T2D is a heterogeneous disease. Individuals in the Swedish All New Diabetics in Scania (ANDIS) cohort with newly diagnosed T2D were grouped by 6 demographic and clinical variables to show 4 distinct T2D subtypes with differential risk for nephropathy and retinopathy. We tested the predictive validity of this clustering system for patients with advanced T2D in DEVOTE (a large, global, randomized, double-blind, cardiovascular outcomes trial; median observation time: 1.99 years) for major adverse cardiovascular event (MACE)-free survival, severe hypoglycemia (SH)-free survival, and overall survival rates. Subjects (N=7637, mean age=65.0 years, mean T2D duration=16.4 years, mean glycated hemoglobin [A1C]=8.43%) were assigned to a cluster for which they had the smallest Euclidean distance to the cluster center based on available baseline variables: A1C, BMI, age, age at diagnosis. Insulin resistance and sensitivity measures were not available. The 4 DEVOTE clusters showed baseline characteristics consistent with the original ANDIS clusters, with significant differences in MACE-incidence and SH-incidence (Table). The results were confirmed using data from the LEADER trial (data not shown). The study suggests that clusters derived from early T2D can be replicated in long-standing T2D. Future work should characterize differences in treatment response across clusters to improve outcomes across the heterogeneous T2D population.
A.R. Kahkoska: None. E. Hachmann-Nielsen: Employee; Self; Novo Nordisk A/S. K. Klein: None. K.G. Kongsbak: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. K. Kvist: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc.