Integration of clinical and proteomic risk factors enhances prognostic modelling of incident vascular complications in type 2 diabetes
Authors' conclusion
Integrating proteomics with clinical data enhances risk prediction of type 2 diabetes vascular complications, especially for macrovascular outcomes.
Study context
- Population
- European-ancestry UK Biobank participants with prevalent T2D but no prior vascular disease at baseline; 2,923 plasma proteins analysedEuropean ancestry
- Participants
- 917 participants
- Comparison
- Proteomics-integrated models vs clinical-only models
- Outcome
- Time to first macrovascular or microvascular complication (ICD-10 codes)
- Follow-up
- Mean 10.41 years
Methodological detailscohort, UK Biobank, clinical-variables-prioritized LASSO Cox regression across 100 resamples, optimism-corrected C-index, time-dependent AUC and Brier score, exploratory cross-ancestry generalizability analyses
- Cohort, UK Biobank
- Clinical-variables-prioritized LASSO Cox regression across 100 resamples
- Optimism-corrected C-index, time-dependent AUC and Brier score
- Exploratory cross-ancestry generalizability analyses
Performance
As reported in the abstract
Prediction of T2D vascular complications (Harrell's C)
Harrell's C, macrovascular: proteomics-integrated vs clinical-only
0.72 vs. 0.60
Harrell's C, microvascular: proteomics-integrated vs clinical-only
0.67 vs. 0.62
Proteins selected for macrovascular outcomes (led by LRRC37A2, NT-proBNP, CHGA, APOD and STAB2)
37
Proteins selected for microvascular complications (led by IL15, FAM3C and TNFSF11), more moderate stability
9
Further findings
Stability of prognostic accuracy over time · 10 years
- Stable prognostic accuracy over 10 years for macrovascular outcomes
Cross-ancestry generalizability
- Predictive gains maintained in European genetic outliers (n=116) but diminished in African (n=54) and Asian (n=80) participants
- Exploratory
Original publication
Integration of clinical and proteomic risk factors enhances prognostic modelling of incident vascular complications in type 2 diabetes. Cardiovasc Diabetol. Published 20 January 2026. doi:10.
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