Objective To investigate the association between frailty and type 2 diabetes mellitus(T2DM)using a bidirec-tional two-sample Mendelian randomization(MR)analysis,so as to provide the evidence for the prevention and control of frailty and T2DM.Methods Frailty status was assessed using the Fried Frailty Score(FFS),with aggregated data sourced from 386 565 European samples in the UK Biobank.The T2DM data were obtained from the summary results of genome-wide analysis published by the Diabetes Genetics Replication and Meta-analysis Consortium,excluding the UK Biobank data,including 455 313 European samples.Eligible single nucleotide polymorphism site were selected from the FFS and T2DM summary data as instrumental variables.The bidirectional MR analysis was performed using the in-verse-variance weighted method.The heterogeneity was assessed using the modified Cochran Q test.The horizontal plei-otropy of instrumental variables was examined using MR-Egger regression.The robustness of the results was evaluated using the leave-one-out method.The bias was tested using funnel plot.Results The forward MR analysis revealed a statistically significant association between increased FFS and an increased risk of T2DM(OR=2.280,95%CI:1.169-4.447).The reverse MR analysis showed a statistically significant association between T2DM and increased FFS(β=0.026,95%CI:0.012-0.041).Both bidirectional MR results were robust,with no horizontal pleiotropy of the instrumental variables was found(all P>0.5);and the funnel plots did not show significant basis.Conclusion The study found a bi-directional causal association between frailty and T2DM.
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