Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy.
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.
Vlassara
Helen
H
Division of Experimental Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, NY 10029, USA. helen.vlassara@mssm.edu
Cai
Weijing
W
Crandall
Jill
J
Goldberg
Teresia
T
Oberstein
Robert
R
Dardaine
Veronique
V
Peppa
Melpomeni
M
Rayfield
Elliot J
EJ
D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D018592:Cross-Over Studies; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000209:etiology*; D004032:Diet / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004044:Dietary Proteins / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005504:Food Analysis; D005526:Food, Formulated; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015227:Lipid Peroxidation; D008239:Lysine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011765:Pyruvaldehyde / Q000009:adverse effects / Q000032:analysis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D015415:Biomarkers; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C048496:N(6)-carboxymethyllysine; D011765:Pyruvaldehyde; D002097:C-Reactive Protein; D008239:Lysine