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Dietary Advanced Glycation End-products (AGE) and Risk of Breast Cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO).
Omofuma, OO, Turner, DP, Peterson, LL, Merchant, AT, Zhang, J, Steck, SE
Cancer prevention research (Philadelphia, Pa.). 2020;(7):601-610
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Abstract
Advanced glycation end-products (AGEs) are implicated in the pathogenesis of several chronic diseases including cancer. AGEs are produced endogenously but can also be consumed from foods. AGE formation in food is accelerated during cooking at high temperatures. Certain high fat or highly processed foods have high AGE values. The objective of the study was to assign and quantify Nϵ-carboxymethyl-lysine (CML)-AGE content in food and investigate the association between dietary AGE intake and breast cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The study included women enrolled in the intervention arm who were cancer-free at baseline and completed a baseline questionnaire and food frequency questionnaire (DQX). CML-AGE values were assigned and quantified to foods in the DQX using a published AGE database. Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer among all women, and stratified by race/ethnicity, invasiveness of disease, and hormone receptor status. After a median 11.5 years of follow-up, 1,592 women were diagnosed with breast cancer. Higher CML-AGE intake was associated with increased risk of breast cancer among all women (HRQ5VSQ1, 1.30; 95% CI, 1.04-1.62; P trend = 0.04) and in non-Hispanic white women (HRT3VST1, 1.21; 95% CI, 1.02-1.44). Increased CML-AGE intake was associated with increased risk of in situ (HRT3VST1, 1.49; 95% CI, 1.11-2.01) and hormone receptor-positive (HRT3VST1, 1.24; 95% CI, 1.01-1.53) breast cancers. In conclusion, high intake of dietary AGE may contribute to increased breast cancer.
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Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study.
Martens, RJH, Broers, NJH, Canaud, B, Christiaans, MHL, Cornelis, T, Gauly, A, Hermans, MMH, Konings, CJAM, van der Sande, FM, Scheijen, JLJM, et al
PloS one. 2019;(8):e0221058
Abstract
BACKGROUND Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. METHODS We examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N∈-(carboxymethyl)lysine (CML), N∈-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. RESULTS After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. CONCLUSIONS In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.
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Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients.
Torino, C, Pizzini, P, Cutrupi, S, Tripepi, R, Vilasi, A, Tripepi, G, Mallamaci, F, Zoccali, C
Oxidative medicine and cellular longevity. 2017;:2801324
Abstract
Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r = 0.71, P < 0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198.
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Advanced glycation end products (AGEs) and the soluble receptor for AGE (sRAGE) in patients with type 1 diabetes and coeliac disease.
Bakker, SF, Tushuizen, ME, Gözütok, E, Çiftci, A, Gelderman, KA, Mulder, CJ, Simsek, S
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2015;(2):230-5
Abstract
BACKGROUND AND AIMS Advanced glycation end (AGE) products play a role in the progression of diabetic complications. Gluten-free diet (GFD) might affect AGE levels in patients who adhere to a GFD because of coeliac disease (CD). The aim of our study was to compare skin AGE levels and soluble receptor AGE levels (sRAGE) in patients with type 1 diabetes (T1DM) with (T1DM + CD) and without CD (T1DM - CD) and healthy controls. METHODS AND RESULTS We recruited 25 T1DM + CD and 25 T1DM - CD patients, matched for age, gender, diabetes duration, and glycaemic control alongside 25 healthy controls. We collected demographic, clinical and biochemical characteristics, including skin autofluorescence (AF), sRAGE and hs-CRP levels. The duration of T1DM in patients was 30 ± 14 (+CD) and 29 ± 14 years (-CD), whereas CD duration in T1DM + CD patients was 14 ± 10 years. Skin AF levels in T1DM patients were higher compared to healthy controls (2.5 ± 0.6 versus 1.9 ± 0.4, p < 0.01) and skin AF was independently associated with age (r = 0.72, p < 0.01). sRAGE levels were higher in T1DM - CD patients compared to healthy controls (1554 ± 449 versus 1309 ± 400, p = 0.049) and independently associated with creatinine levels (r = 0.32, p < 0.01). CONCLUSION Our study demonstrates that skin AGE and sRAGE levels are elevated in T1DM patients compared with healthy controls. No difference in skin AF or sRAGE levels between T1DM patients with or without CD were observed. The present study suggests that differences in microvascular complications between T1DM and T1DM + CD patients are not due to differences in skin AF or sRAGE levels.
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The HMG-CoA reductase inhibitor cerivastatin lowers advanced glycation end products in patients with type 2 diabetes.
Scharnagl, H, Stojakovic, T, Winkler, K, Rosinger, S, März, W, Boehm, BO
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2007;(6):372-5
Abstract
Although the association between type 2 diabetes mellitus (DM) and cardiovascular diseases is well-documented, current knowledge regarding reasons for the increased prevalence of atherosclerosis in DM is incomplete. Advanced glycosylation end-products (AGE) may play an important role in the development of atherosclerosis in diabetic patients. We examined the effect of the HMG-CoA reductase inhibitor (HMGRI) cerivastatin on serum concentration of AGE-CML in patients with elevated fasting glucose, impaired glucose tolerance or DM. The study was a multicenter, double-blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for 12 weeks (n=34) and placebo (n=35). Patients were characterized by combined hyperlipoproteinemia and the preponderance of dense LDL. Primary objective of the study was the effect of cerivastatin on the concentration of dense LDL subfractions. Here we report on the effect of cerivastatin on the concentration of AGE-CML. After 12 weeks of treatment cerivastatin reduced cholesterol, apolipoprotein B, LDL cholesterol and the concentration of dense LDL. Furthermore, cerivastatin significantly lowered the concentration of AGE-CML by 21% ( P=0,005; compared to -7,5% in the placebo group). The effect on AGE-CML was correlated with the reduction in LDL cholesterol (r=0.355, P=0.003) and LDL apoB (r=0.239, P=0.05). In addition to the lipid-lowering effects of HMGRI, the reduction of AGE-CML observed in our study may entail an improvement of the cardiovascular prognosis in patients with chronic hyperglycemia.