Metabolic signatures of lipid dysregulation and inflammation characterize pancreatic cancer risk in type 2 diabetes mellitus and improve risk stratification: a prospective cohort study
Authors' conclusion
Lipid dysregulation and inflammation statistically account for a substantial proportion of the T2DM-PC association. The MRS captures these molecular alterations, serving as a preliminary tool to improve long-term PC risk stratification, which warrants rigorous external validation before clinical application.
Study context
- Population
- UK Biobank participants with NMR metabolomics
- Participants
- 445,931 participants
- Exposure
- T2D vs no T2D; Metabolic risk score (MRS) highest vs lowest tertile
- Outcome
- Pancreatic cancer risk
- Follow-up
- 13.6-year follow-up
Methodological detailsUK Biobank, NMR metabolomics, early pancreatic cancer (PC) cases excluded
- UK Biobank
- NMR metabolomics
- Early PC cases excluded
Main finding
As reported in the abstract
T2D increased PC risk, HR
1.40 (1.18-1.67) (95% CI)
Candidate metabolites statistically accounting for a significant proportion of the T2D-PC association, mainly lipid dysregulation (TG-enriched VLDL) and inflammation (GlycA)
30
Observational data: associations, not effects.
Further findings
MRS and long-term PC risk
- Highest vs lowest MRS tertile, HR
- 1.79
- MRS derived by LASSO in T2D sub-cohort
15-year PC prediction: MRS added to clinical factors
- AUC increased from 72.3% to 75.8%
- P < 0.001
Original publication
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