Yanagisawa K, Makita Z, Shiroshita K, Ueda T, Fusegawa T, Kuwajima S, Takeuchi M, Koike T
Second Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Metabolism. 1998 Nov;47(11):1348-53. doi: 10.1016/s0026-0495(98)90303-1.
Late rearrangement products that accumulate by glycation of proteins, known as advanced glycation end products (AGEs), have been implicated in the pathogenesis of complications related to diabetes. Circulating AGEs, especially in the form of a small peptide (AGE-peptide) of less than 10 kd, increase in the blood of diabetic patients with end-stage renal disease (ESRD). The aim of the study was to evaluate AGE-peptide levels by measuring AGE-specific fluorescence (excitation at 370 nm and emission at 440 nm) and to examine the relationship between AGE-peptide and diabetic nephropathy. AGE-specific fluorescence in serum and urine were examined in diabetic subjects with various levels of renal complications of varying severity: normoalbuminuria (N), microalbuminuria (Mi), macroalbuminuria (Ma), chronic renal failure (C), and hemodialysis (HD). We also assessed correlations among the AGE-peptide level and age, duration of diabetes, hemoglobin A1c (HbA1c), serum creatinine, and creatinine clearance. Serum and urine AGE-peptide levels in C and HD were significantly higher than in N, Mi, and Ma. Serum AGE-peptide levels were significantly correlated with serum creatinine (r=.866, P < .0001) and creatinine clearance (r=-.720, P < .0001) but not with duration of diabetes or age. There was a significant correlation between AGE-peptide levels measured by enzyme-linked immunosorbent assay (ELISA) and levels determined from the specific fluorescence intensity (r=.688, P < .0001). These findings suggest that renal function may play a greater role in the accumulation of AGEs than persistent hyperglycemia in diabetic patients. Measurement of AGE-specific fluorescence (ie, AGE-peptide) may serve as a simple and useful test to assess circulating AGE levels and monitor AGE excretion.
蛋白质糖基化积累产生的晚期重排产物，即晚期糖基化终末产物（AGEs），与糖尿病相关并发症的发病机制有关。循环中的AGEs，尤其是小于10kd的小肽形式（AGE-肽），在终末期肾病（ESRD）糖尿病患者的血液中会增加。本研究的目的是通过测量AGE特异性荧光（激发波长370nm，发射波长440nm）来评估AGE-肽水平，并研究AGE-肽与糖尿病肾病之间的关系。在患有不同严重程度肾脏并发症的糖尿病患者中检测血清和尿液中的AGE特异性荧光：正常白蛋白尿（N）、微量白蛋白尿（Mi）、大量白蛋白尿（Ma）、慢性肾衰竭（C）和血液透析（HD）。我们还评估了AGE-肽水平与年龄、糖尿病病程、糖化血红蛋白（HbA1c）、血清肌酐和肌酐清除率之间的相关性。C组和HD组的血清和尿液AGE-肽水平显著高于N组、Mi组和Ma组。血清AGE-肽水平与血清肌酐显著相关（r = 0.866，P < 0.0001）和肌酐清除率显著相关（r = -0.720，P < 0.0001），但与糖尿病病程或年龄无关。通过酶联免疫吸附测定（ELISA）测量的AGE-肽水平与由特异性荧光强度测定的水平之间存在显著相关性（r = 0.688，P < 0.0001）。这些发现表明，在糖尿病患者中，肾功能在AGEs积累中可能比持续性高血糖起更大作用。测量AGE特异性荧光（即AGE-肽）可作为评估循环AGE水平和监测AGE排泄的简单有用的检测方法。
