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晚期糖基化终末产物积累的简单非侵入性评估

Simple non-invasive assessment of advanced glycation endproduct accumulation.

作者信息

Meerwaldt R, Graaff R, Oomen P H N, Links T P, Jager J J, Alderson N L, Thorpe S R, Baynes J W, Gans R O B, Smit A J

机构信息

Divisions of Vascular Medicine and Endocrinology, Department of Medicine U3.129, University Hospital Groningen, Hanzeplein, 9700 RB, Groningen, The Netherlands.

Department of Biomedical Engineering, University of Groningen, Groningen, The Netherlands.

出版信息

Diabetologia. 2004 Jul;47(7):1324-1330. doi: 10.1007/s00125-004-1451-2. Epub 2004 Jul 9.

Abstract

AIMS/HYPOTHESIS: The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects.

METHODS

Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL).

RESULTS

Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62, p</=0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were above the 95% CI of the mean value in control subjects, and correlated with age, diabetes duration, mean HbA(1)c of the previous year and creatinine levels.

CONCLUSIONS/INTERPRETATION: The AFR offers a simple alternative to invasive measurement of AGE accumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation.

摘要

目的/假设:晚期糖基化终末产物(AGE)的积累被认为在糖尿病慢性并发症和肾衰竭的发病机制中起作用。目前所有测量AGE积累的方法都需要进行侵入性采样。我们利用几种AGE具有自发荧光这一事实,开发了一种用于测量皮肤AGE积累的非侵入性工具——自发荧光读数器(AFR)。我们通过将使用AFR获得的值与糖尿病患者和对照受试者皮肤活检提取物中测量的AGE含量进行比较,验证了其用途。

方法

使用激发光源为300 - 420 nm的AFR,在46例1型和2型糖尿病患者以及46例年龄和性别匹配的对照受试者(大多数为白种人)的手臂和小腿测量皮肤荧光。自发荧光定义为整个发射光谱(420 - 600 nm)上每纳米的平均荧光与300 - 420 nm范围内每纳米的平均荧光之比。从手臂的同一部位获取皮肤活检样本,并分析其胶原交联荧光(CLF)和特定的AGE:戊糖苷、N-ε-(羧甲基)赖氨酸(CML)和N-ε-(羧乙基)赖氨酸(CEL)。

结果

自发荧光与CLF、戊糖苷、CML和CEL相关(r = 0.47 - 0.62,p≤0.002)。46例糖尿病患者中有32例(70%)的自发荧光值高于对照受试者平均值的95%置信区间,且与年龄、糖尿病病程、上一年的平均糖化血红蛋白(HbA1c)和肌酐水平相关。

结论/解读:AFR为AGE积累的侵入性测量提供了一种简单的替代方法,并且迄今为止已在非色素沉着皮肤中得到验证。AFR可能被证明是一种有用的临床工具,可用于快速评估糖尿病及其他与AGE积累相关疾病中与AGE相关的长期并发症风险。

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