Diabetic threesome (hyperglycaemia, renal function and nutrition) and advanced glycation end products: evidence for the multiple-hit agent?

Abstract

Complex chemical processes termed non-enzymic glycation that operate in vivo and similar chemical interactions between sugars and proteins that occur during thermal processing of food (known as the Maillard reaction) are one of the interesting examples of a potentially-harmful interaction between nutrition and disease. Non-enzymic glycation comprises a series of reactions between sugars, a-oxoaldehydes and other sugar derivatives and amino groups of amino acids, peptides and proteins leading to the formation of heterogeneous moieties collectively termed advanced glycation end products (AGE). AGE possess a wide range of chemical and biological properties and play a role in diabetes-related pathology as well as in several other diseases. Diabetes is, nevertheless, of particular interest for several reasons: (1) chronic hyperglycaemia provides the substrates for extracellular glycation as well as intracellular glycation; (2) hyperglycaemia-induced oxidative stress accelerates AGE formation in the process of glycoxidation; (3) AGE-modified proteins are subject to rapid intracellular proteolytic degradation releasing free AGE adducts into the circulation where they can bind to several pro-inflammatory receptors, especially receptor of AGE; (4) kidneys, which are principally involved in the excretion of free AGE adducts, might be damaged by diabetic nephropathy, which further enhances AGE toxicity because of diminished AGE clearance. Increased dietary intake of AGE in highly-processed foods may represent an additional exogenous metabolic burden in addition to AGE already present endogenously in subjects with diabetes. Finally, inter-individual genetic and functional variability in genes encoding enzymes and receptors involved in either the formation or the degradation of AGE could have important pathogenic, nutrigenomic and nutrigenetic consequences. Advanced glycation end products: Diabetes mellitus: Diabetic nephropathy: NutrigeneticsDiabetes mellitus is the most common metabolic disease. Its prevalence is steadily rising (with few exceptions) globally, having already reached epidemic proportions in industrialised countries. Current WHO estimates predict that the number of individuals with diabetes will reach approximately 300 million by 2025 (1) . The diabetes mellitus epidemic is paralleled by body-weight changes (overweight or obesity), and in both cases there is a clear-cut correlation; the faster the socio-economic progress (and subsequent lifestyle changes) in a given society the steeper the rise in the incidence and prevalence of diabetes mellitus and obesity. Both common types of diabetes mellitus, type 1 (T1DM) and type 2 (T2DM), are ethiopathogenetically 'complex' diseases with a certain extent of genetic predisposition and a substantial influence of environmental factors (particularly diet and physical (in)activity), although the phenotypic complexity and prevalence of T2DM is much higher. Since diabetes mellitus is characterised by profound abnormalities in energysubstrate partitioning as a result of def...

Dietary glycotoxins induce RAGE and VEGF up-regulation in the retina of normal rats

“…Circulating AGEs and fructosamine levels, a major source of AGEs in vivo (Kankova, 2008), were increased in both young and adult animals exposed to high-AGE diet compared to low AGE, reflecting the increased absorption of dietary AGEs and reduced renal clearance. Moreover, peripheral AGE levels were correlated with increased AGE deposition in retina and uveal layer and specifically in RPE supporting the view that circulating AGEs cross both the outer and the inner blood brain barrier and reach the inner layers of the retina (Shimizu et al, 2011(Shimizu et al, , 2013.…”

Involvement of Advanced Glycation End Products in the Pathogenesis of Diabetic Retinopathy

“…Moreover, apart from endogenous formation of AGEs, they can also be generated from exogenous sources including tobacco, smoke, and diet [12]. Foodprocessing methods, such as prolonged heat processing and microwave cooking, can also accelerate the generation of glyco-oxidation and lipo-oxidation adducts, thus increasing the proportion of AGEs ingestion along with food [12,13].…”

Red Meat Intake and the Risk of Cardiovascular Disease

“…Through its effect on systolic blood pressure, the high sodium content of processed red meat may also contribute to CVD risk [9,10]. Compounds created by cooking red meat, including heterocyclic amines and advanced glycation end-products, may also be linked with CHD [26][27][28][29][30][31][32][33]. When major sources of protein, such as nuts and fish, are used to replace red meat in the diet, saturated fat and heme iron and sodium decrease, while intake of polyunsaturated fat increases.…”