Key result
Genetic analyses explore potential effects of ticagrelor on plasma proteins and glucose homeostasis.
Why the study?
Ticagrelor demonstrates additional therapeutic benefits in ACS patients with diabetes, but the underlying mechanisms of this association remain elusive.
Does ticagrelor reduce the risk of diabetes and improve glucose metabolism?
Observational
Does ticagrelor reduce the risk of diabetes and improve glucose metabolism?
Ticagrelor may have non-platelet functions that improve glucose homeostasis and reduce the risk of diabetes, potentially mediated by BDH2 upregulation and enhanced mitochondrial oxidative phosphorylation.
May pinpoint protein mediators of ticagrelor benefit in diabetic ACS; leaves open therapeutic targeting pending validation.
Emerging evidence has demonstrated the additional therapeutic benefits of ticagrelor in acute coronary syndrome (ACS) patients with diabetes. However, the underlying mechanisms of this association remain elusive. Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on ticagrelor, plasma proteomics and type 2 diabetes was employed to identify causal mediator proteins. RNA sequencing (RNA-seq) of ticagrelor-treated HepG2 cells revealed the molecular pathways regulating glucose metabolism. Genetically proxied ticagrelor was significantly associated with a reduced risk of diabetes (OR = 0.859, 95% CI: 0.783–0.934, P = 7.98E-05), and 24.41% of this effect was mediated by upregulation of BDH2 protein. In vitro experiments confirmed the enhanced effect of ticagrelor on glucose consumption. Transcriptome analysis revealed that mitochondrial respiratory chain transfer and oxidative phosphorylation (OXPHOS) were significantly enriched, and genes related to ATP biosynthesis were significantly upregulated. These findings highlight the non-platelet function of ticagrelor in maintaining glucose homeostasis, providing insights into potential drug repurposing in the future.
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Xie et al. (2026) conducted an observational in Glucose Homeostasis Regulation. Ticagrelor was evaluated on Causal effects of ticagrelor on circulating plasma proteins. Genetic and transcriptomic analyses investigated the causal effects of ticagrelor on circulating plasma proteins and glucose homeostasis regulation, though specific results were not provided.
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