血清补体C1q/肿瘤坏死因子相关蛋白3水平对糖尿病肾病代谢参数的影响及其诊断价值研究

Relationships of Serum CTRP3 with Diabetic Nephropathy Associated Metabolic Parameters and Its Diagnostic Value

背景糖尿病肾病(DN)是2型糖尿病(T2DM)严重并发症之一,一些证据表明补体C1q/肿瘤坏死因子相关蛋白3(CTRP3)可能在DN中发挥作用,但目前关于CTRP3与DN的关系尚不明确。目的探讨血清CTRP3水平对DN及其代谢参数的影响。方法选取2017年7月-2018年6月滨州医学院附属医院收治的T2DM患者54例(T2DM组),2型糖尿病肾病患者55例(DN组),并选取55例正常健康体检者作为对照组,三组均进行代谢参数检测,并采用酶联免疫吸附测定法(ELISA)检测CTRP3、白介素6(IL-6)、肿瘤坏死因子-α(TNF-α)、脂联素(APN)水平,比较三组间的差异。采用Pearson相关性分析进行相关性检验,多重线性回归分析探讨各组CTRP3的影响因素,受试者工作特征(ROC)曲线评估CTRP3对DN的诊断价值。结果 T2DM组、DN组IL-6、TNF-α水平高于对照组,DN组IL-6水平高于T2DM组(P<0.05);T2DM组、DN组APN、CTRP3水平低于对照组,DN组CTRP3水平低于T2DM组(P<0.05);女性CTRP3水平高于男性,正常体质量者CTRP3水平高于超重/肥胖者(P<0.05)。多项逻辑回归分析结果显示,CTRP3水平与T2DM[OR=0.804,95%CI(0.731,0.883),P<0.001]和DN[OR=0.730,95%CI(0.654,0.814),P<0.001]的风险之间存在着独立的相关性。Pearson相关性分析结果显示,在对照组中,CTRP3与胰岛素(r=-0.415)、胰岛素抵抗指数(HOMA-IR)(r=-0.438)呈负相关(P<0.05);在T2DM组和DN组中,CTRP3与胰岛素(r=-0.312、-0.407)、HOMA-IR(r=-0.327、-0.436)、糖化血红蛋白(Hb A1c)(r=-0.286、-0.287)、IL-6(r=-0.342、-0.386)和TNF-α(r=-0.359、-0.365)呈负相关,但与肾小球滤过率(e GFR)(r=0.274、0.428)、APN(r=0.436、0.273)呈正相关(P<0.05);在DN组中,CTRP3与肌酐(Cr)(r=-0.389)呈负相关(P<0.05)。多元线性回归分析结果显示,T2DM组中HOMA-IR[β=-64.330,95%CI(-92.067,-9.537)]、APN[β=9.210,95%CI(4.510,16.627)],DN组的HOMA-IR[β=-62.773,95%CI(-122.250,-13.348)]、e GFR[β=0.953,95%CI(0.327,2.442)]是CTRP3的影响因素(P<0.05)。CTRP3诊断DN的ROC曲线下面积(AUC)为0.881[95%CI(0.820,0.943)],灵敏度为76.36%,特异度为90.91%。结论 CTRP3在T2DM和DN患者中明显降低,并与T2DM和DN的风险之间存在着独立的相关性。CTRP3诊断DN具有较高的灵敏度与特异度,在DN的发病机制中具有一定的作用,可作为DN的潜在生物标志物。

Background Diabetic nephropathy(DN)is one of the serious complications of type 2 diabetes mellitus(T2DM).Previous studies have suggested that C1q/TNF-related protein-3(CTRP3)may play a role in the development of DN.However,the relationship between CTRP3 and DN remains unclear.Objective To investigate the relationships of serum CTRP3 with DN and associated metabolic parameters.Methods Fifty-four patients with T2DM(T2DM group),55 with type 2 diabetic nephropathy(DN group)from Binzhou Medical University Hospital,and 55 healthy people(control group)were enrolled from July 2017 to June 2018.The three groups were tested for metabolic parameters.Moreover,ELISA was adopted to detect the concentrations of CTRP3,interleukin 6(IL-6),tumor necrosis factor-α(TNF-α),and adiponectin(APN).Pearson correlation test was used for correlation analysis.Multiple linear regression was used to analyze the influencing factors of CTRP3 in each group.And receiver operating characteristic curve(ROC)was plotted to analyze the ability of CTRP3 in distinguishing disease status.And receiver operating characteristic curve(ROC)was plotted to analyze the ability of CTRP3 in distinguishing DN and T2DM.Results Compared with the control group,serum IL-6 and TNF-αwere significantly increased in T2DM and DN groups,whereas APN and CTRP3 levels were notably decreased(P<0.05).DN group showed higher average IL-6 level but lower average CTRP3 levels than T2DM group(P<0.05).Female and overweight/obesity were associated with higher serum CTRP3 level(P<0.05).Multiple Logistic regression analysis results showed that CTRP3 was independently associated with the risks of T2DM〔OR=0.804,95%CI(0.731,0.883),P<0.001〕and DN〔OR=0.730,95%CI(0.654,0.814),P<0.001〕.Pearson correlation analysis showed that in the control group,CTRP3 was negatively correlated with insulin(r=-0.415)and insulin resistance index(HOMA-IR)(r=-0.438)(P<0.05).CTRP3 was negatively correlated with insulin,HOMA-IR,HbA1c,IL-6 and TNF-αin T2DM group(r=-0.312,-0.327,-0.286,-0.342,-0.359)and in DN group(r=-0.407,-0.436,-0.287,-0.386,-0.365)(P<0.05).CTRP3 also showed a negative correlation with Cr(r=-0.389)in DN group(P<0.05).Moreover,it was positively correlated with eGFR and APN in T2DM group(r=0.274,0.436)and in DN group(r=0.428,0.273)(P<0.05).Besides,multiple linear regression analysis indicated that HOMA-IR〔β=-64.330,95%CI(-92.067,-9.537)〕and APN〔β=9.210,95%CI(4.510,16.627)〕were independently associated with CTRP3 in T2DM group(P<0.05).And HOMA-IR〔β=-62.773,95%CI(-122.250,-13.348)〕and eGFR〔β=0.953,95%CI(0.327,2.442)〕were independently associated with CTRP3 in DN group(P<0.05).The AUC for CTRP3 in the diagnosis of DN was 0.881〔95%CI(0.820,0.943)〕,the sensitivity was 76.36%,and the specificity was 90.91%.Conclusion CTRP3 was significantly reduced in patients with T2DM and DN,and was independently associated with the risks of T2DM and DN,and showed high sensitivity and specificity in the diagnosis of DN,indicating that it may play a role in the pathogenesis of DN and may be used as a potential biomarker for DN.