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.

AGEs accumulate at a faster-than-normal rate in arteries and the circulation of patients with diabetes; the increase in circulating AGE peptides parallels the severity of renal functional impairment in diabetic nephropathy.

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In the thrombolytic era, mortality rates of diabetic patients who have had acute myocardial infarction remain 1.5 to 2 times higher than those in nondiabetic patients. This increased mortality rate is caused by diverse mechanisms that affect myocardial function and blood supply and by the tendency toward thrombosis in diabetic patients. Current therapies for myocardial infarction are effective in these patients. Improved metabolic control may also decrease mortality rates.