2型糖尿病微血管并发症患者血清miR-152,β_(2)-GPI/ox-LDL和β2-GPⅠ-Lp(a)水平联合检测的价值研究

Clinical Value of Combined Retention of Serum miR-152,β_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)in the Type 2 Diabetes Patients with Microvascular Complications

目的探讨血清miR-152,β_(2)-糖蛋白I氧化低密度脂蛋白复合物(β_(2)-GPI/ox-LDL)和β_(2)-糖蛋白I脂蛋白a复合物[β_(2)-GPⅠ-Lp(a)]水平联合检测对2型糖尿病(type 2 diabetes,T2DM)微血管并发症(type 2 diabetes associated microvascular complications,T2DMC)的诊断价值。方法选取经临床确诊的T2DM患者79例,T2DMC患者78例及体检健康者78例,应用实时荧光定量PCR技术检测血清miR-152的水平,ELISA法检测血清β_(2)-GPI/ox-LDL和β_(2)-GPⅠ-Lp(a)水平,评价上述指标单独或联合检测对于T2DMC的诊断价值。结果血清miR-152,β_(2)-GPI/ox-LDL和β_(2)-GPⅠ-Lp(a)在T2DM患者中分别为44.99(25.71,77.97)fmol/L,0.574(0.376,1.040)U/ml和0.536(0.198,1.056)U/ml,T2DMC患者分别为65.27(43.7,118.1)fmol/L,0.829(0.591,1.138)U/ml和0.597(0.186,1.139)U/ml,均高于健康对照组[13.68(8.14,21.63)fmol/L,0.497(0.196,0.677)U/ml和0.156(0.078,0.476)U/ml],差异有统计学意义(U=616~2192,均P<0.05)。ROC曲线显示,血清miR-152,β_(2)-GPI/ox-LDL和β_(2)-GPⅠ-Lp(a)对T2DMC诊断的曲线下面积(AUC)分别为0.899(95%CI:0.847~0.950),0.785(95%CI:0.716~0.855)和0.718(95%CI:0.637~0.798);三者联合检测对T2DMC的AUC为0.963(95%CI:0.934~0.992)。Spearman秩相关分析显示,血清miR-152,β_(2)-GPI/ox-LDL和β_(2)-GPⅠ-Lp(a)组合与LDL水平呈正相关(r=0.188,P<0.05)。结论血清miR-152联合β_(2)-GP1-ox-LDL,β_(2)-GP1-Lp(a)对于T2DMC诊断具有较高的灵敏度和特异度,可有效弥补单指标检测不足,是T2DMC潜在的辅助诊断标志物。

Objective To evaluate the diagnostic value of combined detection of serum miR-152,β_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)for type 2 diabetes(T2DM)patients with or without microvascular complications.Methods Serum samples of 79 T2DM patients,78 T2DM patients with microvascular complications and 78 healthy controls were obtained from the People’s Hospital of Liuhe in Nanjing and the General Hospital of Eastern Theater Commend,PLA.Serum levels of miR-152,β_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)were examined in those samples using quantitative real-time PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA),respectively.Moreover,level of fasting blood glucose,triglycerides,cholesterol,high density lipoprotein and low density lipoprotein were determined by biochemical analyzer.Results The serum concentrations of miR-152,β_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)were 44.99(25.71,77.97)fmol/L,0.574(0.376,1.040)U/ml and 0.536(0.198,1.056)U/ml in T2DM patients,and 65.27(43.7,118.1)fmol/L,0.829(0.591,1.138)U/mL and 0.597(0.186,1.139)U/ml in T2DMC patients,which were significant higher than that in healthy controls[13.68(8.14,21.63)fmol/L,0.497(0.196,0.677)U/ml and 0.156(0.078,0.476)U/ml,respectively](U=616~2192,all P<0.05).ROC curve analysis results showed that the area of under ROC curve(AUC)of miR-152,β_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)were 0.899(95%CI:0.0.847~0.0.950),0.785(95%CI:0.0.716~0.855)and 0.718(95%CI:0.637~0.798)respectively for T2DM patients with microvascular complications.In the meanwhile,the combination diagnostic value of miR-152,β_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)was 0.963(95%CI:0.934~0.992)for type 2 diabetes patients with microvascular complications,which was markedly useful than any index alone.Moreover,Spearman rank correlation analysis revealed that the combination of miR-152,β_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)were significantly associated with LDL(r=0.188,P<0.05).Conclusion Serum levels of miR-152 combined withβ_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)has high sensitivity and specificity in the discrimination of T2DM patients with microvascular complications,which makes up for the deficiency of individual detection.The increased levles of serum miR-152 combined withβ_(2)-GPI/ox-LDL andβ_(2)-GPⅠ-Lp(a)can be used as novel potential auxiliary diagnosis biomarkers for T2DM patients and T2DM patients with microvascular complications.