Blood and Tissue Advanced Glycation End Products as Determinants of Cardiometabolic Disorders Focusing on Human Studies

Abstract

Cardiometabolic disorders are characterised by a cluster of interactive risk determinants such as increases in blood glucose, lipids and body weight, as well as elevated inflammation and oxidative stress and gut microbiome changes. These disorders are associated with onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). T2DM is strongly associated with CVD. Dietary advanced glycation end products (dAGEs) attributable from modern diets high in sugar and/or fat, highly processed foods and high heat-treated foods can contribute to metabolic etiologies of cardiometabolic disorders. This mini review aims to determine whether blood dAGEs levels and tissue dAGEs levels are determinants of the prevalence of cardiometabolic disorders through recent human studies. ELISA (enzyme-linked immunosorbent assay), high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) for blood dAGEs measurement and skin auto fluorescence (SAF) for skin AGEs measurement can be used. Recent human studies support that a diet high in AGEs can negatively influence glucose control, body weight, blood lipid levels and vascular health through the elevated oxidative stress, inflammation, blood pressure and endothelial dysfunction compared with a diet low in AGEs. Limited human studies suggested a diet high in AGEs could negatively alter gut microbiota. SAF could be considered as one of the predictors affecting risks for cardiometabolic disorders. More intervention studies are needed to determine how dAGEs are associated with the prevalence of cardiometabolic disorders through gut microbiota changes. Further human studies are conducted to find the association between CVD events, CVD mortality and total mortality through SAF measurement, and a consensus on whether tissue dAGEs act as a predictor of CVD is required.

Liquid Chromatography with Tandem Mass Spectrometry Analysis of Carboxymethyl Lysine in Indonesian Foods

“…Carboxymethyl lysine is one of several advanced glycation end products (AGEs) that is mostly used to measure the AGE content in foods or in the body [ 1 , 2 , 3 , 4 , 5 ] because of its stability and irreversible structure [ 6 , 7 ]. AGEs also known as glycotoxins, are harmful compounds [ 8 , 9 ] that are formed through nonenzymatic reactions between reducing sugars and foods, resulting in a brownish coloration that was first mentioned by Louis Camille Maillard in 1912 [ 10 ].…”

“…Circulatory AGEs in the body are associated with the balance of exogenous AGEs from dietary and cigarette smoke, the accumulation of AGEs in the body, endogenous AGEs synthesis, and the clearance of AGEs [ 7 , 14 ]. A correlation between high AGE consumption and circulatory CML was seen in several studies [ 15 , 16 , 17 , 18 , 19 ]; AGE is furthermore believed to be associated with insulin resistance [ 7 , 20 ], obesity [ 21 , 22 ], cardiovascular disease, and renal failure [ 1 , 7 , 23 , 24 , 25 ].…”

Advanced Glycation End Products Upregulate CD40 in Human Retinal Endothelial and Müller Cells: Relevance to Diabetic Retinopathy

“…Advanced glycation end products (AGEs) accumulate in tissues in diabetic patients and are linked to the development of complications of this disease [ 8 , 9 ]. AGEs are formed on amino groups (mainly those of lysine and arginine) of proteins via a multistep process of non-enzymatic glycosylation initiated by reducing sugars [ 9 ]. The reactive dicarbonyl intermediate methylglyoxal (MGO) is an important precursor of AGEs [ 8 , 10 ].…”

A Citrus and Pomegranate Complex Reduces Methylglyoxal in Healthy Elderly Subjects: Secondary Analysis of a Double-Blind Randomized Cross-Over Clinical Trial

“…Moreover, AGEs accumulate in the extracellular space in tissues and organs. Their role in the development of cardiometabolic and neurodegenerative diseases has been demonstrated in numerous studies [12][13][14][15]. The glyoxalase system, comprising glyoxalase I (Glo1) and glyoxalase II (Glo2), primarily detoxifies MGO in the human body, maintaining relatively low intracellular MGO levels under normal physiological conditions [16,17].…”