晶状体内晚期糖基化终末产物与2型糖尿病相关性的多中心应用研究

A multicenter study of the correlation between advanced glycation end products in the lens and type 2 diabetes

目的:探讨晶状体内晚期糖基化终末产物(AGE)与2型糖尿病的相关性。方法:于2018年8月14日至9月14日在中南大学湘雅医院、长沙市第三医院、长沙市第四医院内分泌科招募受试者226例,以OGTT试验结合临床表现为金标准,对同一受试者使用晶状体AGE荧光检测与金标准两种方法筛查2型糖尿病。绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC)及其95%CI,计算AGE诊断2型糖尿病的灵敏度、特异度、约登指数、Kappa值及其95%CI,并根据约登指数确定最佳截断值。以是否糖尿病为结局指标,AGE为二分类指标,构建三个logistic回归模型,分析AGE与糖尿病之间的关系。按照年龄和分中心分层,比较AGE阴性组和阳性组之间空腹血糖和餐后2 h血糖之间的差异。结果:ROC曲线下面积为0.86(95%CI:0.81~0.91)。根据约登指数选取AGE最佳截断点为0.24,此时,灵敏度为82.86(95%CI:77.81~87.91)、特异度为77.06(95%CI:71.43~82.7)、约登指数为59.92(95%CI:53.36~66.49),Kappa值为79.62(95%CI:74.22~85.02)。除20~39岁组外,不同年龄段、不同分中心、总人群AGE阳性组空腹血糖及餐后2 h血糖均高于AGE阴性组,均P<0.05。调整年龄、性别、分中心的混杂影响后(模型三),与AGE阴性组相比,AGE阳性组患糖尿病的相对风险为11.75倍(95%CI:5.61~24.60),均P<0.001。结论:晶状体内AGE与2型糖尿病患病风险相关性较高,AGE截断点在0.24时,具有较高的灵敏度和特异度,可作为2型糖尿病早期筛查的实用工具。

Objective To investigate the relationship between advanced glycation end products(AGEs)in the lens and type 2 diabetes mellitus.Methods 226 subjects were recruited between August 14 to September 14,2018 from the Endocrinology Department of Central South University Xiangya Hospital,the Third Hospital of Changsha City,and the Fourth Hospital of Changsha City.The OGTT test,combined with clinical indicators,were used as the gold standard.Subjects were screened for type 2 diabetes using both the lens AGE fluorescence assay and the gold standard.Drawing the receiver operating characteristic(ROC)curve,we calculated the area under the curve(AUC)and its 95%CI and calculated the AGE for the diagnosis of type 2 diabetes.Sensitivity,specificity,Youden index,Kappa value,and its 95%CI,and the optimal cut-off value were determined according to the Youden index.Taking diabetes as the outcome indicator and AGE as the binary indicator,three logistic regression models were constructed.Stratified by age and sub-center,the differences between fasting blood glucose and 2 h postprandial blood glucose were compared between the AGE-negative and AGE-positive groups to determine the relationship between AGE and diabetes.Results The area under the ROC curve was 0.86(95%CI:0.81-0.91).According to the Youden index,the optimal cut-off point for AGE was 0.24.At this time,the sensitivity was 82.86(95%CI:77.81-87.91),the specificity was 77.06(95%CI:71.43-82.7),the Youden index was 59.92(95%CI:53.36-66.49),the Kappa value was 79.62(95%CI:74.22-85.02).Except for the 20-39-year-old group,the fasting blood glucose and 2 h postprandial blood glucose of the AGE-positive group in different age groups,different sub-centers,and the general population were higher than those of the AGE-negative group(all P<0.05).After adjusting for the confounding effects of age,gender,and sub-center(model 3),the relative risk of diabetes in the AGE-positive group was 11.75 times higher than the AGE-negative group(95%CI:5.61-24.60),all with P<0.001.Conclusion There was a high correlation between AGE in the lens and the risk of type 2 diabetes.When the cut-off point of AGE is 0.24,it had high sensitivity and specificity and could be used as a practical tool for early screening of type 2 diabetes.