Large‐Scale Plasma Proteomics Enhances Prediction of Liver‐Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank
Authors' conclusion
The protein risk score demonstrated superior performance compared with the FIB-4 index and the polygenic risk score in predicting incident LREs among individuals with prediabetes and T2D.
Study context
- Population
- Individuals with prediabetes and T2D, UK Biobank
- Participants
- 13,516 individuals
- Exposure
- 24-protein protein risk score (ProRS) vs FIB-4 vs polygenic risk score for predicting liver-related events (LREs)
- Outcome
- Prediction of incident liver-related events (LREs) (C-index)
- Follow-up
- Median 13.5 years
Methodological detailsprognostic model development with internal validation, LASSO regression
- Prognostic model development with internal validation
- LASSO regression
Main finding
As reported in the abstract
C-index for incident LREs, internal validation set
| Group | Value | C-index |
|---|---|---|
| ProRS | 0.876 (95% CI 0.827–0.920) | 0.876 |
| FIB-4 | 0.733 (95% CI 0.657–0.807) | 0.733 |
| Polygenic risk score | 0.636 (95% CI 0.564–0.706) | 0.636 |
Value
ProRS0.876 (95% CI 0.827–0.920)
FIB-40.733 (95% CI 0.657–0.807)
Polygenic risk score0.636 (95% CI 0.564–0.706)
C-index
ProRS0.876
FIB-40.733
Polygenic risk score0.636
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| 10-year cumulative incidence of LREs by ProRS risk group, training set · 10 yearsHigh riskvs Low risk | 57.1 (31.9–102) | |
| 0.050.21520Hazard ratio (log scale) |
- ProRS C-index, training set
- 0.842 · 95% CI 0.797–0.884
- 10-year cumulative incidence of LREs by ProRS risk group, training set: Low risk 0.2%
- 10-year cumulative incidence of LREs by ProRS risk group, training set: Medium risk 1.2%
- 10-year cumulative incidence of LREs by ProRS risk group, training set: High risk 14.2%
Incident LREs · median follow-up 13.5 years
- Incident LREs
- 171 (1.3%)
- Proteins associated with LRE risk (enriched in inflammatory signalling, extracellular matrix remodelling, complement/coagulation cascades)
- 877
Original publication
Large‐Scale Plasma Proteomics Enhances Prediction of Liver‐Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank. Diabetes Obes Metab. Published 23 July 2026. doi:10.
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