Introduction and Objective: People with diabetes frequently develop cardiovascular (CV) disease and cancer, but the shared biological pathways are unclear. We compared their proteomic signatures. Methods: We analyzed 3,215 UK Biobank participants with diabetes and plasma proteomics, classified as no complications, cancer only, CV disease only, or both. Protein expression was FDR-adjusted versus no complications. Results: Upregulated proteins included NT-proBNP, HAVCR1, GDF15, and IGFBP2, reflecting hemodynamic stress, kidney injury, inflammation, and metabolic signaling. Downregulated proteins (S100A4, DCXR, SDC4, TCL1A) suggested reduced matrix integrity and metabolic resilience. Effects were strongest in the combined CV and cancer group. Conclusion: CV disease and cancer in diabetes share key proteomic pathways, supporting a systems-based multimorbidity model. Disclosure J. Calvo-Marin: Speaker's Bureau; Current; Novo Nordisk, AstraZeneca, Abbott Diabetes, Roche Diabetes Care. F. Ruiz Salazar: Speaker's Bureau; Current; Abbott Diagnostics, AstraZeneca, Novo Nordisk A/S. Advisory Panel; Current; Roche Diagnostics. V. Mora-Gomez: None. M. Lutz: None. G. Torrealba-Acosta: None.
Calvo-Marín et al. (2026) studied this question.