Glucokinase activator, circulating metabolites, and cardio-cerebrovascular diseases: a Mendelian randomization study
Authors' conclusion
This study supported the association of GKA with a reduced risk of AF and stroke. The average diameter of very-low-density lipoprotein (VLDL) particles mediated the protective effect of GKA against AF. Further research is needed to clarify the detailed mechanisms of GKA's effects on these metabolites and their translation into reduced CVDs risk, especially considering different ethnic groups.
Study context
- Population
- Large-scale genetic datasets on 168 NMR-measured circulating metabolites and atrial fibrillation (AF), heart failure (HF), coronary artery disease (CAD), myocardial infarction (MI) and stroke; genetic instruments for glucokinase activator (GKA): variants associated with GCK mRNA expression and HbA1c
- Comparison
- Genetically predicted GKA vs no GKA effect
- Outcome
- Causal associations between GKA and CVDs (AF, HF, CAD, MI, stroke)
Methodological detailstwo-sample Mendelian randomization, two-step MR and multivariable MR (MVMR) mediation analyses
- Two-sample Mendelian randomization
- Two-step MR and multivariable MR (MVMR) mediation analyses
Main finding
As reported in the abstract
Genetically predicted GKA and AF: OR (95% CI 0.54, 0.95), P = 0.019
0.71
Genetically predicted GKA and stroke: OR (95% CI 0.96, 0.98), P = 4.82 × 10-5
0.97
Further findings
- Of 168 circulating metabolites, number associated with GKA
- 36
- Metabolites mediating the effect on AF
- 1
Original publication
Glucokinase activator, circulating metabolites, and cardio-cerebrovascular diseases: a Mendelian randomization study. Cardiovasc Diabetol. Published 30 July 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →