High Levels of Dietary Advanced Glycation End Products Transform Low-Dersity Lipoprotein Into a Potent Redox-Sensitive Mitogen-Activated Protein Kinase Stimulant in Diabetic Patients

Abstract

Background-LDL modification by endogenous advanced glycation end products (AGEs) is thought to contribute to cardiovascular disease of diabetes. It remains unclear, however, whether exogenous (diet-derived) AGEs influence glycoxidation and endothelial cell toxicity of diabetic LDL. Methods and Results-Twenty-four diabetic subjects were randomized to either a standard diet (here called high-AGE, HAGE) or a diet 5-fold lower in AGE (LAGE diet) for 6 weeks. LDL pooled from patients on HAGE diet (Db-HAGE-LDL) was more glycated than LDL from the LAGE diet group (

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

“…Circulating AGEs may arise from intracellular reactive glucose metabolites [33] or they can be formed in the circulation [34]. Recent studies suggest that the diet could be a source of AGEs [35]. However, in the present study, all participants were fasting.…”

“…Further studies, including therapeutic studies with AGE-lowering compounds, are needed to substantiate this conclusion. In short-term studies, a decrease in dietary AGEs has been shown to reduce levels of inflammatory mediators such as peripheral blood mononuclear cell TNF-α and hs-CRP [39], as well as glycoxidised LDL [35]. It has been shown that hs-CRP is an independent risk factor for CHD mortality not only in non-diabetic individuals [40], but also in patients with type 2 diabetes [41].…”

Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties

“…High plasma concentrations of AGE have been associated with increased rates of CAD [34] as well as kidney damage [35]. AGE modifications have also been reported to cause changes in lipoprotein metabolism affecting properties of LDL particles [36], expression of lipoprotein lipase [37] and the functionality of scavenger receptors, including SR-B1 [38]. Most of these effects were related to common AGE moieties, such as CML [39], and not related to a specific protein.…”

Trends in the Evaluation of Lipid Peroxidation Processes

“…All these structural and functional changes have direct clinical consequences, leading to the acceleration of the general aging process, but also to some pathological phenomena, associated with the increase of the capillary permeability, impairment of the blood cell function, etc. ROS lesions are frequently associated with aging [Dröge & Schipper, 2007;Griffiths et al, 2011], atheroclerosis [Hulsmans & Holvoet, 2010], cardio-vascular disease [Dikalov & Nazarewicz, 2012;Puddu et al, 2009], type I or type II diabetes mellitus [Cai et al, 2004], autoimmune disorders, neurodegenerative disorders such as Parkinson [Yoritaka et al, 1996] or Alzheimer's disease [Sayre et al, 1997;Takeda et al, 2000], inflammatory diseases such as reumatoid arthritis [Griffiths et al, 2011] or different types of cancers [Lenaz, 2012;Li et al, 2009;Manda et al, 2009].…”