scholarly journals High dietary glycemic load is associated with higher concentrations of urinary advanced glycation endproducts: the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) Study

2019 ◽  
Vol 110 (2) ◽  
pp. 358-366 ◽  
Author(s):  
Kim Maasen ◽  
Marleen M J van Greevenbroek ◽  
Jean L J M Scheijen ◽  
Carla J H van der Kallen ◽  
Coen D A Stehouwer ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Advanced Glycation Endproducts ◽  
Glycemic Load ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Dietary Factors ◽  
Oral Glucose ◽  
Advanced Glycation ◽  
Cross Sectional ◽  
Glycation Endproducts

ABSTRACT Background Advanced glycation endproducts (AGEs) and their precursors (dicarbonyls) are associated with the progression of diseases such as diabetes and cardiovascular disease. Plasma concentrations of dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) are increased after an oral glucose load indicating that consumption of diets high in carbohydrates may induce the endogenous formation of dicarbonyls and AGEs. Objective To examine the associations of dietary glycemic index (GI) and glycemic load (GL) with concentrations of dicarbonyls and AGEs in plasma and urine. Methods Cross-sectional analyses were performed in a human observational cohort [Cohort on Diabetes and Atherosclerosis Maastricht (CODAM), n = 494, 59 ± 7 y, 25% type 2 diabetes]. GI and GL were derived from FFQs. Dicarbonyls and AGEs were measured in the fasting state by ultra-performance liquid chromatography-tandem MS. MGO, GO, and 3-DG and protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and pentosidine were measured in plasma. Free forms of CML, CEL, and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured in both plasma and urine. Multiple linear regression was performed with dicarbonyls and AGEs as dependent variables, and dietary GI or GL as main independent variables (all standardized). Models were adjusted for health and lifestyle factors, dietary factors, and reciprocally for GI and GL. As this was an explorative study, we did not adjust for multiple testing. Results GI was not associated with any of the dicarbonyls or AGEs. GL was positively associated with free urinary MG-H1 (β = 0.34; 95% CI: 0.12, 0.55). Furthermore, GL was positively associated with free plasma MG-H1 and free urinary CML (β = 0.23; 95% CI: 0.02, 0.43; and β = 0.28; 95% CI: 0.06, 0.50), but these associations were not independent of dietary AGE intake. Conclusions A habitual diet higher in GL is associated with higher concentrations of free urinary MG-H1. This urinary AGE is most likely a reflection of AGE accumulation and degradation in tissues, where they may be involved in tissue dysfunction.

scholarly journals Effects of Advanced Glycation Endproducts on the Mechanical Properties of Posterior Tibialis in Individuals with Diabetes Mellitus

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0045
Author(s):  
Jennifer A. Zellers ◽  
Jeremy Eekhoff ◽  
Remy Walk ◽  
Simon Y. Tang ◽  
Mary K. Hastings ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Mechanical Properties ◽  
Mechanical Testing ◽  
Advanced Glycation Endproducts ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Advanced Glycation ◽  
Cross Sectional ◽  
Glycation Endproducts ◽  
Wet Weight

Category: Diabetes Introduction/Purpose: Advanced glycation endproducts (AGEs) accumulate in tendon tissue in individuals with diabetes mellitus (DM). Although AGEs have been shown to impact tendon function by decreasing collagen sliding, this relationship has not been explored in humans with diabetes. Despite the prevalence of foot deformity in this population and implications of posterior tibialis dysfunction, the mechanical behavior of the posterior tibialis tendon has only been reported in a small (n=5), cadaveric study that did not report DM status. Therefore, the purpose of this study is to determine the effects of DM-associated AGEs accumulation on the mechanical properties of the posterior tibialis tendon. Methods: Posterior tibialis tendons were collected from individuals with and without DM undergoing lower extremity amputation. A 1-2 mm tendon transection was used for AGEs quantification. AGEs were quantified via fluorescence following papain digestion and hydrolyzation as described previously. Fluorescence was compared to a quinine standard to calculate AGEs content, which was normalized to sample wet weight. Tensile mechanical testing was completed with the remaining specimen (˜25 mm long). Tendon cross-sectional area was measured with a non-contact laser scanning device. Specimens were preloaded to 10 N and preconditioned for 10 cycles at 6% strain, subjected to stress-relaxation at 6% strain for 10 minutes, and loaded with a triangular waveform to a maximum of 10% strain at a rate of 1% strain per second. Individual values and group descriptive statistics are reported for AGEs content and mechanical testing. Relationships between AGEs content and various mechanical testing parameters were evaluated using Spearman correlation. Results: Six individuals (5 with DM, 4 male, mean(SD) age: 56(5)years) were included. AGEs content was increased in DM tendon (DM: 20.5(5.1), non-DM: 9.5 ng quinine/mg wet weight). Compared to non-DM tendon, DM tendons had larger cross-sectional area (DM: 44.3(4.9), non-DM: 11mm2). From stress relaxation, DM tendons had smaller peak (DM: 0.41(0.25), non-DM: 1.16 MPa) and equilibrium stress (DM: 0.23(0.13), non-DM: 0.83 MPa), and larger percent relaxation (DM: 46(6)%, non-DM: 29%)(Figure 1-A). DM tendons had decreased maximum stress at 10% strain (DM: 0.63(0.45), non-DM: 1.75 MPa), increased linear stiffness (DM: 35.2(27.6), non-DM: 19.2N/mm), and decreased linear modulus (DM: 8.5(7.0), non-DM: 20.1 MPa)(Figure 1-B, C) compared to non- DM tendon. Hysteresis (i.e., energy loss upon unloading) was higher in DM tendons (DM: 0.35(0.05), non-DM: 0.22), and positively correlated to AGEs (rho=0.943, p=0.005, Figure 1-D). Conclusion: Posterior tibialis tendons with DM exhibited increased AGEs content and altered mechanical properties. DM tendons were less stiff when accounting for cross-sectional area but had 2-4x the cross-sectional area of non-DM tendon, with inconsistent patterns in total tendon stiffness potentially attributable to several factors. DM tendons showed impaired energy storage and return, which was most strongly associated with AGEs. Non-DM samples were limited and the linear modulus was smaller than previously reported, however, all but one DM tendon had a modulus less than 50% of the non-DM sample. Future work will explore the mechanisms of AGEs-associated DM tendon impairments.

scholarly journals Polymorphisms in Glyoxalase I Gene Are Not Associated with Glyoxalase I Expression in Whole Blood or Markers of Methylglyoxal Stress: The CODAM Study

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 219
Author(s):  
Kim Maasen ◽  
Nordin M. J. Hanssen ◽  
Carla J. H. van der Kallen ◽  
Coen D. A. Stehouwer ◽  
Marleen M. J. van Greevenbroek ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Advanced Glycation Endproducts ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glyoxalase I ◽  
Glycation Endproducts ◽  
Fasting Plasma ◽  
Age Related ◽  
Rate Limiting

Glyoxalase 1 (Glo1) is the rate-limiting enzyme in the detoxification of methylglyoxal (MGO) into D-lactate. MGO is a major precursor of advanced glycation endproducts (AGEs), and both are associated with development of age-related diseases. Since genetic variation in GLO1 may alter the expression and/or the activity of Glo1, we examined the association of nine SNPs in GLO1 with Glo1 expression and markers of MGO stress (MGO in fasting plasma and after an oral glucose tolerance test, D-lactate in fasting plasma and urine, and MGO-derived AGEs CEL and MG-H1 in fasting plasma and urine). We used data of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM, n = 546, 60 ± 7 y, 25% type 2 diabetes). Outcomes were compared across genotypes using linear regression, adjusted for age, sex, and glucose metabolism status. We found that SNP4 (rs13199033) was associated with Glo1 expression (AA as reference, standardized beta AT = −0.29, p = 0.02 and TT = −0.39, p = 0.3). Similarly, SNP13 (rs3799703) was associated with Glo1 expression (GG as reference, standardized beta AG = 0.17, p = 0.14 and AA = 0.36, p = 0.005). After correction for multiple testing these associations were not significant. For the other SNPs, we observed no consistent associations over the different genotypes. Thus, polymorphisms of GLO1 were not associated with Glo1 expression or markers of MGO stress, suggesting that these SNPs are not functional, although activity/expression might be altered in other tissues.

scholarly journals Advanced glycation endproducts and dicarbonyls in end-stage renal disease: associations with uraemia and courses following renal replacement therapy

2019 ◽  
Vol 13 (5) ◽  
pp. 855-866
Author(s):  
Remy J H Martens ◽  
Natascha J H Broers ◽  
Bernard Canaud ◽  
Maarten H L Christiaans ◽  
Tom Cornelis ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Advanced Glycation Endproducts ◽  
Advanced Glycation ◽  
Cvd Risk ◽  
Cross Sectional ◽  
Glycation Endproducts ◽  
Ckd Stage ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background End-stage renal disease (ESRD) is strongly associated with cardiovascular disease (CVD) risk. Advanced glycation endproducts (AGEs) and dicarbonyls, major precursors of AGEs, may contribute to the pathophysiology of CVD in ESRD. However, detailed data on the courses of AGEs and dicarbonyls during the transition of ESRD patients to renal replacement therapy are lacking. Methods We quantified an extensive panel of 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)], serum dicarbonyls [glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG)] and tissue AGE accumulation [estimated by skin autofluorescence (SAF)] in a combined cross-sectional and longitudinal observational study of patients with ESRD transitioning to dialysis or kidney transplantation (KTx), prevalent dialysis patients and healthy controls. Cross-sectional comparisons were performed with linear regression analyses, and courses following renal replacement therapy were analysed with linear mixed models. Results Free and protein-bound AGEs, dicarbonyls and SAF were higher in chronic kidney disease (CKD) Stage 5 non-dialysis (CKD 5-ND; n = 52) and CKD Stage 5 dialysis (CKD 5-D; n = 35) than in controls (n = 42). In addition, free AGEs, protein-bound CML, GO and SAF were even higher in CKD 5-D than in CKD5-ND. Similarly, following dialysis initiation (n = 43) free and protein-bound AGEs, and GO increased, whereas SAF remained similar. In contrast, following KTx (n = 21), free and protein-bound AGEs and dicarbonyls, but not SAF, markedly declined. Conclusions AGEs and dicarbonyls accumulate in uraemia, which is even exaggerated by dialysis initiation. In contrast, KTx markedly reduces AGEs and dicarbonyls. Given their associations with CVD risk in high-risk populations, lowering AGE and dicarbonyl levels may be valuable.

Higher habitual intake of dietary dicarbonyls is associated with higher corresponding plasma dicarbonyl concentrations and skin autofluorescence: The Maastricht Study

2021 ◽  
Author(s):  
Kim Maasen ◽  
Simone J P M Eussen ◽  
Jean L J M Scheijen ◽  
Carla J H van der Kallen ◽  
Pieter C Dagnelie ◽  
...  
Keyword(s):  
Advanced Glycation Endproducts ◽  
Plasma Concentrations ◽  
Population Based ◽  
Skin Autofluorescence ◽  
Linear Regression Models ◽  
Clinical Trial Registry ◽  
Cross Sectional ◽  
Glycation Endproducts ◽  
Age Related ◽  
Habitual Intake

Abstract Background Dicarbonyls are highly reactive compounds and major precursors of advanced glycation endproducts (AGEs). Both dicarbonyls and AGEs are associated with development of age-related diseases. Dicarbonyls are formed endogenously, but also during food processing. To what extent dicarbonyls from the diet contribute to circulating dicarbonyls and AGEs in tissues is unknown. Objective To examine cross-sectional associations of dietary dicarbonyl intake with plasma dicarbonyl concentrations and skin AGEs. Design In 2566 individuals of the population based Maastricht Study (age: 60±8 yrs, 50% males, 26% type 2 diabetes), we estimated habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), by combining Food Frequency Questionnaires with our dietary dicarbonyl database of MGO, GO, and 3-DG concentrations in >200 commonly-consumed food products. Fasting plasma concentrations of MGO, GO, and 3-DG were measured by UPLC-MS/MS. Skin AGEs were measured as skin autofluorescence (SAF), using the AGE-Reader. Associations of dietary dicarbonyl intake with their respective plasma concentrations and SAF (all standardized) were examined using linear regression models, adjusted for age, sex, potential confounders related to cardio-metabolic risk factors and lifestyle. Results Median intake of MGO, GO, and 3-DG was 3.6, 3.5, and 17 mg/day, respectively. Coffee was the main dietary source of MGO, whereas this was bread for GO and 3-DG. In the fully adjusted models, dietary MGO was associated with plasma MGO (β = 0.08, 95%CI [0.02,0.13]) and SAF (β = 0.12 [0.07,0.17]). Dietary GO was associated with plasma GO (β = 0.10 [0.04,0.16]) but not with SAF. 3-DG was not significantly associated with either plasma 3-DG or SAF. Conclusions Higher habitual intake of dietary MGO and GO, but not 3-DG, was associated with higher corresponding plasma concentrations. Higher intake of MGO was also associated with higher SAF. These results suggest dietary absorption of MGO and GO. Biological implications of dietary absorption of MGO and GO need to be determined. Clinical Trial Registry number: The study has been approved by the institutional medical ethical committee (NL31329.068.10) and the Minister of Health, Welfare and Sports of the Netherlands (Permit 131088-105234-PG).

scholarly journals The Immune Tolerance Role of the HMGB1-RAGE Axis

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 564
Author(s):  
Haruki Watanabe ◽  
Myoungsun Son
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Lupus Erythematosus ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Chromatin Binding ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Extracellular Milieu

The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.

scholarly journals Is skin autofluorescence (SAF) representative of dermal advanced glycation endproducts (AGEs) in dark skin? A pilot study

Heliyon ◽  
2020 ◽  
Vol 6 (11) ◽  
pp. e05364
Author(s):  
Isabella M. Atzeni ◽  
Jeltje Boersema ◽  
Hendri H. Pas ◽  
Gilles F.H. Diercks ◽  
Jean L.J.M. Scheijen ◽  
...  
Keyword(s):  
Pilot Study ◽  
Advanced Glycation Endproducts ◽  
Skin Autofluorescence ◽  
Advanced Glycation ◽  
Dark Skin ◽  
Glycation Endproducts
Sign in / Sign up

Export Citation Format

Share Document