血清晚期糖基化终末产物和血管内皮生长因子水平与2型糖尿病患者视网膜病变的关系

Correlations of serum advanced glycation end products and vascular endothelial growth factor with retinopathy in patients with type 2 diabetes mellitus

目的 观察糖尿病视网膜病变(DR)患者血清晚期糖基化终末产物(AGEs)、血管内皮生长因子(VEGF)水平变化,探讨其与2型糖尿病患者发生DR的关系。方法 2021年1月—2022年12月安阳市人民医院诊治2型糖尿病患者300例,其中104例发生DR者为DR组,196例未发生DR者为无DR组。根据DR分期将104例DR患者分为非增殖期组69例,增殖期组35例。采用ELISA法检测300例患者血清AGEs、VEGF水平。比较DR组与无DR组性别、年龄、糖尿病病程、空腹血糖糖化血红蛋白及血清AGEs、VEGF水平等临床资料;比较非增殖期组与增殖期组血清AGEs、VEGF水平;多因素logistic回归分析2型糖尿病患者发生DR的影响因素;绘制ROC曲线,评估血清AGEs、VEGF对2型糖尿病患者发生DR的诊断效能。结果 (1)DR组糖尿病病程[(7.89±2.21)年]长于无DR组[(6.14±1.96)年](t=7.037,P<0.001),糖化血红蛋白[(9.26±2.34)%]及空腹血糖[(9.57±2.75)mmol/L]水平均高于无DR组[(8.35±2.12)%、(8.64±2.34) mmol/L](t=3.412,P=0.001;t=3.079,P=0.002),性别比例、年龄、体质量指数、收缩压、舒张压及血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇水平与无DR组比较差异均无统计学意义(P>0.05)。(2)DR组血清AGEs[(16.58±5.12)mg/L]、VEGF[(162.54±47.31)ng/L]水平均高于无DR组[(11.89±3.78)mg/L、(105.56±31.28)ng/L](t=9.010,P<0.001;t=12.491,P<0.001)。增殖期组血清AGEs[(18.12±4.25)mg/L]、VEGF[(180.25±42.36)ng/L]水平均高于非增殖期组[(15.80±4.74)mg/L、(153.56±38.98)ng/L](t=2.440,P=0.016;t=3.204,P=0.002)。(3)血清AGEs(OR=1.530,95%CI:1.138~2.056,P=0.005)、VEGF(OR=1.478,95%CI:1.113~1.964,P=0.007)是2型糖尿病患者发生DR的影响因素。血清AGEs、VEGF分别以16.1 mg/L、144.4 ng/L为最佳截断值,诊断2型糖尿病患者发生DR的AUC分别为0.764(95%CI:0.712~0.811,P<0.001)、0.834(95%CI:0.798~0.883,P<0.001),灵敏度分别为55.77%、62.50%,特异度分别为89.80%、92.35%;二者联合诊断2型糖尿病患者发生DR的AUC为0.884(95%CI:0.841~0.918,P<0.001),灵敏度为78.85%,特异度为86.73%。结论 DR患者血清AGEs、VEGF水平升高,其水平升高促进2型糖尿病患者DR的发生、发展,二者联合检测有助于DR的早期筛查。

Objective To observe the changes of serum advanced glycation end products(AGEs) and vascular endothelial growth factor(VEGF) levels in patients with diabetic retinopathy(DR),and to investigate their correlations with DR in patients with type 2 diabetes mellitus(T2DM).Methods In 300 patients with T2DM diagnosed and treated in Anyang People's Hospital from January 2021 to December 2022,there were 104 patients with DR(DR group) and 196 patients with no DR(no-DR group).According to DR stage,DR group was divided into non-proliferative retinopathy group(n=69)and proliferative retinopathy group(n=35).ELISA technique was used to detect the serum levels of AGEs and VEGF in 300patients.The general data as the gender,age,course of diabetes,fasting plasma glucose(FPG),serum glycosylated hemoglobin,AGEs and VEGF were compared between DR group and no-DR group.And the levels of AGEs and VEGF were compared between non-proliferative retinopathy group and proliferative retinopathy group.Multivariate regression model was used to analyze the influencing factors of DR,and ROC curves were plotted to evaluate the diagnostic efficiencies of AGEs and VEGF on diagnosing DR in patients with T2DM.Results(1)The course of diabetes was longer in DR group[(7.89±2.21)years]than that in no-DR group[(6.14±1.96)years](t=7.037,P<0.001),the levels of serum glycosylated hemoglobin and FPG were higher in DR group [(9.26±2.34)%,(9.57±2.75)mmol/L]than those in no-DR group [(8.35±2.12)%,(8.64±2.34)mmol/L](t=3.412,P=0.001;t=3.079,P=0.002),and there were no significant differences in the gender ratio,age,body mass index,systolic blood pressure,diastolic blood pressure,serum total cholesterol,triacylglycerol,low-density lipoprotein cholesterol and high-density lipoprotein cholesterol between two groups(P>0.05).(2)The serum levels of AGEs and VEGF were higher in DR group[(16.58±5.12)mg/L,(162.54±47.31)ng/L]than those in no-DR group[(11.89±3.78)mg/L,(105.56±31.28)ng/L](t=9.010,P<0.001;t=12.491,P<0.001),and were higher in proliferative retinopathy group[(18.12±4.25)mg/L,(180.25±42.36)ng/L]than those in non-proliferative retinopathy group [(15.80±4.74)mg/L,(153.56±38.98)ng/L](t=2.440,P=0.016;t=3.204,P=0.002).(3)The serum AGEs and VEGF levels were the influencing factors of DR in patients with T2DM(OR=1.530,95%CI:1.138-2.056,P=0.005;OR=1.478,95%CI:1.113-1.964,P=0.007).When the optimal cut-off values of serum AGEs and VEGF were16.1mg/L and 144.4ng/L,the AUCs for diagnosing DR in patients with T2DM were 0.764(95%CI:0.712-0.811,P<0.001)and 0.834(95%CI:0.798-0.883,P<0.001),with the sensitivities of 55.77% and 62.50%,and the specificities of 89.80% and 92.35%,respectively.The AUCof combined detection of them two for diagnosing DR was0.884(95%CI:0.841-0.918,P<0.001),with a sensitivity of 78.85% and a specificity of 86.73%.Conclusion The serum levels of AGEs and VEGF are elevated in DR patients,which is correlated with the occurrence and development of DR in patients with T2DM,and the combined detection of them two contributes to the early screening of DR.