Genetic evidence for the effects of glucokinase activation on frailty‐related outcomes: A Mendelian randomisation study
Main finding · Frailty indexResult — go to the resultBeta per 1% decrease in HbA1c due to GK activation −0.161 95% CI −0.282 to −0.040Authors' conclusion
Our study provides genetic evidence supporting the causal effects of GK activation on lowering the risk of frailty. These findings suggest that GK activators (GKAs) may aid in the management of frailty and sarcopaenia in people with diabetes; however, future randomized controlled trials are necessary to validate these results and establish their clinical applicability.
Study context
- Population
- Genetic proxies: 17 independent single-nucleotide polymorphisms (SNPs) within the GCK gene correlated with HbA1c level17 SNPs
- Comparison
- Genetically proxied glucokinase (GK) activation
- Outcome
- Frailty index
Methodological detailstwo-sample Mendelian randomisation (MR), two-step MR mediation analysis
- Two-sample MR
- Two-step MR mediation analysis
Main finding
As reported in the abstract
Beta per 1% decrease in HbA1c due to GK activation
−0.161
95% CI −0.282 to −0.040
false discovery rate-adjusted p = 0.011
Further findings
Grip strength, ALM, walking pace, telomere length
- GK activation significantly associated with increased grip strength, higher ALM, faster walking pace and longer telomere length
Mediation via CRP
- Significant indirect effect of GK activation on total grip strength and telomere length via reduced CRP; proportion of mediation
- 6.79% to 8.21%
Original publication
Genetic evidence for the effects of glucokinase activation on frailty‐related outcomes: A Mendelian randomisation study. Diabetes Obes Metab. Published 4 March 2025. doi:10.
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