Objective: To estimate the diagnostic value of fibronectin type Ⅲ-domain containing protein 5 (FNDC5) in subclinical diabetic cardiomyopathy. Methods: A total of 94 patients with type 2 diabetes (T2DM), who were hospitalized from April 2018 to June 2019 in the Third Affiliated Hospital of Soochow University, were enrolled in this study. Patients were divided into T2DM with cardiac dysfunction (subclinical DCM) group (n=47) and T2DM without cardiac dysfunction (non-DCM) group (n=47) according to echocardiography and gated myocardial perfusion imaging results. Basic clinical data and serum FNDC5 level were compared between the two groups. Logistic regression analysis was used to establish predicting models and the diagnostic efficiency of established models was compared by ROC curve analysis. Results: Compared to non-DCM group, patients in subclinical DCM group were older, with longer duration of diabetes, and had higher levels of glycosylated hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) (all P<0.05). Serum FNDC5 level was significantly lower in subclinical DCM group than in non-DCM group (P<0.001). FNDC5 level was positively correlated with ventricular septal e'(r=0.451,P=0.005), mitral valve e'(r=0.291,P<0.001), the ratio of peak early diastolic trans-mitral flow velocity (E) to peak late diastolic trans-mitral flow velocity (A)(r=0.490,P=0.002), while negatively correlated with A(r=-0.399,P<0.001), the average ratio of E/e'(r=-0.490,P<0.001), tricuspid regurgitation velocity(r=-0.567,P<0.001), left atrial volume index(r=-0.491,P<0.001). Univariate ROC analysis showed that the diagnostic efficacy of FNDC5(AUC=0.940,95%CI 0.897-0.982)was superior to age(AUC=0.639,95%CI 0.523-0.752), diabetic duration(AUC=0.663,95%CI 0.555-0.772), HbA1c(AUC=0.740,95%CI 0.638-0.839), TG(AUC=0.661,95%CI 0.547-0.776), TC(AUC=0.675,95%CI 0.563-0.788)and LDL-C(AUC=0.644,95%CI 0.532-0.756). Model 1 was established with subclinical DCM as dependent variable, age, diabetic duration, TG, TC, LDL-C and HbA1c as independent variables. Model 2 was established by adding FNDC5 as independent variable on the basis of model 1. Diagnostic efficacy for subclinical DCM was compared between the two models by ROC analysis. The diagnostic efficiency was better with model 2 (AUC=0.980) than with model 1 (AUC=0.879, P<0.001). When sensitivity was set at 0.617, the specificity of model 2 was higher than that of model 1(0.979 vs. 0.936). When sensitivity was set at 0.532, the sensitivity of model 2 was higher than that of model 1 (1.000 vs. 0.915). Conclusions: Our findings suggest that serum FNDC5 could be used as a novel biomarker for the diagnosis of subclinical DCM.
目的： 探讨Ⅲ型纤维蛋白结构域结合蛋白5（FNDC5）对亚临床型糖尿病心肌病（DCM）的诊断价值。 方法： 该研究为观察性研究。入选2018年4月至2019年6月于苏州大学附属第三医院内分泌科入院的无心血管症状的2型糖尿病患者，根据超声心动图检查和门控心肌灌注显像结果将患者分为亚临床型DCM组和糖尿病不伴心功能不全组（对照组）。收集入选患者的一般临床资料和血FNDC5水平。采用受试者工作特征（ROC）曲线分析比较不同参数和模型的诊断效能。 结果： 研究共入选患者94例，其中亚临床型DCM组47例，对照组47例。与对照组比较，亚临床型DCM组患者年龄更大、糖尿病病程更长、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和糖化血红蛋白（HbA1c）水平更高（P均<0.05）。亚临床型DCM组患者外周血FNDC5表达水平明显低于对照组（P<0.001）。FNDC5水平与亚临床型DCM患者室间隔e′波速度（r=0.451，P=0.005）、二尖瓣环e′波速度（r=0.291，P<0.001）和左心室舒张早期二尖瓣血流速度峰值（E）/二尖瓣心房收缩期血流速度峰值（A）比值呈正相关（r=0.490，P=0.002），而与A值（r=-0.399，P<0.001）、平均E/e′比值（r=-0.490，P<0.001）、三尖瓣峰值流速（r=-0.567，P<0.001）、左心房容积指数（r=-0.491，P<0.001）呈负相关。单因素ROC曲线分析结果显示，FNDC5的诊断效能（AUC=0.940，95%CI 0.897~0.982）优于年龄（AUC=0.639，95%CI 0.523~0.752）、糖尿病病程（AUC=0.663，95%CI 0.555~0.772）、HbA1c（AUC=0.740，95%CI 0.638~0.839）、TG（AUC=0.661，95%CI 0.547~0.776）、TC（AUC=0.675，95%CI 0.563~0.788）和LDL-C（AUC=0.644，95%CI 0.532~0.756）。以是否发生亚临床型DCM作为因变量，以年龄、糖尿病病程、TG、TC、LDL-C和HbA1c作为自变量，构建亚临床型DCM诊断预测模型（模型1），在模型1的基础上引入自变量FNDC5，构建多因素联合预测模型（模型2）。采用ROC曲线比较模型1与模型2的诊断效能，结果示引入FNDC5作为自变量的模型2对于DCM的诊断效能优于模型1（AUC分别为0.980和0.879，P<0.001）。进一步对两个模型的灵敏度和特异度进行比较，发现当灵敏度同为0.617时，模型2的特异度高于模型1（0.979比0.936）；当特异度同为0.532时，模型2的灵敏度高于模型1（1.000比0.915）。 结论： FNDC5联合其他相关基础临床资料对亚临床型DCM具有较好的诊断价值，有望成为诊断亚临床型DCM的生物标志物。.