外周血CCN1与2型糖尿病患者早期肾损伤的相关性研究

Correlation between peripheral blood CCN1 and early renal injury in patients with type 2 diabetes mellitus

目的探讨外周血富含半胱氨酸蛋白61(cysteine-rich protein 61,CCN1)与2型糖尿病患者早期肾损伤的相关性研究。方法回顾性研究河北省石家庄市第二医院2型糖尿病患者321例,以尿液微量白蛋白排泄率(urinary albumin excretion rate,UAER)为金标准,将患者分成将2型糖尿病患者分成早期肾损伤组(n=78,20μg/min≤UAER≤200μg/min)、糖尿病肾病组(n=28,UAER>200μg/min)和正常组(n=215,UAER<20μg/min)。比较3组外周血CCN1表达,Pearson法测定UAER与外周血CCN1的相关性,使用ROC曲线评估外周血CCN1对2型糖尿病早期肾损伤和糖尿病肾病的预测价值。单因素分析基线资料,多因素Logistic回归分析确定早期肾损伤或糖尿病肾病的影响因素。结果糖尿病肾病组CCN1和UAER水平高于早期肾损伤组和正常组;早期肾损伤组的CCN1和UAER水平也高于正常组(P<0.05);外周血CCN1与UAER呈正相关(r=0.916,P<0.001)。以外周血CCN1为检验变量,以是否发生早期肾损伤为状态标量,以敏感度为Y轴,以“1-特异度”为X轴绘制ROC曲线。ROC结果显示,CCN1诊断的临界值为1.59μg/L,其对应的敏感度为85.85%,特异度为73.02%,AUC为0.871(95%CI:0.831~0.903)。以外周血CCN1为检验变量,以是否发生糖尿病肾病为状态标量,以敏感度为Y轴,以“1-特异度”为X轴绘制ROC曲线。ROC结果显示,CCN1诊断的临界值为3.41μg/L,其对应的敏感度为71.43%,特异度为73.72%,AUC为0.761(95%CI:0.707~0.813)。糖尿病肾病组、早期肾损伤组和正常组的病程、高血压、高血脂、收缩压、FPG、糖化血红蛋白(glycated hemoglobin,HbA1c)、尿酸(uric acid,UA)、总胆固醇(total cholesterol,TC)、三酰甘油(triglycerides,TG)和低密度脂蛋白(low-density lipoprotein,LDL)等方面比较差异有统计学意义(P<0.05)。Logistic回归分析结果显示,病程(OR=1.740,95%CI:1.180~2.565)、收缩压(OR=1.943,95%CI:1.267~2.978)、高血脂(OR=1.654,95%CI:1.310~2.088)、FPG(OR=2.776,95%CI:1.260~6.116)、UA(OR=2.228,95%CI:1.174~4.229)和CCN1(OR=3.744,95%CI:1.709~8.200)是2型糖尿病早期肾损伤发生的影响因素(P<0.05)。Logistic回归分析结果显示,病程(OR=1.752,95%CI:1.177~2.609)、收缩压(OR=1.818,95%CI:1.034~3.198)、高血脂(OR=1.680,95%CI:1.320~2.138)、FPG(OR=2.389,95%CI:1.519~3.758)、UA(OR=1.260,95%CI:1.038~1.530)和CCN1(OR=3.815,95%CI:1.636~8.897)是糖尿病肾病发生的影响因素(P<0.05)。结论外周血CCN1与尿液微量白蛋白排泄率呈正相关,是早期肾损伤或糖尿病肾病的危险因素,并可应用于预测早期肾损伤或糖尿病肾病的发生,值得临床进一步研究并推广。

Objective To explore the correlation between peripheral blood cysteine-rich protein 61(CCN1)and early renal injury in patients with type 2 diabetes mellitus(T2DM).Methods A retrospective study was conducted on 321 patients with T2DM in the Second Hospital of Shijiazhuang City.Using the urinary albumin excretion rate(UAER)as the gold standard,the patients were divided into three groups:early renal injury group(n=78,20μg/min≤UAER≤200μg/min),diabetic nephropathy(DN)group(n=28,UAER>200μg/min)and normal group(n=215,UAER<20μg/min).The expression of CCN1 in peripheral blood of the three groups was compared.Pearson method was used to determine the correlation between UAER and CCN1 in peripheral blood,and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of CCN1 in peripheral blood for early renal injury and DN in T2DM patients.Univariate analysis was used to analyze baseline data and multivariate logistic regression analysis was used to determine the influencing factors of early renal injury or DN.Results The levels of CCN1 and UAER in DN group were higher than those in early renal injury group and normal group,and the levels of CCN1 and UAER in the early renal injury group were also higher than those in the normal group(P<0.05).There was a positive correlation between peripheral blood CCN1 and UAER,and the difference was statistically significant(r=0.916,P<0.001).Using peripheral blood CCN1 as the test variable,the ROC curve was plotted with early renal injury as the state scalar,sensitivity as the Y-axis,and"1-specificity"as the X-axis.The ROC results showed that the critical value for CCN1 diagnosis was 1.59μg/L,with a corresponding sensitivity of 85.85%,specificity of 73.02%,and AUC of 0.871(95%CI:0.831-0.903).Peripheral blood CCN1 was used as the test variable,with the occurrence of DN as the state scalar,sensitivity as the Y axis,and"1-specificity"as the X axis to draw the ROC curve.The ROC results showed that the critical value for CCN1 diagnosis was 3.41μg/L,with a corresponding sensitivity of 71.43%,specificity of 73.72%,and AUC of 0.761(95%CI:0.707-0.813).There were significant differences in the course of disease,hypertension,hyperlipidemia,systolic blood pressure(SBP),fasting plasma glucose(FPG),HbA 1c,uric acid(UA),total cholesterol(TC),triglyceride(TG)and low-density lipoprotein(LDL)among the DN group,the early renal injury group and the normal group(P<0.05).Logistic regression analysis showed that the course of disease(OR=1.740,95%CI:1.180-2.565),SBP(OR=1.943,95%CI:1.267-2.978),hyperlipidemia(OR=1.654,95%CI:1.310-2.088),FPG(OR=2.776,95%CI:1.260-6.116),UA(OR=2.228,95%CI:1.174-4.229)and CCN1(OR=3.744,95%CI:1.709-8.200)were the influencing factors of early renal injury in T2DM patients(P<0.05).Logistic regression analysis showed that the course of disease(OR=1.752,95%CI:1.177-2.609),SBP(OR=1.818,95%CI:1.034-3.198),hyperlipidemia(OR=1.680,95%CI:1.320-2.138),FPG(OR=2.389,95%CI:1.519-3.758),UA(OR=1.260,95%CI:1.038-1.530)and CCN1(OR=3.815,95%CI:1.636-8.897)were the influencing factors of DN(P<0.05).Conclusion Peripheral blood CCN1 demonstrates a positive correlation with urinary albumin excretion rate,thereby serving as a risk factor for the onset of early-stage renal injury and DN.It can be used to predict the occurrence of early renal injury or DN,which is worthy of further clinical research and promotion.