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中国科学技术大学附属第一医院离子医学中心(合肥离子医学中心),合肥 230088
Received:14 December 2023,
Revised:2024-07-19,
Accepted:21 July 2024,
Published:30 November 2024
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朱岳,鞠营辉,杨玉莹,等.基于孟德尔随机化探讨二甲双胍与肌少症相关特征的关联[J].中国药房,2024,35(22):2793-2798.
ZHU Yue,JU Yinghui,YANG Yuying,et al.Investigation of the relationship between metformin and sarcopenia-related traits based on Mendelian randomization[J].ZHONGGUO YAOFANG,2024,35(22):2793-2798.
朱岳,鞠营辉,杨玉莹,等.基于孟德尔随机化探讨二甲双胍与肌少症相关特征的关联[J].中国药房,2024,35(22):2793-2798. DOI: 10.6039/j.issn.1001-0408.2024.22.16.
ZHU Yue,JU Yinghui,YANG Yuying,et al.Investigation of the relationship between metformin and sarcopenia-related traits based on Mendelian randomization[J].ZHONGGUO YAOFANG,2024,35(22):2793-2798. DOI: 10.6039/j.issn.1001-0408.2024.22.16.
目的
2
探讨二甲双胍与肌少症相关特征的关联。
方法
2
基于公开的全基因组关联研究相关数据库,利用与二甲双胍使用强相关的单核苷酸多态性位点作为工具变量,采用两样本孟德尔随机化(MR)分析方法[包括逆方差加权(IVW)法、MR-Egger回归法和加权中位数法
]
研究二甲双胍与肌少症3种相关特征(低握力、肌肉质量、步行速度)的关联。分别采用Cochran’s
Q
检验评估异质性、MR-Egger截距检验检测多效性、留一法进行敏感性分析。
结果
2
IVW法分析结果显示,二甲双胍的使用可能与低握力风险增加(
β
=1.550,95%CI为0.389~2.711,
P
=0.009)和四肢肌肉质量减少(右腿瘦体重:
β
=-0.665,95%CI为-1.018~-0.312,
P
<0.001;左腿瘦体重:
β
=-0.710,95%CI为-1.049~-0.371,
P
<0.001;右臂瘦体重:
β
=-0.471,95%CI为-0.890~-0.053,
P
=0.027;左臂瘦体重:
β
=-0.463,95%CI为-0.865~-0.061,
P
=0.024)存在显著关联,但与步行速度无关。其他2种方法的结果或因果效应方向与之一致。Cochran’s
Q
检验提示本研究结果存在一定异质性;MR-Egger截距检验未发现水平多效性;敏感性分析提示本研究结果具有稳健性。
结论
2
二甲双胍可能增加肌少症的风险。
OBJECTIVE
2
To investigate the relationship between metformin and sarcopenia-related traits.
METHODS
2
Based on the data from publicly genome-wide association study-related databases, using single nucleotide polymorphisms strongly associated with metformin as instrumental variables, the two-sample Mendelian randomization (MR) analysis methods [inverse variance weighting (IVW) method, MR-Egger regression method and weighted median estimator method
]
were employed to investigate the relationship between metformin and three sarcopenia-related traits (low grip strength, muscle mass and walking speed). Cochran’s
Q
test was used to assess heterogeneity, MR-Egger intercept test was used to detect horizontal pleiotropy, and leave-one-out analysis was performed for sensitivity analysis.
RESULTS
2
The results of IVW method showed that metformin use was significantly associated with an increased risk of low grip strength (
β
=1.550, 95%CI was 0.389-2.711,
P
=0.009) and reduced limb muscle mass (right leg lean body mass:
β
=-0.665, 95%CI was -1.018--0.312,
P
<0.001; left leg lean body mass:
β
=-0.710, 95%CI was -1.049--0.371,
P
<0.001; right arm lean body mass:
β
=-0.471, 95%CI was -0.890--0.053,
P
=0.027; left arm lean body mass:
β
=-0.463, 95%CI was -0.865--0.061,
P
=0.024),but was not associated with walking speed. The results or causal effects of the other two methods are consistent with it. The Cochran’s
Q
test indicated some degree of heterogeneity in the result of this study. No horizontal pleiotropy was detected by the MR-Egger intercept test. The sensitivity analysis suggested that the results of this study were stable.
CONCLUSIONS
2
Metformin may increase the risk of sarcopenia.
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