中国全科医学 ›› 2020, Vol. 23 ›› Issue (8): 913-919.DOI: 10.12114/j.issn.1007-9572.2020.00.039

• 专题研究 • 上一篇    下一篇

皮肤无创晚期糖基化终末产物测定在社区2型糖尿病血管性并发症筛查中的作用研究

邢美艳1,姜天1,夏莉1,张一1,许娟1,罗莉1,胡红琳1,赵广碧2,刘勇3,王贻坤3,夏营威3,章秋1*   

  1. 1.230022安徽省合肥市,安徽医科大学第一附属医院内分泌科 2.230022安徽省合肥市,安徽医科大学第一附属医院内分泌科实验室 3.230022 安徽省合肥市,中国科学院合肥物质科学研究院
    *通信作者:章秋,教授,主任医师,博士研究生导师;E-mail:aynfmk@163.com
  • 出版日期:2020-03-15 发布日期:2020-03-15
  • 基金资助:
    基金项目:安徽省科技重大项目(17030901017);安徽省重点研究和开发计划(1804h08020262);2017年安徽省高校自然科学研究项目(产学研重大项目)(KJ2017ZD19);安医大一附院2018年度国家自然科学基金青年科学基金培育计划项目(2018kj20)

Value of Advanced Glycation End-products in Skin Measured Noninvasively in Community-based Screening of Type 2 Diabetes-related Vascular Complications 

XING Meiyan1,JIANG Tian1,XIA Li1,ZHANG Yi1,XU Juan1,LUO Li1,HU Honglin1,ZHAO Guangbi2,LIU Yong3,WANG Yikun3,XIA Yingwei3,ZHANG Qiu1*   

  1. 1.Department of Endocrinology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China
    2.Laboratory & Institute of Endocrinology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China
    3.Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei 230022,China
    *Corresponding author:ZHANG Qiu,Professor,Chief physician,Doctoral physician;E-mail:aynfmk@163.com
  • Published:2020-03-15 Online:2020-03-15

摘要: 背景 随着人们生活水平的提高及经济的发展,2型糖尿病(T2DM)及其慢性并发症发病率逐年增高,研究表明皮肤晚期糖基化终末产物(AGEs)与糖尿病血管病变关系密切,但在我国缺乏在社区中的大型筛查及研究。目的 研究经皮无创检测AGEs与T2DM血管性并发症的相关性及在社区筛查中的临床意义。方法 选取2017年8月—2018年5月与安徽医科大学第一附属医院签署医联体协议的2个社区卫生服务中心体检的30~75岁T2DM患者97例,其中44例T2DM未合并糖尿病并发症(单纯T2DM组),53例T2DM合并糖尿病并发症(T2DM伴并发症组),同时选取同期体检健康者272例作为对照组。分别测定受试者三酰甘油(TG)、总胆固醇(TC)、肌酐(Cr)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)及皮肤AGEs水平。测定踝肱指数(ABI)作为下肢血管病变评估标准,并将T2DM患者分为无周围血管病变、轻度周围血管病变、中度周围血管病变。测定尿白蛋白/肌酐比值(A/C比值),并将T2DM患者分为正常白蛋白尿、微量白蛋白尿、大量白蛋白尿。测定神经缺陷评分(NDS)作为周围神经病变指标,并将T2DM患者分为无周围神经病变、轻度周围神经病变、中度周围神经病变、重度周围神经病变。结果 三组皮肤AGEs水平比较,差异有统计学意义(P<0.05);其中单纯T2DM组和T2DM伴并发症组皮肤AGEs水平高于对照组;T2DM伴并发症组皮肤AGEs水平高于单纯T2DM组(P<0.05)。同一年龄段,T2DM伴并发症组皮肤AGEs水平高于单纯T2DM组(P<0.05)。随着T2DM伴周围血管病变、白蛋白尿、周围神经病变程度加重及T2DM并发症数目增多,皮肤AGEs水平均逐渐升高(P<0.05)。多因素Logistic回归分析结果显示,年龄〔OR=0.84,95%CI(0.73,0.97)〕和皮肤AGEs〔OR=1.35,95%CI(1.17,1.57)〕是T2DM伴周围血管病变发生的影响因素(P<0.05);性别〔OR=0.14,95%CI(0.03,0.61)〕、FBG〔OR=1.49,95%CI(1.10,2.02)〕、皮肤AGEs〔OR=1.09,95%CI(1.02,1.16)〕是T2DM伴白蛋白尿发生的影响因素(P<0.05);性别〔OR=0.23,95%CI(0.06,0.86)〕、HbA1c〔OR=1.68,95%CI(1.04,2.71)〕是T2DM伴周围神经病变发生的影响因素(P<0.05)。皮肤AGEs筛查T2DM并发症的受试者工作特征(ROC)曲线下面积(AUC)为0.833〔95%CI(0.753,0.914)〕,AGEs最佳切点值为71.5 AU,灵敏度为71.7%,特异度为86.4%。结论 皮肤AGEs检测可作为T2DM伴周围血管病变、肾脏病变的预测指标,为其用于社区T2DM伴并发症的无创筛查提供理论依据,但在皮肤AGEs与周围神经病变关系中需进一步研究证实。

关键词: 糖尿病, 2型;晚期糖基化终末产物;无创筛查;糖尿病并发症

Abstract: Background With the development of living conditions and economy,type 2 diabetes mellitus (T2DM) and T2DM-related chronic complications are increasing year by year.Studies show that advanced glycation end-products(AGEs) in skin are closely associated with diabetes-related vascular complications,but in China there is lack of use of AGEs in skin in large-scale community-based screening of T2DM.Objective To analyze the value of AGEs in skin measured noninvasively in community-based screening of T2DM-related vascular complications.Methods From 2 community health centers participating in the medical consortium led by the First Affiliated Hospital of Anhui Medical University after signing a agreement,369 individuals undergoing physical examination during August 2017 to May 2018 were recruited,including 44 with T2DM without complications (pure T2DM group),53 with T2DM and complications (T2DM with complications group),and 272 healthy controls(control group).Levels of TG,TC,Cr,FBG,HbA1c and AGEs in skin were measured in all participants.Prevalence of lower extremity vascular lesion was determined by ankle brachial index.By the prevalence and severity of peripheral vascular lesion,T2DM patients were stratified into T2DM without peripheral vascular lesion,T2DM with mild and moderate peripheral vascular lesion subgroups.By A/C ratio,T2DM patients were stratified into T2DM without albuminuria,T2DM with microalbuminuria,and macroalbuminuria subgroups.By Neurologic Deficit Score (NDS),T2DM patients were stratified into T2DM with normal neurological function,mild,moderate and severe neurologic deficit subgroups.Results There was significantly difference in skin AGEs among pure T2DM group,T2DM with complications group and control group (P<0.05).Specifically,the control group had lower AGEs in skin compared with other two groups (P<0.05).Compared with pure T2DM group,the level of AGEs in skin was higher in T2DM with complications group (P<0.05).T2DM patients with complications had higher level of AGEs than those without of the same age group (P<0.05).The level of skin AGEs increased with the number and severity of T2DM-related complications,such as peripheral vascular lesions,albuminuria,and peripheral neuropathy,and so on (P<0.05).Multivariate Logistic regression analysis showed that age 〔OR=0.84,95%CI(0.73,0.97)〕 and AGEs in skin〔OR=1.35,95%CI(1.17,1.57)〕 were associated with T2DM with peripheral vascular lesions (P<0.05).Gender 〔OR=0.14,95%CI(0.03,0.61)〕,FBG 〔OR=1.49,95%CI (1.10,2.02)〕 and AGEs in skin〔OR=1.09,95%CI (1.02,1.16)〕 were associated with T2DM with albuminuria (P<0.05).Gender 〔OR=0.23,95%CI (0.06,0.86)〕 and HbA1c 〔OR=1.68,95%CI (1.04,2.71)〕 were associated with T2DM with peripheral neuropathy (P<0.05).The AUC of AGEs in skin in identifying T2DM-related complications was 0.833〔95%CI(0.753,0.914)〕,the optimal cut-off point was 71.5 AU,the sensitivity of diagnosis was 71.7%,and the specificity was 86.4%.Conclusion AGEs in skin may be used as a predictor of T2DM with peripheral vascular disease and kidney disease,and may be used as a reference for noninvasive measurement of T2DM-related complications in the community.However,the relationship between AGEs in skin and diabetic neuropathy needs to be studied and verified further.

Key words: Diabetes mellitus, type 2;Advanced glycation end products;Noninvasive screening;Diabetes complications