Journal Article

Inflammatory Mediators Are Induced by Dietary Glycotoxins, a Major Risk Factor for Diabetic Angiopathy

Vlassara, Helen, Oberstein, Robert, Cai, Weijing, Crandall, Jill, Goldberg, Teresia, Dardaine, Veronique, Peppa, Melpomeni, Rayfield, Elliot J.

2002

Overview

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-α/β-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 ng/ml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-α 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: administration & dosage / adverse effects / analogs & derivatives / analysis / Biological Sciences / Biomarkers / blood / breads / C-reactive protein / C-Reactive Protein - analysis / chicken meat / Cholesterols / Cross-Over Studies / Diabetes / Diabetes Complications / Diabetes Mellitus / Diabetes Mellitus - metabolism / Diabetic Angiopathies / Diabetic Angiopathies - epidemiology / Diabetic Angiopathies - etiology / Diabetic diets / Diet / Diet - adverse effects / diet therapy / Dietary Carbohydrates / Dietary Carbohydrates - administration & dosage / Dietary Carbohydrates - adverse effects / Dietary Fats / Dietary Fats - administration & dosage / Dietary Fats - adverse effects / Dietary Proteins / Dietary Proteins - administration & dosage / Dietary Proteins - adverse effects / drug effects / egg yolk / epidemiology / etiology / Fasting / Female / Food / Food Analysis / food intake / Food, Formulated / Gene Expression Regulation / Gene Expression Regulation - drug effects / Glycation End Products, Advanced - administration & dosage / Glycation End Products, Advanced - adverse effects / Glycation End Products, Advanced - blood / Glycosylation End Products, Advanced / Humans / inflammation / Inflammation Mediators / Inflammation Mediators - metabolism / Lipid Peroxidation / Lipids / Lysine / Lysine - adverse effects / Lysine - analogs & derivatives / Lysine - analysis / Male / metabolism / Middle Aged / Molecules / pasta / Pyruvaldehyde / Pyruvaldehyde - adverse effects / Pyruvaldehyde - analysis / Risk Factors / toxic substances / Tumor Necrosis Factor-alpha / Tumor Necrosis Factor-alpha - analysis / tumor necrosis factors / tuna / Vascular Cell Adhesion Molecule-1 / Vascular Cell Adhesion Molecule-1 - analysis / vascular diseases