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Habitual intake of dietary advanced glycation end products is not associated with generalized microvascular function-the Maastricht Study.
Linkens, AMA, Houben, AJHM, Kroon, AA, Schram, MT, Berendschot, TTJM, Webers, CAB, van Greevenbroek, M, Henry, RMA, de Galan, B, Stehouwer, CDA, et al
The American journal of clinical nutrition. 2022;(2):444-455
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Abstract
BACKGROUND Endogenously formed advanced glycation end products (AGEs) may be important drivers of microvascular dysfunction and the microvascular complications of diabetes. AGEs are also formed in food products, especially during preparation methods involving dry heat. OBJECTIVES We aimed to assess cross-sectional associations between dietary AGE intake and generalized microvascular function in a population-based cohort. METHODS In 3144 participants of the Maastricht Study (mean ± SD age: 60 ± 8 y, 51% men) the dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of our ultra-performance LC-tandem MS dietary AGE database and an FFQ. Microvascular function was determined in the retina as flicker light-induced arteriolar and venular dilation and as central retinal arteriolar and venular equivalents, in plasma as a z score of endothelial dysfunction biomarkers (soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1, soluble E-selectin, and von Willebrand factor), in skin as the heat-induced skin hyperemic response, and in urine as 24-h albuminuria. Associations were evaluated using multiple linear regression adjusting for demographic, cardiovascular, lifestyle, and dietary factors. RESULTS Overall, intakes of CML, CEL, and MG-H1 were not associated with the microvascular outcomes. Although higher intake of CEL was associated with higher flicker light-induced venular dilation (β percentage change over baseline: 0.14; 95% CI: 0.02, 0.26) and lower plasma biomarker z score (β: -0.04 SD; 95% CI: -0.08, -0.00 SD), the effect sizes were small and their biological relevance can be questioned. CONCLUSIONS We did not show any strong association between habitual intake of dietary AGEs and generalized microvascular function. The contribution of dietary AGEs to generalized microvascular function should be further assessed in randomized controlled trials using specifically designed dietary interventions.
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Advanced Glycation End Products: A Sweet Flavor That Embitters Cardiovascular Disease.
Pinto, RS, Minanni, CA, de Araújo Lira, AL, Passarelli, M
International journal of molecular sciences. 2022;(5)
Abstract
Epidemiological studies demonstrate the role of early and intensive glycemic control in the prevention of micro and macrovascular disease in both type 1 and type 2 diabetes mellitus (DM). Hyperglycemia elicits several pathways related to the etiopathogenesis of cardiovascular disease (CVD), including the generation of advanced glycation end products (AGEs). In this review, we revisit the role played by AGEs in CVD based in clinical trials and experimental evidence. Mechanistic aspects concerning the recognition of AGEs by the advanced glycosylation end product-specific receptor (AGER) and its counterpart, the dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST) and soluble AGER are discussed. A special focus is offered to the AGE-elicited pathways that promote cholesterol accumulation in the arterial wall by enhanced oxidative stress, inflammation, endoplasmic reticulum stress and impairment in the reverse cholesterol transport (RCT).
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Metabolic transit of dietary advanced glycation end-products - the case of NƐ-carboxymethyllysine.
Tessier, FJ, Boulanger, E, Howsam, M
Glycoconjugate journal. 2021;(3):311-317
Abstract
The Maillard reaction, also called glycation, is one of the major chemical reactions responsible for most yellow-to-brown colors and aromas in cooked foods. This reaction between reducing sugars and amino functions on proteins affects not only the flavor of food, but also leads to the formation of an heterogenous group of structurally-modified amino acids. Some of these, known as "advanced glycation end products" (AGEs), have been found in both foods and human biological fluids, tissues and organs. Except for those that are formed over long periods in vivo at 37 °C, AGEs in the body originate from the digestion and absorption of dietary sources. A high or chronic exposure to dietary AGEs (dAGEs) is suspected as potentially detrimental to human health and studies in the field of food safety have begun to focus their attention on the metabolic transit of dAGEs. This review presents some important findings in this field, with a focus on NƐ-carboxymethyllysine, and presents the evidence for and against an association between intake of dAGEs and their presence in the body. New and promising avenues of research are described, and some future directions outlined.
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Correlation between hyperglycemia and glycated albumin with retinopathy of prematurity.
Almeida, AC, Silva, GA, Santini, G, Brízido, M, Correia, M, Coelho, C, Borrego, LM
Scientific reports. 2021;(1):22321
Abstract
To determine the association between hyperglycemia, glycated albumin (GlyA) and retinopathy of prematurity (ROP). Prospective study of all infants under ROP screening from March 2017 to July 2019. All demographic, clinical and laboratory data were collected. Glucose was measured at birth and every 8 h for the first week and serum GlyA was evaluated at birth, 1st, 2nd and 4th weeks after birth. Reference range for GlyA was obtained. Univariate logistic regression was used to examine risk factors for ROP followed by multivariate regression. A total of 152 infants were included in the study. Median gestational age was 30 weeks and median birth weight 1240 g. Thirty-three infants (21.7%) had ROP. Hyperglycemia was present in 24 (72.7%) infants diagnosed with any ROP versus 6 (0.05%) in those without ROP. Median GlyA at birth, 1st, 2nd and 4th and respective reference ranges were 8.50% (6.00-12.65), 8.20% (5.32-11.67), 8.00% (5.32-10.00) and 7.90% (5.30-9.00) respectively. After multivariate logistic regression, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors (Exp (B) 28.062, 95% CI for Exp(B) 7.881-99.924 p < 0.001). In our cohort, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors.
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Dietary AGEs as Exogenous Boosters of Inflammation.
Garay-Sevilla, ME, Rojas, A, Portero-Otin, M, Uribarri, J
Nutrients. 2021;(8)
Abstract
Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated).
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Advanced glycation end products and their receptors in serum of patients with type 2 diabetes.
Indyk, D, Bronowicka-Szydełko, A, Gamian, A, Kuzan, A
Scientific reports. 2021;(1):13264
Abstract
Glycation is a non-enzymatic process involving the reaction of reducing sugars or reactive oxoaldehyde with proteins, lipids or nucleic acids, which results in the formation of advanced glycation end products (AGEs). The presented work discusses the glycation process in people with advanced stage of type 1 or type 2 diabetes. The concentration of different AGEs and their receptors for 58 serum samples was determined by ELISA and by spectrofluorimetric methods. In addition to fluorescent low molecular weight and protein-bound AGEs, we have also marked a new class of AGEs: melibiose-derived glycation product (MAGE). Our attention was also focused on the two groups of AGEs receptors: scavenger receptors (SR-A and SR-B) and RAGE. The correlation between the SR-AI scavenging receptors concentration and the fluorescence of AGEs as well as diabetes biological markers: GFR, creatinine contentration and HbA1c was demonstrated. A relationship between the concentration of AGEs and their receptors was also found in serum sample of patients treated with the metformin and aspirin. Furthermore, the concentration of SR-AI scavenger and the fluorescence of total AGEs was significantly lower in treated patients than in non treated patients. AGEs have also been found to contribute to the development of cardiovascular disease, atherosclerosis and diabetic complications, what could be deduced from the correlation of AGEs level and HDL cholesterol or uric acid level. Thus, it was confirmed that AGEs are involved in the pathomechanism of diabetes and other degenerative diseases. Nowadays, it is believed that AGEs due to the long time remaining in the body may be an important diagnostic marker. Their determination may allow monitoring the progression of the disease and the effectiveness of the therapy.
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Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer's Disease.
Aaseth, J, Skalny, AV, Roos, PM, Alexander, J, Aschner, M, Tinkov, AA
International journal of molecular sciences. 2021;(17)
Abstract
The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer's disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.
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Effects of an equol-containing supplement on advanced glycation end products, visceral fat and climacteric symptoms in postmenopausal women: A randomized controlled trial.
Yoshikata, R, Myint, KZY, Ohta, H, Ishigaki, Y
PloS one. 2021;(9):e0257332
Abstract
INTRODUCTION Equol, an isoflavone derivative whose chemical structure is similar to estrogen, is considered a potentially effective agent for relieving climacteric symptoms, for the prevention of lifestyle-related diseases, and for aging care in postmenopausal women. We investigated the effect of an equol-containing supplement on metabolism and aging and climacteric symptoms with respect to internally produced equol in postmenopausal women. METHODS A single-center, randomized controlled trial (registration number: UMIN000030975) on 57 postmenopausal Japanese women (mean age: 56±5.37 years) was conducted. Twenty-seven women received the equol supplement, while the remaining received control. Metabolic and aging-related biomarkers were compared before and after the 3-month intervention. Climacteric symptoms were assessed every month using a validated self-administered questionnaire in Japanese postmenopausal women. RESULTS Three months post-intervention, the treatment group showed significant improvement in climacteric symptoms compared to the control group (81% vs. 53%, respectively, p = 0.045). We did not observe any beneficial effect on metabolic and aging-related biomarkers in the intervention group. However, in certain populations, significant improvement in skin autofluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. CONCLUSION Women receiving equol supplementation showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously produced equol to improve skin aging and visceral fat in certain populations.
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The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction.
Sergi, D, Boulestin, H, Campbell, FM, Williams, LM
Molecular nutrition & food research. 2021;(1):e1900934
Abstract
Advanced glycation end products (AGEs) are a heterogeneous group of molecules produced, non-enzymatically, from the interaction between reducing sugars and the free amino groups of proteins, nucleic acids, and lipids. AGEs are formed as a normal consequence of metabolism but can also be absorbed from the diet. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes, and kidneys. Increased levels of AGEs are also detrimental to metabolic health and may contribute to the metabolic abnormalities induced by the Western diet, which is high in processed foods and represents a significant source of AGEs. While increased AGE levels are a consequence of diabetic hyperglycaemia, AGEs themselves activate signaling pathways, which compromise insulin signaling and pancreatic β-cell function, thus, contributing to the development of type 2 diabetes mellitus (T2DM). Furthermore, AGEs may also contribute to the obesogenic effects of the Western diet by promoting hypothalamic inflammation and disrupting the central control of energy balance. Here, the role of dietary AGEs in metabolic dysfunction is reviewed with a focus on the mechanisms underpinning their detrimental role in insulin resistance, pancreatic β-cell dysfunction, hypothalamic control of energy balance, and the pathogenesis of T2DM and obesity.
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The Effects of Taurine Supplementation on Metabolic Profiles, Pentosidine, Soluble Receptor of Advanced Glycation End Products and Methylglyoxal in Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.
Esmaeili, F, Maleki, V, Kheirouri, S, Alizadeh, M
Canadian journal of diabetes. 2021;(1):39-46
Abstract
OBJECTIVES Advanced glycation end products, along with methylglyoxal (MGO) as their precursor, play a major role in increased complications of type 2 diabetes mellitus (T2DM). Taurine (2-aminoethanesulphonic acid), a conditionally essential amino acid, is found in most mammalian tissues. Taurine is known as an antiglycation compound. This study was designed to investigate the effects of taurine supplementation on metabolic profiles, pentosidine, MGO and soluble receptors for advanced glycation end products in patients with T2DM. METHODS In this double-blind randomized controlled trial, 46 patients with T2DM were randomly allocated into taurine and placebo groups. Participants received either 3,000 mg/day taurine or placebo for 8 weeks. Metabolic profiles, pentosidine, MGO and soluble receptors for advanced glycation end products levels were assessed after 12 h of fasting at baseline and completion of the clinical trial. Independent t test, paired t test, Pearson correlation and analysis of covariance were used for analysis. RESULTS The mean serum levels of fasting blood sugar (p=0.01), glycated hemoglobin (p=0.04), insulin (p=0.03), homeostasis model assessment-insulin resistance (p=0.004), total cholesterol (p=0.01) and low-density lipoprotein cholesterol (p=0.03) significantly were reduced in the taurine group at completion compared with the placebo group. In addition, after completion of the study, pentosidine (p=0.004) and MGO (p=0.006) were significantly reduced in the taurine group compared with the placebo group. CONCLUSIONS The results of this trial show that taurine supplementation may decrease diabetes complications through improving glycemic control and advanced glycation end products.