Vlassara Helen, Cai Weijing, Crandall Jill, Goldberg Teresia, Oberstein Robert, Dardaine Veronique, Peppa Melpomeni, Rayfield Elliot J
Division of Experimental Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15596-601. doi: 10.1073/pnas.242407999. Epub 2002 Nov 12.
Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-alphabeta-actin mRNA ratio was 1.4 +/- 0.5 on H-AGE and 0.9 +/- 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 +/- 429 and 698 +/- 347 ngml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-alpha rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.
饮食是促炎晚期糖基化终产物（热生成的晚期糖基化终产物）的主要环境来源；其对人类的影响尚不清楚。我们探讨了两种等量饮食的作用，一种是常规饮食（高晚期糖基化终产物，H-AGE），另一种晚期糖基化终产物含量低5倍（L-AGE），对24名糖尿病受试者炎症介质的影响：11名受试者进行为期2周的交叉试验，13名受试者进行为期6周的研究。在食用H-AGE饮食2周后，血清晚期糖基化终产物增加了64.5%（P = 0.02），而食用L-AGE饮食后则下降了30%（P = 0.02）。单核细胞肿瘤坏死因子-α/β-肌动蛋白mRNA比值在H-AGE饮食时为1.4±0.5，在L-AGE饮食时为0.9±0.5（P = 0.05），而血清血管黏附分子-1在L-AGE饮食和H-AGE饮食时分别为698±347和1,108±429 ng/ml（P = 0.01）。6周后，外周血单核细胞肿瘤坏死因子-α在H-AGE饮食时上升了86.3%（P = 0.006），在L-AGE饮食时下降了20%（P，无显著性差异）；C反应蛋白在H-AGE饮食时增加了35%，在L-AGE饮食时下降了20%（P = 0.014），血管黏附分子-1在L-AGE饮食时下降了20%（P < 0.01），在H-AGE饮食时增加了4%。血清晚期糖基化终产物在H-AGE饮食时增加了28.2%（P = 0.06），在L-AGE饮食时减少了40%（P = 0.02），而晚期糖基化终产物修饰的低密度脂蛋白在H-AGE饮食时增加了32%，在L-AGE饮食时减少了33%（P < 0.05）。因此，在糖尿病中，环境（饮食中的）晚期糖基化终产物会促进炎症介质的产生，导致组织损伤。限制饮食中的晚期糖基化终产物可抑制这些作用。
