Advanced Glycation Urinary Protein-Bound Biomarkers and Severity of Diabetic Nephropathy in Man

Advanced Glycation Urinary Protein-Bound Biomarkers and Severity of Diabetic Nephropathy in Man
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DOI:
10.1159/000331064
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发表时间:
2011-01-01
影响因子:
4.2
通讯作者:
Forbes, Josephine M.
Forbes, Josephine M.
中科院分区:
医学3区
文献类型:
--
作者:
Coughlan, Melinda T.;Patel, Sheila K.;Forbes, Josephine M.

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背景/目的:在糖尿病肾病患者中,晚期糖基化终末产物(AGEs)的形成加速。本研究的目的是确定尿中糖基化修饰蛋白的排泄是否可以作为1型或2型糖尿病患者白蛋白尿的生物标志物。研究方法:在三级转诊医院糖尿病门诊就诊的1型(n = 68)或2型(n = 216)社区糖尿病患者被归类为正常白蛋白尿(Normo,白蛋白排泄率(AER)= 200 μ g/min)。测定血清和尿液中AGE修饰蛋白。结果如下:在1型糖尿病和2型糖尿病患者中,蛋白尿的程度与尿中AGE修饰蛋白之间存在明显的相关性(p < 0.0001)。排除1型糖尿病患者,尿中AGE羧甲基赖氨酸排泄与AER相关,而2型糖尿病和大量白蛋白尿患者尿中甲基乙二醛(AGE中间体)增加。这些变化是独立的同位素肾小球滤过率水平。AGEs或AGEs可溶性受体的血清浓度与1型或2型糖尿病的蛋白尿并不一致。结论:尿中AGEs修饰的蛋白质排泄可能是1型和2型糖尿病患者白蛋白尿的有用生物标志物,有助于在更大的糖尿病队列中进行前瞻性研究。版权所有(C)2011 S. Karger AG,巴塞尔
Background/Aims: The formation of advanced glycation end products (AGEs) is accelerated in patients with diabetic nephropathy. The aim of this study was to ascertain if the urinary excretion of proteins modified by advanced glycation can be used as biomarkers for albuminuria in individuals with type 1 or type 2 diabetes. Methods: Community-based patients with type 1 (n = 68) or type 2 diabetes (n = 216) attending a diabetes clinic of a tertiary referral hospital were classified as having normoalbuminuria (Normo, albumin excretion rate (AER) = 200 mu g/min). Serum and urine AGE-modified proteins were measured. Results: In patients with both type 1 diabetes and type 2 diabetes, there was a clear association between the degree of albuminuria and urinary AGE-modified proteins (p < 0.0001). Exclusive to patients with type 1 diabetes, urinary excretion of the AGE carboxymethyllysine correlated with AER, whereas patients with type 2 diabetes and macroalbuminuria had an increase in urinary methylglyoxal, an AGE intermediate. These changes were independent of isotopic glomerular filtration rate levels. Serum concentrations of AGEs or soluble receptor for AGEs were not consistently associated with albuminuria in either type 1 or type 2 diabetes. Conclusions: Urinary excretion of proteins modified by AGEs may be useful biomarkers of albuminuria in individuals with type 1 and type 2 diabetes, warranting prospective investigation in larger diabetic cohorts. Copyright (C) 2011 S. Karger AG, Basel