Prevention & lipidsCohort study
Genetic Predisposition to Low-Density Lipoprotein Cholesterol and Incident Type 2 Diabetes
- Prospective cohort study
- population-based
- UK Biobank
Data collected 2006–2010; analysed March 1 to November 1, 2024
Authors' conclusion
In this cohort study, LDL-C and T2D risks were inversely associated across genetic mechanisms for LDL-C variation.
Study context
- Population
- UK Biobank participants with whole-exome sequencing and genome-wide genotyping
- Participants
- 361,082 participants
- Exposure
- Genetic LDL-C groups
- Outcome
- Incident T2D and CAD
- Follow-up
- Median 13.7 (IQR, 12.9-14.5) years
Main finding
As reported in the abstract
Incident T2D
Hazard ratio (95% CI)
FH
0.65(0.54–0.77)
pLOF
1.48(1.18–1.86)
Very high LDL-C PRS
0.72(0.66–0.79)
High LDL-C PRS
0.87(0.84–0.90)
Low LDL-C PRS
1.13(1.09–1.17)
Very low LDL-C PRS
1.26(1.15–1.38)
- Incident T2D during follow-up
- 22 619 (6.3%)
Observational data: associations, not effects.
Further findings
Incident coronary artery disease (CAD)
- Incident CAD during follow-up
- 17 966 (5.0%)
- CAD risk increased directly with the LDL-C polygenic risk score (PRS)
Original publication
Genetic Predisposition to Low-Density Lipoprotein Cholesterol and Incident Type 2 Diabetes. JAMA Cardiol. Published 1 April 2025. doi:10.1001/jamacardio.2024.5072
Summarised from the published abstract; every number is checked against it