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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
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| 篇名： | 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 |
| TITLE： | Investigation of the relationship between metformin and sarcopenia-related traits based on Mendelian randomization |
| 摘要： | 目的 探讨二甲双胍与肌少症相关特征的关联。方法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’sQ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’sQ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。结论二甲双胍可能增加肌少症的风险。 |
| ABSTRACT： | OBJECTIVE To investigate the relationship between metformin and sarcopenia-related traits. METHODS 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 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 Metformin may increase the risk of sarcopenia. |
| 期刊： | 2024年第35卷第22期 |
| 作者： | 朱岳；鞠营辉；杨玉莹；王梦琳；吴睿 |
| AUTHORS： | ZHU Yue，JU Yinghui，YANG Yuying，WANG Menglin，WU Rui |
| 关键字： | 孟德尔随机化；二甲双胍；肌少症；低握力；肌肉质量；关联分析 |
| KEYWORDS： | Mendelian randomization； metformin； sarcopenia； low grip strength； muscle mass； relationship analysis |
| 阅读数： | 6 次 |
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