-
1.
Phytate Decreases Formation of Advanced Glycation End-Products in Patients with Type II Diabetes: Randomized Crossover Trial.
Sanchis, P, Rivera, R, Berga, F, Fortuny, R, Adrover, M, Costa-Bauza, A, Grases, F, Masmiquel, L
Scientific reports. 2018;(1):9619
Abstract
Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant in cereals, legumes, and nuts and it has the ability to chelate metal cations. The binding of IP6 to transition metals suggests that it could be used for the treatment of metal-catalyzed protein glycation, which appears to trigger diabetes-related diseases. Our in vitro studies showed that IP6 reduced the formation of Fe3+-catalyzed advanced glycation end-products (AGEs). This led us to perform a randomized cross-over trial to investigate the impact of the daily consumption IP6 on protein glycation in patients with type 2 diabetes mellitus (T2DM; n = 33). Thus, we measured AGEs, glycated hemoglobin (HbA1c), several vascular risk factors, and urinary IP6 at baseline and at the end of the intervention period. Patients who consumed IP6 supplements for 3 months had lower levels of circulating AGEs and HbA1c than those who did not consume IP6. This is the first report to show that consumption of IP6 inhibits protein glycation in patients with T2DM. Considering that AGEs contribute to microvascular and macrovascular complications in T2DM, our data indicates that dietary supplementation with IP6 should be considered as a therapy to prevent the formation of AGEs and therefore, the development of diabetes-related diseases in patients with T2DM.
-
2.
AGE Content of a Protein Load Is Responsible for Renal Performances: A Pilot Study.
Normand, G, Lemoine, S, Villien, M, Le Bars, D, Merida, I, Irace, Z, Troalen, T, Costes, N, Juillard, L
Diabetes care. 2018;(6):1292-1294
Abstract
OBJECTIVE Chronic kidney disease is associated with higher morbidity and mortality in patients with diabetes. A low-protein diet is recommended to slow diabetic nephropathy progression because each protein load leads to renal hemodynamic variations. The aim of our study was to evaluate whether the advanced glycation end products (AGE) content of a protein load is responsible for the protein-induced renal hemodynamic variations in humans. RESEARCH DESIGN AND METHODS Ten healthy subjects were assigned to a high-protein (1 g/kg) low-AGE (3,000 kU AGE) versus high-AGE (30,000 kU AGE) meal. Renal perfusion, oxygen consumption, and oxygen content were measured before and 120 min after each meal. RESULTS Renal perfusion (3.2 ± 0.5 vs. 3.8 ± 0.4 mL/min/g; P = 0.0002) and oxygen consumption (0.3 ± 0.04 vs. 0.4 ± 0.08 min-1; P = 0.005) increased significantly after the high-AGE meal compared with the low-AGE meal. CONCLUSIONS Our results suggest that the AGE content of a protein load is responsible for renal hemodynamic modifications. Therefore, prevention of diabetic nephropathy progression could aim predominantly at reducing food AGE content.
-
3.
Involvement of Advanced Glycation End Products in the Pathogenesis of Diabetic Retinopathy.
Xu, J, Chen, LJ, Yu, J, Wang, HJ, Zhang, F, Liu, Q, Wu, J
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2018;(2):705-717
Abstract
Diabetic retinopathy (DR) is a common and devastating microvascular complication of diabetes and a major cause of acquired blindness in young adults. Advanced glycation end products (AGEs) accumulated under hyperglycemic conditions are thought to play an important role in the pathogenesis of DR. AGEs can exert their deleterious effects by acting directly to induce aberrant crosslinking of extracellular matrix proteins, to increase vascular stiffness, altering vascular structure and function. Moreover, AGEs binding to the receptor for AGEs (RAGE) evokes intensive intracellular signaling cascades that leading to endothelial dysfunction, elaboration of key proinflammatory cytokines and proangiogenic factors, mediating pericyte apoptosis, vascular inflammation and angiogenesis, as well as breakdown of the inner blood-retinal barrier (BRB), the end result of all these events is damage to the neural and vascular components of the retina. Elucidation of AGE-induced mechanisms will help in the understanding of the complex cellular and molecular pathogenesis associated with DR. Novel anti-AGEs agents or AGE crosslink "breakers" are being investigated, it is hoped that in next few years, some of these promising therapies will be successfully applied in clinical context, aiming to reduce the major economical and medical burden caused by DR.
-
4.
AGE-RAGE Interaction Does Not Explain the Clinical Improvements after Therapeutic Fasting in Osteoarthritis.
Drinda, S, Franke, S, Schmidt, S, Stoy, K, Lehmann, T, Wolf, G, Neumann, T
Complementary medicine research. 2018;(3):167-172
Abstract
BACKGROUND Therapeutic fasting improves joint pain in patients with osteoarthritis (OA), but the underlying mechanisms are unknown. Interactions of advanced glycation end products (AGEs) and their receptors (RAGE) play a role in OA pathogenesis. This study aimed to investigate whether the benefits of fasting in OA can be explained by changes in AGEs or RAGE. PATIENTS AND METHODS 37 patients with OA underwent fasting for 8 days. Serum levels of an AGE (N-ε-(carboxymethyl)-lysine; CML) and the soluble RAGE (sRAGE) as well as clinical outcome parameters such pain characteristics (measured by visual analogue scale; VAS), joint function (determined by the Western Ontario and McMaster Universities Arthritis Index; WOMAC), and quality of life (via the 36-Item Short-Form Health Survey (SF-36) questionnaire) were assessed. The variables were measured at baseline, the end of fasting, and at follow-up at 4 weeks. RESULTS The CML levels did not significantly change from baseline to the end of intervention (Δ = -25.6 ± 92.2 ng/ml; p = 0.10). In contrast, the sRAGE levels (Δ = -182.7 ± 171.4 ng/ml; p < 0.0001) and the sRAGE/CML ratio (Δ = -0.4 ± 0.6; p < 0.001) significantly decreased, but they returned to baseline levels 4 weeks after the end of fasting. The scores for pain, WOMAC, and the physical subscale of the SF-36 significantly improved during fasting. There was no correlation between the clinical outcomes and changes in serum levels of CML, sRAGE, or the sRAGE/CML ratio. CONCLUSIONS Fasting resulted in a significant but non-sustained reduction of sRAGE levels and the sRAGE/CML ratio in OA, while the CML levels did not change. Improvement in clinical endpoints of OA does not correlate with changes in CML or sRAGE.
-
5.
Studies of advanced glycation end products and oxidation biomarkers for type 2 diabetes.
Chiu, CJ, Rabbani, N, Rowan, S, Chang, ML, Sawyer, S, Hu, FB, Willett, W, Thornalley, PJ, Anwar, A, Bar, L, et al
BioFactors (Oxford, England). 2018;(3):281-288
-
-
Free full text
-
Abstract
Advanced glycation end products (AGEs) are formed upon nonenzymatic reactions of sugars or their metabolites with proteins and other cellular constituents. Many AGEs are long lived. Recent findings suggest that AGEs may predict diabetes and its complications and thus may warrant further study. The objective of this study was to assess the validity of our experimental procedures for measuring AGEs in stored blood sample and to conduct a pilot study for developing AGE biomarkers for diabetes and/or age-related changes of glucose metabolism. We conducted a reliability study of the samples and methods using liquid chromatography-tandem mass spectrometry (LC-MS)/MS assays for 10 AGEs (including methylglyoxal-derived hydroimidazolone (MG-H1), glucosepane (GSP) and two oxidation measures, in stored repository blood samples from the Nurses' Health Study and the Health Professionals Follow-up Study. We also analyzed data relating blood GSP levels to type 2 diabetes status in a case-control study (25 cases and 15 controls). Among the AGEs, GSP, and MG-H1 showed the highest reliability across the various measures: reliability in duplicate samples and stability with delayed processing and storage over 1-2 year period. Furthermore, plasma GSP was associated with older age (P = 0.04) and type 2 diabetes status (age-adjusted P = 0.0475). Our findings suggest that analysis of these AGEs may be developed as biomarkers for diabetes and/or age-related changes of glucose metabolism. © 2018 BioFactors, 44(3):281-288, 2018.
-
6.
Dietary advanced glycation end products and their relevance for human health.
Nowotny, K, Schröter, D, Schreiner, M, Grune, T
Ageing research reviews. 2018;:55-66
Abstract
Due to their bioactivity and harmful potential, advanced glycation end products (AGEs) are discussed to affect human health. AGEs are compounds formed endogenously in the human body andexogenously, especially, in foods while thermal processing. In contrast to endogenous AGEs, dietary AGEs are formed in much higher extent. However, their risk potential is also depending on absorption, distribution, metabolism and elimination. For over 10 years an intense debate on the risk of dietary AGEs on human health is going on. On the one hand, studies provided evidence that dietary AGEs contribute to clinical outcomes. On the other hand, human studies failed to observe any association. Because it was not possible to draw a final conclusion, the call for new interdisciplinary approaches arose. In this review, we will give an overview on the current state of scientific knowledge in this field. In particular, we focus on (I) the occurrence of AGEs in foods and the daily uptake of AGEs, (II) contribution to endogenous levels and (III) the effect on health-/disease-related biomarkers in humans.
-
7.
l-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products, and tumor necrosis factor-α levels in patients with type 2 diabetes: a double-blind placebo-controlled randomized clinical trial.
Houjeghani, S, Kheirouri, S, Faraji, E, Jafarabadi, MA
Nutrition research (New York, N.Y.). 2018;:96-106
Abstract
Considering the pathologic importance of metabolic disturbances, advanced glycation end products (AGEs), and chronic inflammation in diabetes mellitus and ameliorating potentials of l-carnosine in hampering these detritions and because these effects have not been investigated in patients with type 2 diabetes (T2D) so far, we conducted the current study. We hypothesized that l-carnosine would improve glycemic control, lipid profile, AGE, soluble receptor of AGEs (sRAGE), and inflammatory markers. In a randomized, double-blind, placebo-controlled clinical trial, 54 patients with T2D were recruited and assigned into either intervention group (n=27, receiving 2 capsules of l-carnosine 500 mg each) or control group (n=27). Blood samples and dietary intakes information were collected at baseline and after 12 weeks of intervention. l-Carnosine supplementation resulted in significant decrease in fat mass and an increase in fat-free mass in the intervention group compared with the placebo group (1.5% and 1.7%, respectively) (P<.05). A significant reduction in fasting blood glucose (13.1 mg/dL); glycated hemoglobin (.6%); and serum levels of triglycerides (29.8 mg/dL), carboxymethyl lysine (91.8 ng/mL), and tumor necrosis factor-α was detected in the l-carnosine group compared with the placebo group (P<.05). In the l-carnosine group, a significant reduction in serum pentosidine levels (2.8 ng/mL) was observed compared with those at baseline (P<.05). No significant differences were observed in dietary intake, body mass index, systolic and diastolic blood pressure, fasting insulin levels, homeostasis model assessment of insulin resistance and secretion, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sRAGE, interleukin (IL)-6, and IL-1β levels between the groups after adjusting for baseline values and covariates (P>.05). Collectively, l-carnosine lowered fasting glucose, serum levels of triglycerides, AGEs, and tumor necrosis factor-α without changing sRAGE, IL-6, and IL-1β levels in T2D patients.
-
8.
Mediterranean Diet Supplemented With Coenzyme Q10 Modulates the Postprandial Metabolism of Advanced Glycation End Products in Elderly Men and Women.
Lopez-Moreno, J, Quintana-Navarro, GM, Delgado-Lista, J, Garcia-Rios, A, Alcala-Diaz, JF, Gomez-Delgado, F, Camargo, A, Perez-Martinez, P, Tinahones, FJ, Striker, GE, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2018;(3):340-346
Abstract
Advanced glycation end products (AGEs) and oxidative stress are elevated with aging and dysmetabolic conditions. Because a Mediterranean (Med) diet reduces oxidative stress, serum AGEs levels, and gene expression related to AGEs metabolism in healthy elderly people, we studied whether supplementation with coenzyme Q10 (CoQ) was of further benefit. Twenty participants aged ≥ 65 (10 men and 10 women) were randomly assigned to each of three isocaloric diets for successive periods of 4 weeks in a crossover design: Med diet, Med + CoQ, and a Western high-saturated-fat diet (SFA diet). After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to the previous diet period. Analyses included dietary AGEs consumed, serum AGEs and AGE receptor-1 (AGER1), receptor for AGEs (RAGE), glyoxalase I (GloxI), and estrogen receptor α (ERα) mRNA levels. Med diet modulated redox-state parameters, reducing AGEs levels and increasing AGER1 and GloxI mRNA levels compared with the SFA diet. This benefit was accentuated by adding CoQ, in particular, in the postprandial state. Because elevated oxidative stress/inflammation and AGEs are associated with clinical disease in aging, the enhanced protection of a Med diet supplemented with CoQ should be assessed in a larger clinical trial in which clinical conditions in aging are measured.
-
9.
Skin autofluorescence, a non-invasive marker of advanced glycation end products: clinical relevance and limitations.
Da Moura Semedo, C, Webb, M, Waller, H, Khunti, K, Davies, M
Postgraduate medical journal. 2017;(1099):289-294
Abstract
Advanced glycation end products (AGEs) are protein-bound compounds derived from glycaemic and oxidative stress that contain fluorescent properties, which can be non-invasively measured as skin autofluorescence (SAF) by the AGE Reader. SAF has been demonstrated to be a biomarker of cumulative skin AGEs and potentially may be a better predictor for the development of chronic complications and mortality in diabetes than glycated haemoglobin A1c. However, there are several confounding factors that should be assessed prior to its broader application: these include presence of other fluorescent compounds in the skin that might be measured (eg, fluorophores), skin pigmentation and use of skin creams. The aim of this article is to provide a theoretical background of this newly developed method, evaluate its clinical relevance and discuss the potential confounding factors that need further analysis.
-
10.
Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls.
Fokkens, BT, Mulder, DJ, Schalkwijk, CG, Scheijen, JL, Smit, AJ, Los, LI
PloS one. 2017;(3):e0173379
Abstract
PURPOSE Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. METHODS We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 non-diabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and 5-hydro-5-methylimidazolone) and α-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. RESULTS Mean age was 64 ± 7.6 years for T2DM patients and 63 ± 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3-7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 μmol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and α-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). CONCLUSIONS Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients.