Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy

Abstract

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.

Processed meat intake and incidence of Type 2 diabetes in younger and middle-aged women

“…The development of Type 2 diabetes was reduced by treatment with aminoguanidine, an AGE inhibitor, in genetically diabetic mice [48] and improvement of various features of insulin resistance was shown in mice fed a diet low in AGE [49]. In addition, a diet high in AGE was found to promote inflammatory mediators that might be important in the genesis of diabetes, such as vascular adhesion molecule-1, tumour necrosis factor-alpha, and C-reactive protein, in a study among 24 diabetic subjects [50]. AGE levels might be particularly high in those animal foods which are high in protein and fat [51] and which are processed [14].…”

Soft Drink Consumption Linked with Fatty Liver in the Absence of Traditional Risk Factors

“…Also, regarding obesity and aspartame, formaldehyde converted from the free methyl alcohol accumulates in the cells and damages mitochondrial DNA, with most toxicity effects occurring in the liver. Finally, the effect of caramel colourant has been incriminated as a cause of elevated liver enzymes and may be a potential source of advanced glycation end product, which may promote insulin resistance and can be proinflammatory (5,6,20). The extent to which fructose, aspartame and caramel contributed to severe fatty liver could not be concluded due to the small size of the cohort.…”

“…These factors include the consumption of fructose, aspartame, caramel (food colourant) and other covariants. These complexes of sugars and colourants may promote insulin resistance, lipid peroxidation and hepatic inflammation, and are a source of glycation end products (5,19,20). The extent to which excessive fructose, aspartame and caramel consumption might contribute to the high prevalence of liver disease in western societies and to the progression of NAFLD to NASH has not been investigated.…”

“…Recent evidence suggests that sugar-sweetened soft drink consumption is associated with the risk of obesity and diabetes because they contain large amounts of high-fructose corn syrup (HFCS), which raises blood glucose similarly to sucrose (4). In addition, soft drinks contain caramel colouring, which is rich in advanced glycation end products that might increase insulin resistance and inflammation (4)(5)(6).…”

Immunological detection of fructose-derived advanced glycation end-products

“…41 In human beings with diabetes, the mean concentration of C-reactive protein was 135% higher when the diet was high in AGEs than when cooking methods were altered to reduce the dietary AGEs content. 42 Even if the lactic acid bacteria beverage of 25 000 units is taken, concentration in the blood of Fru-AGE is B0.5 unit/ml (25 000 units  0.1/5000 ml). Therefore, the amount of Fru-AGE in the blood suggests that it was formed in situ.…”