2型糖尿病患者血清中血管内皮生长因子、apelin及血红素氧合酶-1水平变化及其与糖尿病视网膜病变的相关性研究
Changes of serum vascular endothelial growth factor, apelin and heme oxygenase-1 levels in patients with type 2 diabetes mellitus and their relationship with diabetic retinopathy
摘要目的 观察2型糖尿病(T2DM)患者血清中VEGF、apelin、血红素氧合酶-1(HO-1)水平变化,初步探讨其与糖尿病视网膜病变(DR)的相关性.方法 回顾性病例研究.2014年1月至2017年12月在海南西部中心医院内分泌科住院治疗的T2DM患者208例纳入研究.均行视力、裂隙灯显微镜、间接检眼镜、FFA检查.根据检查结果同时结合DR临床诊断标准,将患者分为无DR(NDR)组、非增生型DR(NPDR)组、增生型DR(PDR)组,分别为72、76、60例.选取同期健康体检者50名作为对照组.采用全自动生化分析仪测定受检者空腹血糖、糖化血红蛋白、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平;ELISA测定血清中VEGF、apelin、HO-1水平.受试者工作特征曲线(ROC曲线)分析VEGF、apelin、HO-1预测PDR发生的价值.Pearson相关分析PDR患者血清VEGF、apelin、HO-1与各临床指标的相关性.结果 PDR组、NPDR组、NDR组、对照组受检者血清中VEGF分别为(56.82±10.16)、(91.74±22.83)、(140.15±36.40)、(195.28±42.26) pg/ml,apelin分别为(2.95±0.53)、(4.68±0.74)、(7.25±1.13)、(10.16±1.35) ng/ml,HO-1分别为(50.37±10.14)、(43.58±8.16)、(30.25±6.28)、(22.60±4.72) mmol/L;与NPDR组、NDR组、对照组受检者比较,PDR组患者血清VEGF(F=17.306)、apelin(F=21.814)明显升高,HO-1(F=15.827)明显降低,差异均有统计学意义(P<0.05).ROC曲线分析显示,血清VEGF、apelin、HO-1水平预测PDR的临界值分别为162.50 pg/ml、8.30 ng/ml、27.13 mmol/L;3项联合预测PDR的ROC曲线下面积为0.906(95%CI 0.849~0.962),其灵敏度和特异性分别为90.3%、83.0%.Pearson相关分析结果显示,PDR患者血清VEGF、apelin、HO-1与糖尿病病程(r=0.382、0.416、-0.36)、FPG(r=0.438、0.460、-0.397)、HbAlc(r=0.375、0.478、-0.405)相关(P<0.05),且血清VEGF与apelin、HO-1均呈明显相关(r=0.793、-0.594,P<0.01).结论 DR患者血清VEGF、apelin水平升高,HO-1水平降低,且与DR进展相关;VEGF、apelin、HO-1联合检测有助于预测PDR的发生.
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abstractsObjective To observe the serum vascular endothelial growth factor (VEGF),apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR).Methods A total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study.Vision,slit lamp microscope,indirect ophthalmoscope and FFA examinations were performed on all the subjects.According to the results of the examinations combined with the DR clinical staging criteria,the patients were divided into non-DR (NDR) group,non-proliferative DR (NPDR) group,and proliferative DR (PDR) group,with 72,76 and 60 patients in each,respectively.The clinical data of each group were recorded,and the levels of fasting blood glucose (FPG),HbA1c,total cholesterol (TC),three acylglycerol (TG),high density lipoprotein (HDL-C),low density lipoprotein (LDL-C),VEGF,apelin and HO-1 were detected in each group.The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF,apelin and HO-1 in predicting the occurrence of PDR.Correlation analysis of serum VEGF,Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis.Results The level of VEGF (56.82± 10.16 vs 91.74±22.83,140.15±36.40,195.28±42.26 pg/ml)and apelin (2.95±0.53 vs 4.68±0.74,7.25±1.13,10.16± 1.35 ng/ml) in PDR group were significantly higher than those in NPDR,NDR and control groups (F=17.306,21.814;P<0.05).The level of HO-1 (50.37±10.14 vs 43.58±8.16,30.25t6.28,22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR,NDR and control groups (F=15.827,P<0.05).The ROC curve analysis showed that the best cut-offvalues of serum VEGF,apelin and HO-1 were 162.50 pg/ml,8.30 ng/ml,27.13 mmol/L,and the three combined to predict PDR of AUC (95%CI)was 0.906 (0.849-0.962),and their sensitivity (90.3%) and specificity (83%) were better.The correlation analysis showed that the VEGF,apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382,0.416,-0.36;P<0.05),FPG (r=0.438,0.460,-0.397;P<0.05) and HbAlc (r=0.375,0.478,-0.405;P<0.05),and the serum VEGF were correlated with apelin and HO-1 (r=0.793,-0.594;P<0.01).Conclusion Elevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR,and the three combination helps predict the occurrence of PDR.
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