老年2型糖尿病患者血清Metrnl、E-FABP水平与肌少症的相关性分析.pdf

疑难病杂志 2 0 2 4 年2 月第2 3卷第2 期Chin J Diffic and Compl Cas,February 2024,Vol.23,No.2181D01】10.396 9/j.i s s n.16 7 1-6 450.2 0 2 4.0 2.0 11老年2 型糖尿病患者血清 Metrnl、E-FA BP水平与肌少症的相关性分析论著临床黄雁凌,赵若飞，严翠玲,彭琴,王欢作者单位：430 0 50 武汉，汉阳医院老年病科通信作者：严翠玲，E-mail:【摘要】目的探究血清镍纹样蛋白（Metrml）、上皮型脂肪酸结合蛋白（E-FABP）水平与老年2 型糖尿病（T 2 D M）患者合并肌少症的相关性。方法选取2 0 2 0 年5月一2 0 2 3年7 月武汉市汉阳医院老年病科治疗T2DM患者2 41例为研究对象,根据是否合并肌少症分为肌少症组55例和无肌少症组18 6 例。采用酶联免疫吸附法检测血清Metrnl水平，化学发光免疫分析法检测血清E-FABP水平；比较2 组患者血清Metrml、E-FA BP水平;Pearson相关性分析血清Metrnl、E-FA BP水平与T2DM合并肌少症特征的相关性;受试者工作特征(ROC)曲线分析血清 Metrml、E-FA BP水平预测T2DM 合并肌少症的价值;Logistic 多因素回归分析T2DM 合并肌少症的影响因素。结果肌少症组血清E-FABP、T 2 D M 病程、胰岛素抵抗指数（HOMA-IR）、肌少症-5（SARC-F)评分高于无肌少症组，血清Metrnl、体质量指数（BM I）、步速、握力、四肢骨骼肌质量指数（ASMI）显著低于无肌少症组（t/P=8.839/0.001、5.7 2 3/0.0 0 1、6.116/0.001,28.237/0.001,8.825/0.001,3.605/0.001、2.8 14/0.0 0 5、15.449/0.0 0 1、8.111/0.0 0 1)。血清Metrnl水平与肌少症患者BMI、步速、握力、ASMI呈正相关（r/P=0.512/0.001、0.50 9/0.0 0 1、0.524/0.001、0.498/0.0 0 1），与T2DM病程、HOMA-IR、SA R C-F评分呈负相关（r/P=-0.486/0.001、-0.497/0.001、-0.52 7/0.0 0 1);E-FA BP水平与BMI、步速、握力、ASMI呈负相关（r/P=-0.510/0.001、-0.519/0.001、-0.496/0.0 0 1、-0.494/0.0 0 1）,并且与T2DM病程、HOMA-IR、SA R C-F评分呈正相关（r/P=0.501/0.001、0.50 4/0.0 0 1、0.492/0.0 0 1）。血清Metrml、E-FA BP及二者联合评估T2DM合并肌少症的AUC分别为0.8 16、0.8 2 2、0.8 96,二者联合预测AUC高于Metrnl、E-FA BP单独预测AUC（Z/P=1.96 0/0.0 15、1.97 6/0.0 2 2）。E-FABP升高为T2DM发生肌少症的独立危险因素,Metrnl升高为T2DM发生肌少症的保护因素OR(95%CI）=2.932(1.3476.384）0.7 55(0.6 2 3 0.9 15）,均P0.01。结论老年T2DM合并肌少症患者血清Metrnl水平降低,E-FABP水平升高，二者与肌少症的发生密切相关。【关键词】2 型糖尿病;肌少症;镍纹样蛋白；上皮型脂肪酸结合蛋白;老年人【中图分类号】R587.1;R685Correlation between serum Metrnl,E-FABP levels and myopenia in elderly patients with type 2 diabetesYanling,Zhao Ruofei,Yan Cuiling,Peng Qin,Wang Huan.Department of Geriatrics,Wuhan Hanyang Hospital,Hubei Pro-vine,Wuhan 430050,ChinaCorresponding author:Yan Cuiling,E-mail:791772078 Abstract)Objective To explore the correlation between serum nickel striated protein(Metrnl),epithelial fatty acidbinding protein(E-FABP)levels and myopenia in elderly patients with type 2 diabetes(T2DM).MethodsTwo hundredand forty-one patients with T2DM treated in the geriatric department of Hanyang Hospital in Wuhan from May 2020 to July2023 were selected as the research subjects.They were divided into a sarcopenia group of 55 cases and a non sarcopeniagroup of 186 cases based on whether they were complicated with sarcopenia.Enzyme linked immunosorbent assay wasused to detect serum Metrnl levels,and chemiluminescence immunoassay was used to detect serum E-FABP levels;Com-pare the serum Metml and E-FABP levels between two groups of patients;Pearson correlation analysis of the corelationbetween serum Metrml,E-FABP levels and the characteristics of T2DM with sarcopenia;The value of Receiver OperatingCharacteristic(ROC)curve analysis of serum Metml and E-FABP levels in predicting T2DM with sarcopenia;Logistic multi-ple regression analysis of the influencing factors of T2DM with sarcopenia.Results The serum E-FABP,T2DM course,HOMA-IR,and SARC-F scores in the sarcopenia group were higher than those in the non sarcopenia group,while serum【文献标识码】AsHuang182Metml,body mass index(BMI),gait speed,grip strength,and limb skeletal muscle mass index(ASMI)were lower thanthose in the non sarcopenia group(t/P=8.839/0.001,5.723/0.001,6.116/0.001,28.237/0.001,8.825/0.001,3.605/0.001,2.814/0.005,15.449/0.001,8.111/0.001).The serum Metrml level is positively correlated with BMI,walking speed,grip strength,and ASMI in patients with sarcopenia(r/P=0.512/0.001,0.509/0.001,0.524/0.001,0.498/0.001);It isnegatively correlated with the course of T2DM,HOMA-IR,and SARC-F scores(r/P=-0.486/0.001,-0.497/0.001,-0.527/0.001);The level of E-FABP is negatively correlated with BMI,walking speed,grip strength,and ASMI(r/P=-0.510/0.001,-0.519/0.001,-0.496/0.001,-0.494/0.001);There is a positive correlation between the course ofT2DM,HOMA-IR,and SARC-F scores(r/P=0.501/0.001,0.504/0.001,0.492/0.001).The AUC of T2DM with sarcope-nia evaluated by serum Metrnl,E-FABP,and their combination were 0.816,0.822,and 0.896,respectively.The combined pre-diction of AUC was higher than that of Metrnl and E-FABP alone(Z=1.960,1.976,P=0.015,0.022).Elevated E-FABP is anindependent risk factor for sarcopenia in T2DM,while elevated Metml is a protective factor for sarcopenia in T2DM OR(95%CI)=2.932(1347-6.384),0.755(0.623-0.915),all P0.05），具有可比性。本研究已经获得医院伦理委员会批准（2 0 2 0 0 412 0 6 11），患者或家属知情同意并签署知情同意书。1.2病例选择标准（1)纳入标准:T2DM及肌少症均符合诊断标准5-6 ;患者年龄6 0 岁;临床信息记录完整者。（2)排除标准：有脏器损伤、恶性肿疑难病杂志 2 0 2 4 年2 月第2 3卷第2 期Chin J Diffic and Compl Cas,February 2024,Vol.23,No.2瘤、免疫系统疾病、感染或传染性疾病、血液系统疾病者；有激素应用史或减肥药物服用史者;有骨关节疾病者;1 型糖尿病或其他类型糖尿病及糖尿病并发症者。1.3观测指标与方法1.3.1基线资料收集：性别、年龄、高血压史、冠心病史、吸烟史、饮酒史、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）、糖化血红蛋白（HbAle）、空腹血糖（FPG）、T2DM病程、胰岛素抵抗指数（HOMA-IR）、体质量指数（BMI）、步速、握力等。其中HOMA-IR=FPG(mmol/L）空腹胰岛素(FINS)（U/ml)/22.5。1.3.2血清Metrnl、E-FA BP水平检测：采集入组时T2DM患者空腹外周静脉血样5ml,室温下静置30 60min后离心收集上清液，避光8 0 冰箱保存待测。采用酶联免疫吸附法检测血清Metrnl水平，化学发光免疫分析法检测血清E-FABP水平，试剂盒购自上海富雨生物科技有限公司（货号FY-04196H2）、南京赛泓瑞生物科技有限公司（货号SCB985Hu）。1.4肌少症评估应用中文版肌少症-5（sarcopenia-five,SARC-F)评分，包括行走辅助、爬台阶、从椅子上坐起、跌倒、力量等5个项目，每项分值0 2 分，总分10分,SARC-F评分4分则为可疑肌少症患者。四肢骨骼肌质量指数（appendicular skeletal muscle massindex，A SM I）=四肢骨骼肌质量（kg）/身高（m）,四肢骨骼肌质量采用拜斯倍斯医疗器械贸易有限公司生产的Inbody 770型人体成分分析仪检测,当男性ASMI7.0kg/m,女性ASMI5.7kg/m;男性握力 2 8.0kg,女性握力 18.0 kg;SARC-F评分4分则诊断为肌少症。疑难病杂志 2 0 2 4 年2 月第2 3 卷第2 期Chin J Diffic and Compl Cas,February 2024,Vol.23,No.21.5统计学方法采用SPSS25.0软件进行统计学分析。符合正态分布的计量资料以（xs)表示,2 组比较行独立样本t检验；计数资料以频数或率（%）表示,2 组比较行x检验；Pearson相关性分析血清Metrml、E-FA BP水平与T2DM合并肌少症特征的相关性;受试者工作特征（receiver operating characteristic，ROC）曲线评估血清Metrml、E-FA BP水平在T2DM合并肌少症中的预测价值，曲线下面积（area undercurve,AUC)比较采用Z检验；采用Logistic 多因素回归分析T2DM合并肌少症的影响因素。P0.05）。肌少症组T2DM 病程、HOMA-IR、SA R C-F评分高于无肌少症组,BMI、步速、握力、ASMI低于无肌少症组(P0.05),见表1。表1无肌少症组与肌少症组患者临床资料比较Tab.1(Comparison of clinical data between patients without sar-copenia and those with sarcopenia项目男性例(%)年龄(元s,岁)T2DM 病程(xs,年)BMI(xs,kg/m)高血压史例(%)冠心病史例(%)吸烟史例(%)饮酒史例(%)TC(x s,mmol/L)HDL-C(xs,mmol/L)LDL-C(xs,mmol/L)TG(x s,mmol/L)HbAic(xs,%)FPC(x s,mmol/L)HOMA-IR(xs)步速(xs,m/s)握力(xs,kg)SARC-F评分(xs,分)ASMI(xs,kg/m)2.22组患者血清Metrnl、E-FA BP水平比较症组血清E-FABP水平高于无肌少症组,Metrnl 水平低于无肌少症组（P0.01）,见表2。183表2 无肌少症组与肌少症组患者血清Metrnl、E-FA BP水平比较(xs,ng/L)Tab.2Comparison of serum Metrnl and E-FABP levels betweenpatients with muscle atrophy and those without muscle at-rophy组别例数无肌少症组186肌少症组55值P值2.3血清Metrnl、E-FA BP水平与T2DM合并肌少症特征的相关性Pearson相关性分析结果显示,T2DM合并肌少症患者血清Metrnl水平与BMI、步速、握力、ASMI呈正相关,与T2DM 病程、HOMA-IR、SA R C-F评分呈负相关(P0.01);E-FABP水平与BMI、步速、握力、ASMI呈负相关，与T2DM病程、HOMA-IR、SA R C-F评分呈正相关(P0.01）,见表3。表3血清Metrnl、E-FA BP水平与T2DM合并肌少症特征的相关性Tab.3Correlation between serum Metrnl,E-FABP levels andcharacteristics of T2DM with sarcopenia无肌少症组肌少症组/X值P值(n=186)(n=55)97(52.15)29(52.73)75.42 6.8975.07 6.4512.36 4.1016.42 6.0823.36 2.3122.10 2.16106(56.99)32(58.18)56(30.11)17(30.91)90(48.39)25(45.45)29(15.59)8(14.55)6.24 1.216.28 1.270.91 0.190.88 0.203.74 0.493.76 0.451.70 0.411.71 0.457.98 2.018.13 2.166.48 2.077.02 2.192.16 0.622.71 0.450.85 0.120.80 0.1035.42 3.7926.14 4.313.01 0.505.13 0.457.12 1.395.43 1.24Metrnl147.62 20.54120.16 19.338.8250.001Metrnl指标厂值T2DM病程0.4860.006 0.9400.3360.7375.7230.0013.6050.0010.0250.8750.0130.9100.1460.7020.0360.8500.2130.8321.0160.3100.2710.7870.1550.8770.4780.6331.6770.0956.1160.0012.8140.00515.4490.00128.2370.0018.111 0.001 肌少评分、BMI、步速、握力、ASMI为自变量进行Logistic多因素回归分析,结果显示,高E-FABP为影响T2DM合并肌少症的独立危险因素,高Metrnl 为影响 T2DM 合E-FABP529.78 66.12624.91 82.358.8390.001E-FABPP值值P值0.0010.501HOMA-IR0.497SARC-F评分-0.527BMI0.512步速0.509握力0.524ASMI0.4982.4血清Metrnl、E-FA BP水平预测T2DM合并肌少症的价值绘制血清Metrnl、E-FA BP水平预测T2DM合并肌少症价值的ROC曲线,并计算AUC,结果显示：血清Metrnl、E-FA BP及二者联合预测T2DM合并肌少症的AUC分别为0.8 16、0.8 2 2、0.8 96，二者联合预测AUC高于Metrnl、E-FA BP单独预测AUC(Z=1.960、1.976,P=0.015、0.0 2 2),见表4、图1。2.5T2DM 合并肌少症影响因素的 Logistic 多因素回归分析以T2DM患者是否合并肌少症（是=1,否=0)为因变量,以上述结果中差异有统计学意义的连续变量Metrnl、E-FA BP、T 2 D M 病程、HOMA-IR、SA R C-F0.0010.0010.5040.0010.4920.001:0.5100.001-0.5190.0010.4960.0010.4940.0010.0010.0010.0010.0010.001?184并肌少症的保护因素（P0.01）,见表5。表4血清Metrnl、E-FA BP水平预测T2DM合并肌少症的价值比较Tab.4 Comparison of serum Metrnl and E-FABP levels in predic-ting sarcopenia in T2DM patientsYouden变量Cut-off值Metrnl592.20 ng/L 0.822 0.762 0.882 0.728二者联合0.896 0.836 0.946 0.9091.0F0.80.60.40.20图1血清Metml、E-FA BP水平评估T2DM合并肌少症的ROC曲线Fig.1 ROC curve of serum Metrnl and E-FABP levels in evalua-ting T2DM with sarcopenia表5T2DM合并肌少症影响因素的Logistic多因素回归分析Tab.5 Logistic multiple regression analysis of the influencing fac-tors of T2DM complicated with sarcopenia项目值SE值Wald值P值 OR值95%CIMetrnl高-0.2810.0988.2240.004 0.755 0.623 0.915E-FABP 高1.076 0.397T2DM病程0.025 0.224HOMA-IR 高0.176 0.154SARC-F评分高0.195 0.186BMI高0.148 0.157步速慢0.116 0.109握力低0.14300.2880.2470.619 1.154 0.656 2.029ASMI高0.072 0.2683 讨 论T2DM 患者体内糖脂代谢紊乱、胰岛素抵抗增加，,肌肉内蛋白质的分解和合成平衡被破坏，可能增加肌少症的患病率 7 8 。此外,T2DM 患者体内氧化应激和炎性反应水平增加会影响线粒体功能,造成三磷酸腺疑难病杂志 2 0 2 4 年2 月第2 3卷第2 期Chin J Diffic and Compl Cas,February 2024,Vol.23,No.2苷合成障碍,使得氧自由基过度增加,同样可能导致肌少症的发生 。而肌少症不仅显著增加老年患者残疾风险,同时还可能与呼吸系统、心血管系统功能损害有关 10-1。因此,临床需早期明确T2DM患者肌少症的发生,预防性用药。Metrnl可通过急性运动和冷暴露在骨骼肌和脂肪AUC95%CI敏感度特异度指数0.9040.5220.8020.5290.7880.698一Metrnl-E-FABP二者联合一参考线10.20.41-特异度7.3420.007 2.932 1.347 6.3840.0120.912 1.025 0.661 1.5901.3010.254 1.192 0.881 1.6121.0960.2951.215 0.844 1.7490.8940.344 1.160 0.853 1.5781.1330.287 1.123 0.907 1.3900.0730.787 1.075 0.636 1.818组织中被诱导,循环中Metrnl水平的增加可通过刺激米色/棕色脂肪细胞的产热和骨骼肌中抗炎细胞因子的产生来提高胰岛素敏感性 12 。此外,既往研究发现Metrnl丢失还可能导致受损的肌肉中抗炎表型改变、免疫细胞减少 13。Cai 等 14 发现,血清Metrml 与老年慢性心力衰竭患者体质量减轻有关。Baht等 15 研究证明,Metrnl由巨噬细胞分泌,能通过抑制炎性反应和诱导胰岛素样生长因子1促进肌肉再生。基于本研究结果中血清Metrnl在合并和未合并肌少症患者中的差异表达及既往研究推测，T2DM患者体内炎性反应和氧化应激增加导致巨噬细胞分泌Metrnl量减少，循环中血清Metrnl检测水平较低,Metrnl 的降低导致其调节肌肉损伤和促进肌肉再生作用减弱，肌少症合并风险增加;此外,Metrnl 水平降低使其提高胰岛素敏感0.60.81.0性的功能被抑制,T2DM疾病进一步发展,糖脂代谢紊乱及胰岛素抵抗进一步加剧，肌肉内蛋白质合成和分解平衡进一步被破坏,推动肌少症的发生发展。E-FABP主要表达于表皮骨骼肌、脑、脊髓等组织中,参与细胞内信号转导、代谢、脂肪酸运输,在动脉粥样硬化的发生发展中发挥重要作用 16 。吴秀成等 1研究显示,E-FABP与多囊卵巢综合征患者糖脂代谢有关。Tanabe 等 18 研究结果显示,自发性糖尿病肌少症大鼠尿液中肝型FABP(L-FABP)水平显著升高,尿L-FABP反映肌肉力量和重量,可监测糖尿病肌少症的进展。然而E-FABP与T2DM合并肌少症的关系仍不明确。本研究血清E-FABP在合并肌少症的患者中高表达,且影响肌少症的发生。分析认为E-FABP水平增加可能与T2DM 患者体内炎性反应和氧化应激增加、血管损伤等作用有关，而E-FABP水平升高后会进一步打乱T2DM 患者的糖脂代谢平衡,推动疾病进展，增加肌少症发生风险 19 。HOMA-IR是反映糖尿病患者体内葡萄糖代谢水平的重要指标,其异常升高代表患者体内糖代谢乱 2 0-2 1。SARC-F评分是筛查肌少症的重要评分工具,在多种共识中被建议使用,可对筛查出的肌少症可疑患者进行肌量和肌肉检查 2 2 。ASMI 是根据四肢骨骼肌质量和身高计算得出的人体肌量评估标准，可有效评估肌少症 2 3。而本研究中Metrnl、E-FA BP与上疑难病杂志 2 0 2 4 年2 月第2 3卷第2 期Chin J Diffic and Compl Cas,February 2024,Vol.23,No.2述指标的相关性反映了Metrnl、E-FA BP与糖代谢紊乱、胰岛素抵抗间的相互促进,影响老年T2DM患者肌量和肌肉,共同参与肌少症的发生发展。ROC 曲线结果显示Metrnl、E-FA BP对老年T2DM患者合并肌少症均具有一定评估价值，且联合评估可增加AUC,表明联合后可为临床提供更为精确的参考信息。综上，老年T2DM患者血清E-FABP水平增加、Metrnl水平降低与肌少症的发生密切相关,二者升高分别是肌少症发生的危险因素和保护因素。血清Metrnl、E-FA BP联合可有效评估肌少症，临床可通过监测T2DM 患者血清 Metrnl、E-FA BP水平对肌少症进行预防和治疗。但由于本研究未对血清 Metrnl、E-FABP水平进行动态监测,且二者参与肌少症发生的具体生物机制仍未阐明，因此仍需更大样本量的研究以及基础实验验证。利益冲突：所有作者声明无利益冲突作者贡献声明黄雁凌：研究设计、文章撰写；赵若飞：数据收集、文章审核；严翠玲、彭琴、王欢：数据收集、统计学分析参考文献1Yuan S,Larsson SC.Epidemiology of 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