subtypes of T2D. The consortium comprises a Biostatistics Research Center to coordinate data analysis plus day-to-day operations and four study sites that bring data from 13 observational cohorts, four randomized controlled trials, and six electronic health records/biobanks. Together, these sources contribute a sample size of >4.8 million individuals – primarily adults – many of whom have prediabetes or T2D. In the upcoming four years, DEFINE-T2D will leverage multiple types of data including clinical information, genetics, multi-omics (e.g., proteomics, metabolomics), environmental exposures, lifestyle behaviors, and social determinants of health to identify discrete subtypes of T2D. The consortium will identify functional biomarkers of subtypes and determine if subtypes show differential associations with complications and comorbidities. Findings from the DEFINE-T2D consortium will contribute to current understanding of T2D pathophysiology and inform prediction models of T2D onset and progression across the spectrum of disease. Ultimately, this work is expected to provide tools that will inform clinical practices surrounding the prevention, diagnosis, and management of T2D, and improve quality of life for those affected by this increasingly common metabolic disease.
