血清胱抑素C水平与2型糖尿病患者视网膜血管直径的相关性研究

Correlation between Serum Cystatin C Level and Retinal Vascular Diameter in Type 2 Diabetes Mellitus

背景糖尿病视网膜病变(DR)是糖尿病常见的微血管并发症之一,目前国内外对DR的筛查主要依赖眼底照相检查,而血清胱抑素C(Cys-C)由于不受年龄、种族及肌肉重量的影响,具有更敏感、更准确的特性,在微血管病变的研究中逐渐受到重视,但关于血清Cys-C与2型糖尿病(T2DM)微血管直径相关性的研究未见报道。目的探讨血清Cys-C水平变化对T2DM患者视网膜血管直径〔视网膜动脉直径(RAE)、视网膜静脉直径(RVE)、视网膜动静脉比值(AVR)〕的影响。方法选取2014年7月-2018年7月于南方医科大学南方医院筛查为T2DM的患者110例,收集患者的临床基线资料及彩色眼底照片,选择患者左眼1.0~1.5 PD范围内的视网膜颞上侧动脉和颞上侧静脉,利用ImageJ软件测量RAE、RVE,计算AVR。分析血清Cys-C水平与临床基线资料的相关性,探讨血清Cys-C水平异常的影响因素及血清Cys-C水平对RAE、RVE、AVR的影响。结果血清Cys-C水平与糖尿病病程、肌酐(Cr)、尿酸(UA)、尿素氮(BUN)呈正相关(rs分别为0.193、0.821、0.501、0.678,P<0.05),血清Cys-C水平与总二氧化碳(CO2)、估算肾小球滤过率(eGFR)呈负相关(rs=-0.281、-0.745,P<0.05)。合并高血压、糖尿病肾病(DN)、DR的T2DM患者血清Cys-C水平高于未合并以上疾病患者(P<0.05)。糖尿病无视网膜病变(NDR)、非增殖期糖尿病视网膜病变(NPDR)、增殖期糖尿病视网膜病变(PDR)的T2DM患者血清Cys-C水平分别为(1.07±0.23)、(1.31±0.64)、(2.12±1.73)mg/L,差异有统计学意义(F=7.245,P=0.002)。二分类Logistic回归分析显示,UA、eGFR是血清Cys-C水平异常的危险因素(P<0.05)。RVE与血清Cys-C水平呈正相关(rs为0.236,P<0.05);AVR与Cr、血清Cys-C水平呈负相关(rs分别为-0.190、-0.299,P<0.05)。有序多分类Logistic回归分析结果显示,吸烟、饮酒、冠心病、血清Cys-C水平异常是RVE增大的危险因素(P<0.05)。血清Cys-C水平预测AVR异常的ROC曲线下面积为0.615〔95%CI(0.508,0.721)〕,血清Cys-C水平预测AVR异常的最佳临界值是1.105 mg/L,约登指数为0.26,灵敏度为0.673,特异度为0.582。结论血清Cys-C水平受UA、eGFR影响;随着血清Cys-C水平的升高,DR的程度越严重,RVE越大、AVR越小,RVE水平与血清Cys-C水平呈正相关,AVR与血清Cys-C水平呈负相关,RAE与血清Cys-C水平无相关关系;当血清Cys-C≥1.105 mg/L,可预测AVR<2/3。

Background Diabetic retinopathy(DR)is a common microvascular complication of diabetes.At present,ophthalmoscopy is the major screening method of DR.By contrast,serum Cystatin C(Cys-C),a more sensitive and accurate screening method as it is not affected by physiological factors such as age,race or muscle weight,is becoming popular in the studies of microangiopathy.However,there has been not any publications about the studies on the diameter of microvessels between serum Cys-C and type 2 diabetes mellitus(T2DM).Objective To study the effect of serum Cys-C level on retinal artery equivalent(RAE),retinal vein equivalent(RVE)and artery-to-vein ratio(AVR)in patients with T2DM.Methods The study retrospectively analyzed the clinical baseline data and color fundus photographs of 110 patients screened for T2DM in Nanfang Hospital,Southern Medical University from July 2014 to July 2018.The retinal vessel diameter in the superior temporal 1.0-1.5 PD range of left eye was measured by ImageJ software.The effect of serum Cys-C level on RAE,RVE and AVR,the correlation between serum Cys-C level and clinical baseline data,the influencing factors of serum Cys-C level abnormality and the influence of serum Cys-C level on RAE,RVE and AVR were analyzed.Results The level of serum Cys-C was positively correlated with the course of diabetes,creatinine(Cr),uric acid(UA)and blood urea nitrogen(BUN)(rs=0.193,0.821,0.501,0.678,P<0.05).The level of serum Cys-C was negatively correlated with total CO2 and estimated glomerular filtration rate(eGFR)(rs=-0.281,-0.745,P<0.05).The level of serum Cys-C in T2DM patients with hypertension,diabetic nephropathy,and DR was significantly higher than that in patients without those diseases(P<0.05).The levels of serum Cys-C in T2DM patients with non-diabetic retinopathy(NDR),nonproliferative diabetic retinopathy(NPDR),and proliferative diabetic retinopathy(PDR)were(1.07±0.23),(1.31±0.64),and(2.12±1.73)mg/L,respectively,which presented a statistically significant difference(F=7.245,P=0.002).Binary Logistic analysis showed that uric acid and eGFR were risk factors for abnormal serum Cys-C(P<0.05).The level of RVE was positively correlated with the level of serum Cys-C(rs=0.236,P<0.05);AVR was negatively correlated with the level of Cr and serum Cys-C(rs=-0.190,-0.299;P<0.05).The results of ordered multi-classification Logistic regression analysis showed that smoking,drinking,coronary heart disease,and abnormal serum Cys-C level were the risk factors for the increase of RVE(P<0.05).The area under the ROC curve for predicting AVR anomalied by serum Cys-C was 0.615〔95%CI(0.508,0.721)〕,while the best critical value for serum Cys-C to predict AVR anomalies was 1.105 mg/L,the Jordan index was 0.26,the sensitivity was 0.673 and the specificity was 0.582.Conclusion The level of serum Cys-C is affected by UA and eGFR.The increase of serum Cys-C level leads to an aggregation of DR,an enlargement of RVE and a diminution of AVR.Therefore,RVE level is positively correlated with serum Cys-C level,AVR level is negatively correlated with serum Cys-C level,but there is no correlation between RAE and serum Cys-C level.When serum Cys-C≥1.105 mg/L,the AVR is predicted to be less than 2/3.