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Background: Glycated albumin (GA) levels have been considered as a promising biomarker for estimating glycemic control during pregnancy, but the relationship between GA levels and the incidence of adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains unclear. Our study aimed to investigate the relationship between GA levels during the third trimester and 13 different adverse pregnancy-related outcomes among women with GDM in China., Methods: We retrospectively extracted clinical data from the medical records of 819 pregnant women with GDM who underwent prenatal examinations and child delivery at the Affiliated Hospital of Qingdao University between January 2022 and October 2022. The cohort was divided into GA-high (GA-H) and GA-low (GA-L) groups based on the median GA level of 10.6%. Then, the incidence rates of 13 specific adverse pregnancy outcomes were compared between the two groups. Furthermore, we estimated the mean GA levels in pregnant GDM women with or without specific adverse outcomes. Multivariate logistic regression analysis was performed to assess whether the GA levels (high or low) were independent risk factors for specific adverse outcomes in pregnant women with GDM. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of GA levels for the adverse pregnant outcomes in women with GDM. E-value for sensitivity analysis was performed to assess the robustness of the findings to unmeasured confoundings., Results: We included 819 pregnant women with GDM, whose average age was 33.09 ± 4.47 years, average pre-pregnancy BMI was 23.51 ± 3.67 kg/m 2 , and the average gestational week in which GDM diagnosed was 24.80 ± 1.79 weeks. The analysis showed that 80.71% (661/819) pregnant women with GDM were associated with adverse pregnancy-related outcomes. Pregnant women in the GA-L group showed higher incidence of the premature rupture of membranes (PROM), whereas those in the GA-H group showed higher incidence of neonatal hypoglycemia. The GA levels showed acceptable clinical performance for predicting neonatal hypoglycemia with an area under the ROC curve (AUC) value of 0.700 (P = 0.010), sensitivity of 71.4%, and specificity of 70.2%. The optimal cut off value for GA was 11.55%., Conclusions: This study demonstrated that GA levels were significantly associated with specific adverse pregnancy outcomes, especially PROM and neonatal hypoglycemia. Furthermore, GA levels in the third trimester showed acceptable clinical performance for predicting neonatal hypoglycemia among pregnant women with GDM. In the future, the potential role of GA as a predictor of adverse pregnancy outcomes need to be further confirmed and explored in GDM women., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University (No. QYFY WZLL 28129). Because of the retrospective nature of the study, informed patient consent was waived by the Ethics Committee of the Affiliated Hospital of Qingdao University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Glycated albumin (GA) has shown promise in predicting risk of adverse neonatal outcomes (ANO) in pregnant women with type 2 diabetes (T2DM) and gestational diabetes (GDM). However, previous studies showing a negative correlation between GA and body mass index (BMI) suggest that lower predictive cutoffs may be needed in populations with elevated BMI., Methods: We performed a case-control study of prospectively enrolled pregnant women with T2DM or GDM and BMI ≥25 kg/m2 matched to biobanked controls without diabetes. Serum collected during the second and/or third trimesters was used to measure the percentage of GA (% GA). Receiver operating characteristic (ROC) curves were used to examine % GA to predict an ANO composite, including macrosomia, hypoglycemia, respiratory distress syndrome, and/or hyperbilirubinemia for the second and third trimesters., Results: The median BMIs for cases and controls were 34.0 and 31.0 kg/m2, respectively. The area under the ROC curve to predict the ANO composite was significant for second trimester values but ambiguous for third trimester due to its wide 95% CI. A cutoff of 12.3% GA during second trimester showed 100% sensitivity and 73% specificity. Transference of previously published reference ranges did not validate, suggesting lower ranges are needed for women with overweight/obesity., Conclusions: In this pilot study, % GA shows promise to stratify pregnant patients with diabetes and obesity into risk categories for ANO with excellent predictive ability in the second trimester. If this holds in larger studies, using second trimester % GA could allow additional intervention to improve blood glucose control and minimize ANO., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Glycated Albumin (GA) and atherogenic index of plasma (AIP) are two important biomarkers that respectively reflect lipid and glucose levels. Previous research has revealed their roles in cardiovascular diseases (CVD) and diabetes. However, their combined predictive ability in forecasting cardiovascular events (CVE) after percutaneous coronary intervention (PCI) among postmenopausal acute coronary syndrome (ACS) patients remains insufficiently studied., Methods: Based on the levels of AIP (AIP-L and AIP-H) and GA (GA-L and GA-H), four groups were used to categorize the patients. The CVE assessed included cardiac death, nonfatal myocardial infarction (MI) and nonfatal stroke. To evaluate the relationship between AIP, GA, and CVE, multivariate Cox regression analyses were performed., Results: 98 patients (7.5%) experienced CVE during follow-up. AIP and GA were revealed as strong independent predictors of CVE through multivariate analysis (AIP: HR 3.324, 95%CI 1.732-6.365, P = 0.004; GA: HR 1.098, 95% CI 1.023-1.177, P = 0.009). In comparison to those in the initial group (AIP-L and GA-L), the fourth group (AIP-H and GA-H) of patients exhibited the greatest CVE risk (HR 2.929, 95% CI 1.206-5.117, P = 0.018). Derived from the model of baseline risk, the combination of AIP + GA significantly enhanced the AUC, meanwhile combining AIP and GA levels maximized prognostic accuracy in the baseline risk model., Conclusions: This study found that the combined measurement of AIP and GA significantly enhanced the predictive capability for CVE following PCI in postmenopausal ACS patients. By integrating these two biomarkers, it became possible to more accurately identify high-risk individuals and provided clinicians with new predictive tools for postmenopausal ACS patients in risk assessment and management., (© 2024. The Author(s).)

Background: Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD)., Methods: 1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal-MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention., Results: The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p < 0.001). The Mediterranean diet, but not the low-fat diet, produced an upregulation of AGE metabolism, with increased AGER1 and GloxI gene expression as well as increased GSH and sRAGE levels in Non-increased IMT-CC patients (all p < 0.05). Although the Mediterranean diet increased MG levels in Increased IMT-CC patients, this increment was lower compared to the low-fat diet (all p < 0.05)., Conclusions: Our results suggest that an improvement in modulation of AGE metabolism, which facilitates better management of circulating AGE levels, may be one of the mechanisms through which the Mediterranean diet, compared to a low-fat diet, reduces the progression of atherosclerosis in patients with CHD. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 , Clinicaltrials.gov number, NCT00924937., (© 2024. The Author(s).)

Background: Advanced glycation end products (AGEs), a group of food processing byproducts, have been implicated in the development of various diseases. However, the relationship between circulating AGEs and sleep disorders remains uncertain., Methods: This cross-sectional study elucidated the association of plasma AGEs with sleep disorders among 1732 Chinese adults who participated in the initial visit (2019-2020) of the Tongji-Shenzhen Cohort (TJSZC). Sleep behavior was assessed using self-reported questionnaires and precise accelerometers. Plasma levels of AGEs, including Nε-(Carboxymethyl)lysine (CML), Nε-(Carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1), were quantified by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)., Results: In logistic regression, per IQR increment in individual AGEs was associated with an increased odds ratio of short sleep duration (CML: 1.11 [1.00, 1.23]; CEL: 1.16, [1.04, 1.30]), poor sleep quality (CML: 1.33 [1.10, 1.60]; CEL: 1.53, [1.17, 2.00]; MG-H1: 1.61 [1.25, 2.07]), excessive daytime sleepiness (CML: 1.33 [1.11, 1.60]; MG-H1: 1.39 [1.09, 1.77]), and insomnia (CML: 1.29 [1.05, 1.59]). Furthermore, in weighted quantile sum regression and Bayesian kernel machine regression analyses, elevated overall exposure levels of plasma AGEs were associated with an increased risk of sleep disorders, including short sleep duration, poor sleep quality, excessive daytime sleepiness, and insomnia, with CML being identified as the leading contributor. Insufficient vegetable intake and higher dietary fat intake was associated with an increase in plasma CEL., Conclusions: These findings support a significant association between plasma AGEs and sleep disorders, indicating that AGEs may adversely influence sleep health and reducing the intake of AGEs may facilitate preventing and ameliorating sleep disorders.

Background: In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium., Methods: A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4-36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates., Results: FMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R 2  = 0.31, P < 0.001., Conclusions: Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers., Trial Registration: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number., (© 2024. The Author(s).)

Background and Aim: Glycated albumin (GA) is a biomarker monitoring glycemia 2-4 weeks before stroke onset. This study was designed to explore the association between GA levels with poststroke outcomes in patients with acute ischemic stroke or transient ischemic attack (TIA)., Method: Participants with ischemic stroke or TIA who had a baseline GA measurement were included in the Third China National Stroke Registry study. The effect of GA on stroke recurrence, poor functional outcomes, and combined vascular events was examined during the 1-year follow-up period. Multivariate Cox and logistic regression models were performed to evaluate the association. Discrimination tests were used to examine the incremental predictive value of GA when incorporating it into the conventional model., Results: A total of 3861 participants were enrolled. At the 3-month follow-up, the elevated GA level was associated with an increased risk of poor functional outcomes (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.01-2.09). A similar increase was observed for stroke recurrence (adjusted hazard ratio [HR], 1.56; 95% CI, 1.09-2.24), poor functional outcomes (adjusted OR, 1.62; 95% CI, 1.07-2.45), and combined vascular events (adjusted HR, 1.55; 95% CI, 1.09-2.20) at the 1-year follow-up. In nondiabetic patients, the association between GA and poor functional outcomes was more pronounced (adjusted OR, 1.62; 95% CI, 1.05-2.50). Adding GA into the conventional model resulted in slight improvements in predicting poor functional outcomes (net reclassification improvement [NRI]: 12.30% at 1 year)., Conclusion: This study demonstrated that elevated GA levels in serum were associated with stroke adverse outcomes, including stroke recurrence, poor functional outcomes, and combined vascular events, in patients with ischemic stroke or TIA., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To investigate associations of plasma glycated albumin (GA) concentrations in early and midpregnancy with gestational diabetes mellitus (GDM) risk., Research Design and Methods: We measured GA concentrations using blood samples collected at 10-14 and 15-26 weeks' gestation in 107 GDM case and 214 control participants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. We performed generalized linear mixed-effect regression to test the mean GA difference between GDM case and control participants and conditional logistic regression to assess prospective associations between GA concentrations and GDM risk., Results: At 15-26 weeks' gestation mean GA was lower in GDM case participants than in control participants (mean 11.90% [95% CI 6.42-32.76] vs. 12.46% [8.45-38.35], adjusted P value for difference = 0.004). Consistently, women with higher GA concentrations tended to have a lower GDM risk, although the associations were not statistically significant., Conclusions: This study suggests that GA concentrations in midpregnancy might be lower in women who later develop GDM. Further studies are needed to identify the mechanism., (© 2024 by the American Diabetes Association.)

Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, N ε -[carboxy-methyl]lysine (CML), N ε -[carboxy-ethyl]lysine (CEL) and N δ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (P interaction  = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HR Q5vs.Q1  = 1.67, 95% CI: 1.21-2.30, P trend  = .02) or any cause (HR Q5vs.Q1  = 1.38, 95% CI: 1.05-1.83, P trend  = .09). These associations tended to be stronger among cases with diabetes (P interaction  = .03) and pre-diabetes (P interaction  <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes., (© 2024 UICC.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease with a high fatality rate. Although several nomograms based on demographic and laboratory data have been reported to predict the prognosis of SFTS in recent studies, baseline serum glycated albumin (GA)/albumin (ALB) ratio included risk model has not been evaluated for the prediction of clinical outcome., Methods: A total of 214 SFTS patients with integral data admitted to our hospital from May, 2020 to November, 2022 were included in this study. SFTS infection was confirmed by real time fluorescent quantitative PCR (qRT-PCR). The demographic characteristics, clinical and laboratory data were collected with in 24 h of admission and 1 to 2 days before discharge and were analysed retrospectively., Results: Fiffty-seven patients (26.6%) died. Multivariate logistic regression analysis showed that age, aspartate aminotransferase (AST), blood glucose (GLU), GA/ALB ratio, neutrophil counts (NEU) and lymphocyte percentage (LYM%) were the independent risk factors for mortality. A nomogram by these factors was created using RMS package in the R program. Area under the receiver operating characteristic (ROC) curve (AUC) of this nomogram was 0.88 (95% CI: 0.83, 0.93). This model showed the excellent net benefit, as revealed by the decision curve analysis. GA/ALB ratios were also independent risk factors for poor out clinical come in subgroups of patients with hyperglycemia on admission and with diabetes history. Nomograms were constructed by the independent risk factors in the subgroups. AUCs of the nomograms in the subgroups showed high predictive values for adverse prognosis., Conclusions: GA/ALB ratios were independent risk factors for mortality in all SFTS patients and subgroups of with hyperglycemia on admission and diabetes history. The nomograms including GA/ALB ratio had high predictive value for adverse clinical outcome.The nomograms provide a basis for clinical decision-making for the treatment of SFTS patients in different clinical settings., (© 2024. The Author(s).)

Advanced glycation end-products (AGEs) formation increases with metabolic disorders, leading to higher serum AGE levels in patients with progressive vascular complications. Measuring AGE levels in biological samples requires multiple pre-analytical processing steps, rendering analysis of multiple samples challenging. This study evaluated the progression of diabetic complications by analyzing AGE levels using a pre-analytical processing strategy based on a fully automated solid phase-extraction system. Serum samples from patients with diabetes, with or without macrovascular complications (Mac or non-Mac) or microvascular complications (Mic or non-Mic), were processed with the established methods. Free and total AGE levels in sera were measured using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In patients with diabetes, both free and total AGE levels were elevated in those with complications compared to those without complications. In Mac and Mic groups, free and total AGE levels and z-scores (the sum of normalized AGE levels) also increased. AGE z-scores were markedly higher than those of single AGE levels in distinguishing each complication. Our study demonstrated that the free AGE z-score, measured using a new analytical method without hydrolysis, correlated with the presence of vascular complications and may serve as a marker of disease complications., (© 2024. The Author(s).)

Introduction: Patients on hemodialysis, especially with diabetes, face elevated cardiovascular events. A major contributor to complications associated with diabetes is advanced glycation end products (AGEs). Removing these compounds is challenging in traditional hemodialysis. Medium-cut-off (MCO) membranes potentially remove toxins without significant albumin loss. This study explored how MCO membranes impact AGEs levels in uncontrolled diabetic patients undergoing hemodialysis., Methods: Sixteen patients received MCO membrane dialysis, while others used high-flux (HF) membranes. After 12 sessions, the dialyzers were switched, totaling 24 sessions. Blood samples at trial initiation (T0), session 12 (T1) and session 24 (T2) tested for CML, Pentosidine, laboratory parameters., Results: Switching dialyzers showed increased albumin with MCO-to-HF and decreased with HF-to-MCO, albeit nonsignificant (p = 0.5/p = 0.1). Patients on MCO had lower albumin levels than HF (p = 0.03/p = 0.6, respectively). Hemodialysis with MCO demonstrated lower levels of CML/Pentosidine compared to HF (p = 0.09/p = 0.9 for CML; p = 0.04/p = 0.3 for Pentosidine). Transitioning to HF led to elevated levels (p = 0.4/p = 0.09 for CML; p = 0.3/p = 0.07 for Pentosidine)., Conclusion: MCO dialysis in diabetic individuals notably reduces AGE levels., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Background and Aims: Previous studies have shown that skin autofluorescence (SAF), measured with an advanced glycation end product (AGE) reader, estimates the accumulation of AGEs in tissues. SAF is predictive of incident type 2 diabetes, cardiovascular disease (CVD), and CV mortality in the general population. Studies in diabetic mice have shown that activation of the receptor for AGEs in hematopoietic progenitor cells increases blood neutrophils and monocytes, impairing atherosclerosis regression. We asked whether SAF is associated with blood neutrophil and monocyte counts in the general population, and whether this was moderated by prediabetes, diabetes, and sex., Methods: We examined the associations between SAF and blood neutrophil/monocyte counts in participants of the Lifelines cohort (n = 58,923: n = 24,382 men, and n = 34,541 women), a prospective population-based cohort from the North of the Netherlands, employing multivariable regression analyses., Results: SAF positively associated with blood neutrophil and monocyte counts in the whole cohort. The positive association between SAF and monocyte, but not neutrophil, counts was moderated by prediabetes and diabetes. Positive associations between SAF and blood neutrophil and monocyte counts were moderated by male sex. Moreover, three-way interaction analyses revealed that the positive associations between SAF and neutrophil and monocyte counts were moderated by prediabetes, but not diabetes, in male sex., Conclusions: SAF is positively associated with blood neutrophil and monocyte counts in the general population, especially in men with prediabetes. This may contribute to the increased CV risk in men with prediabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of the study was to evaluate the association of the quality of diet as calculated by the Nutrient Rich Food index (NRF9.3), and length of service (LS) (≤10 years vs. >10 years) with selected serum biochemical parameters, the proportions of different lipid profile fractions and advanced glycation endproduct (AGE) values of 108 firefighters from the State Fire Service in Wroclaw. The LS officers > 10 years had significantly higher total cholesterol (211.50 (184.00-254.00) vs. 184.00 (166.00-194.00)), LDL (123.75 (108.20-167.90) vs. 105.18 (90.24-119.00)) non-HDL (151.70 (132.00-196.70) vs. 122.00 (106.00-140.00)), triglycerides (118.50 (96.00-158.00) vs. 78.00 (67.00-103.00)) and lower HDL concentrations (51.30 (45.60-56.70) vs. 58.00 (51.70-66.10)) compared to firefighters in the LS ≤ 10 years group. Significant differences between the seniority groups were also noted for all lipid profile ratios. Regardless of the officers' seniority, systolic blood pressure was observed at the highest normal level of 134.4 ± 14.4 in the LS ≤ 10 years group and 139.5 ± 14.3 in the LS > 10 years group. Advanced glycation endproduct values were significantly dependent on diet quality, as expressed by the NRF9.3 index and on the TG/HDL ratio, but not on seniority. Diet quality, as expressed by the NRF9.3 index, had a significant association with GLU and FI levels, and components of the lipid profile between seniority groups. As NRF9.3 increased, TG/HDL, LDL/HDL, TC/HDL, and non-HDL/HDL ratios decreased. AGEs were significantly affected by NRF9.3 and significantly associated with TG/HDL. Firefighters' diets, as assessed by the NRF9.3 index, had a significant association with predictors of insulin resistance, diabetes, and cardiometabolic predictors between seniority groups. The nutritional education of firefighters (and other professional groups working irregularly), especially those with longer tenure (e.g., >10 years), is necessary to prevent the development of, e.g., CVD, MetS, and T2DM, which contribute towards a reduced ability to perform professional duties.

Aim: To clarify the role of advanced glycation end products (AGEs) and inflammation in the development of vascular calcification and cardiovascular complications at different stages of chronic kidney disease (CKD) G1-G5D., Materials and Methods: We examined 105 patients aged 19 to 75 years with stage C1-C5D CKD, 77 (74%) of whom were patients with diabetic nephropathy. The concentration of AGEs, interleukin (IL)-1, IL-6 and tumor necrosis factor α (TNF-α), troponin I, parathyroid hormone was determined by enzyme-linked immunosorbent assay (ELISA) using kits from BluGene biotech (Shanghai, China), Cloud-Clone Corp. (USA), ELISA Kit (Biomedica, Austria)., Results: A high content of AGEs, IL-1, IL-6, TNF-α was established, which directly correlated with the increase in renal failure and changes in the morpho-functional parameters of the left ventricle and aorta., Conclusion: An increase in serum concentrations of AGEs and inflammatory mediators, correlating with a decrease in renal function and changes in the morpho- functional parameters of the left ventricle and aorta, indicate their significant role in the processes of damage to the cardiovascular system in CKD.

Background: Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes., Methods: Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m 2 /year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death., Results: Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR., Conclusions: Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications., (© 2024. The Author(s).)

The effect of calcium (Ca) on glycation markers is unknown. We hypothesized that increased Ca intake from skimmed milk associated with an energy-restricted diet intake will reduce glycation markers. This reduction will be associated with a greater improvement in markers of metabolic control in adults with type 2 diabetes, overweight, and low habitual Ca intake (<600 mg/d). In this secondary data analysis based on a crossover clinical trial, 14 adults were allocated into 2 groups: high calcium (shake containing 700 mg Ca/day) or low calcium (shake with 6.4 mg Ca/day), for 12 consecutive weeks per session. Energy-restricted diets were also prescribed (-500 kcal/d, 800 mg of dietary Ca/d) to all participants. Advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), glycemic control, and lipid profile were assessed at baseline and after 12 weeks. High-calcium serum AGE concentrations and AGE/sRAGE ratio were lower at the end of the study. ΔAGE and ΔAGE/sRAGE ratio were both positively associated with Δtriglycerides, Δtotal cholesterol, Δtriglyceride-glucose index and variations, and Δvisceral adiposity index. ΔAGE/sRAGE was positively associated with Δfructosamine and Δhigh-density lipoprotein-cholesterol, and negatively associated with male sex. Consumption of approximately 1200 mg/day of calcium (3 servings of skim milk) reduced serum AGEs concentrations and the AGE/sRAGE ratio in individuals with diabetes. In general, positive changes in glycation markers are associated with lipid profile, insulin resistance, and adiposity markers worsening. ΔAGEs/ΔsRAGE ratio seems to be a better marker of metabolic status than ΔAGEs and ΔsRAGE alone. Registered in ClinicalTrials.gov (NCT02377076)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The frequency of sudden death and its risk factors in patients undergoing hemodialysis are unknown. This study was performed to examine the association between glycated albumin (GA) and sudden death in Japanese patients undergoing hemodialysis., Methods: In total, 260 patients undergoing hemodialysis aged ≥18 years were retrospectively followed for a mean of 4.6 years. The patients' serum GA levels were divided into tertiles, and the patients' sex, age, albumin level, C-reactive protein (CRP) level, and cardiothoracic ratio (CTR) were selected as adjustment factors. A logistic regression model was used to calculate the odds ratio (OR) for the occurrence of sudden death by GA level., Results: Ninety-one patients died during follow-up. Of the 91 deaths, 23 (25.2%) were defined as sudden deaths. Compared with non-sudden death cases, sudden death cases were significantly younger (p = 0.002) and had a higher proportion of men (p = 0.03), a higher proportion of diabetes (p = 0.008), and higher GA levels (p = 0.023). Compared with patients with the lowest GA levels (<15.2%), those with the highest GA levels (≥18.5%) had a sex- and age-adjusted OR for sudden death of 5.40 [95% confidence interval (CI): 1.35-21.85]. After adjusting for the albumin level, CRP level, and CTR in addition to sex and age, the OR for sudden death of patients with the highest GA levels increased to 6.80 (95%CI: 1.64-28.08); the relationship did not change., Conclusion: Serum GA levels were significantly associated with sudden death in patients undergoing hemodialysis., (© 2024. The Author(s).)

Background: Age, genetic, and environmental factors are noted to contribute to dementia risk. Neuroplasticity, protection from degeneration and cell death, and early intervention are desirable for preventing dementia. The linkage between neurons and microglia has been a research focus. In this study, we examined the effects of dietary modification (a reduction in advanced glycation end products [AGEs]) and macrophage-activating factor (MAF; a macrophage regulator) supplementation on cognitive function in elderly participants undergoing rehabilitation., Methods: Participants were older than 60 years of age and had been attending a daycare rehabilitation facility for at least three months without cognitive dysfunction, severe anemia, terminal cancer, or neurodegenerative diseases such as Parkinson's disease. The exercise protocol at the rehabilitation facility was not changed during the study period. Forty-three participates were randomly divided into three groups: a control group receiving placebo, a group receiving dietary guidance, and a group receiving dietary guidance and MAF supplementation. The amyloid-β40/42 ratio, dietary AGE intake, plasma AGE levels, dietary caloric intake, and mild cognitive impairment (MCI) screen test were evaluated., Results: Four participants withdrew from the study. MCI screening scores significantly improved in the MAF supplementation group, especially after 6 months. Dietary modulation was also more effective than placebo at improving cognitive function after 12 months. Only the control group exhibited significantly increased plasma AGEs while the dietary modulation and MAF supplementation groups showed no change in plasma AGEs after 12 months., Conclusions: MAF supplementation improved cognitive function, especially after 6 months, in elderly people undergoing rehabilitation. Dietary modulation was also effective for improving cognitive function after 12 months compared to that in the control group. It was difficult to supervise meals during dietary guidance at the daycare service. However, simple guidance could show improvements in cognitive function through diet.

Background: Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting more than 95% of people with diabetes. Traditionally, some medicinal plants have been considered as an effective approach in management of T2DM. This trial evaluated the effects of date seed powder (DSP) on glycemia indices and oxidative stress in T2DM patients., Methods: In this trail, 43 patients with T2DM were randomized to two groups: either 5 g/d of the DSP or placebo for 8 weeks. Levels of glycemic indices, lipolpolysaccharide (LPS), and soluble receptor for advanced glycation end products (s-RAGE), as well as other parameters associated with oxidative stress were assessed at baseline and after 8 weeks. Independent t-test and analysis of covariance (ANCOVA) were used for between-groups comparisons at baseline and the post-intervention phase, respectively., Results: The results showed that supplementation with DSP significantly decreased HbA1c (-0.30 ± 0.48%), insulin (-1.70 ± 2.21 μU/ml), HOMA-IR (-1.05 ± 0.21), HOMA-B (-0.76 ± 21.21), lipopolysaccharide (LPS) (-3.68 ± 6.05 EU/mL), and pentosidine (118.99 ± 21.67 pg/mL) (P < 0.05, ANCOVA adjusted for baseline and confounding factors). On the other hand, DSP supplementation significantly increased total antioxidant capacity (TAC) (0.50 ± 0.26 mmol/L), superoxide dismutase (SOD) (0.69 ± 0.32 U/ml), and s-RAGE (240.13 ± 54.25 pg/mL) compared to the placebo group. FPG, hs-CRP, GPx, CML, and uric acid had no significant within- or between-group changes., Conclusion: Supplementation of DSP could be considered an effective strategy to improve glycemic control and oxidative stress in T2DM patients (Registration ID at www.irct.ir : IRCT20150205020965N10)., (© 2024. The Author(s).)

Glycated albumin (GA) reflects glycemic status for the past three weeks. GA level demonstrates a strong correlation with HbA1c level and is used as an adjunctive biomarker for diagnosis and monitoring of type 2 diabetes mellitus (T2DM). In this study, we validated the predictive performance of baseline GA for development of T2DM in healthy individuals in Korea. From August 2013 to September 2014, the medical records of 3,771 healthy Koreans were retrospectively reviewed. Each participant was categorized into tertiles based on initial GA level. During the follow-up period through May 2020, study participants were evaluated for T2DM using HbA1c, fasting glucose level, and a self-reported diagnosis history. Baseline GA level by tertile (T1 to T3) was 10.4 ± 0.8% (mean ± SD), 12.1 ± 0.3%, and 13.7 ± 0.9%, respectively. The median follow-up was 5.97 years, during which 4.9% (186 of 3,771) of the participants developed T2DM. After adjusting for confounding factors, the hazard ratio for the development of T2DM in the highest GA level group (T3) compared to the reference group (T1) was 2.46 (95% CI, 1.7 to 3.58, p  < 0.001 for trend) with a Harrell's C index of 0.80 (95% CI, 0.76 to 0.83). Also, within highest group of baseline HbA1c and FG levels, higher GA levels were associated with an increased HRs for T2DM. In conclusion, Our study confirms that the risk of T2DM increases with baseline GA level. Additional follow-up of the cohort is warranted to investigate the correlations between GA and other clinical indicators including diabetic complications.

Advanced glycation end products (AGEs), formed via the Maillard reaction (MR) during processing of foods, have been implicated in inflammatory and degenerative diseases in human beings. Cellular damage is primarily caused by AGE binding with the receptor for AGEs (RAGE) on cell membranes. An isoform of RAGE, soluble RAGE (sRAGE), acts as a decoy receptor binding circulating AGEs preventing cellular activation. Pet food manufacturing involves processing methods similar to human food processing that may increase dietary AGEs (dAGEs). We hypothesized that diet, plasma and urine AGEs, and serum sRAGE concentrations would differ between thermally processed diets. This study examined the association of four differently processed diets: ultra-processed canned wet food (WF); ultra-processed dry food (DF); moderately processed air-dried food (ADF) and minimally processed mildly cooked food (MF) on total plasma levels of the AGEs, carboxymethyllysine (CML), carboxyethyllysine (CEL), methylglyoxal hydroimidazolone-1, glyoxal hydroimidazolone-1, argpyrimidine, urine CML, CEL and lysinoalanine, and serum sRAGE concentration. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure AGEs. sRAGE concentration was measured using a commercial canine-specific enzyme-linked immunosorbent assay kit. Total dAGEs (mg/100 kcal as fed) were higher in WF than in other diets. Plasma total AGEs (nM/50 μL) were significantly higher with WF, with no difference found between DF, ADF, and MF; however, ADF was significantly higher than MF. Urine CML (nmol AGEs/mmol creatinine) was significantly higher with DF than with WF and MF. There were no significant differences in total urine AGEs or serum sRAGE concentration between diets. In conclusion, different methods of processing pet foods are associated with varied quantities of AGEs influencing total plasma AGE concentration in healthy dogs. Serum sRAGE concentration did not vary across diets but differences in total AGE/sRAGE ratio were observed between MF and WF and, ADF and DF., (© 2024 The Authors. Journal of Animal Physiology and Animal Nutrition published by Wiley‐VCH GmbH.)

Nitrosative stress promotes protein glycoxidation, and both processes can occur during an infection with the SARS-CoV-2 virus. Therefore, the aim of this study was to assess selected nitrosative stress parameters and protein glycoxidation products in COVID-19 patients and convalescents relative to healthy subjects, including in reference to the severity of COVID-19 symptoms. The diagnostic utility of nitrosative stress and protein glycoxidation biomarkers was also evaluated in COVID-19 patients. The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects. Nitrosative stress parameters (NO, S-nitrosothiols, nitrotyrosine) and protein glycoxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, AGEs) were measured in the blood plasma or serum with the use of colorimetric/fluorometric methods. The levels of NO (p = 0.0480), S-nitrosothiols (p = 0.0004), nitrotyrosine (p = 0.0175), kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan fluorescence was significantly (p < 0.0001) lower in COVID-19 patients than in the control group. Significant differences in the analyzed parameters were observed in different stages of COVID-19. In turn, the concentrations of kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan levels were significantly (p < 0.0001) lower in convalescents than in healthy controls. The ROC analysis revealed that protein glycoxidation products can be useful for diagnosing infections with the SARS-CoV-2 virus because they differentiate COVID-19 patients (KN: sensitivity-91.20%, specificity-92.00%; NFK: sensitivity-92.37%, specificity-92.00%; AGEs: sensitivity-99,02%, specificity-100%) and convalescents (KN: sensitivity-82.22%, specificity-84.00%; NFK: sensitivity-82,86%, specificity-86,00%; DT: sensitivity-100%, specificity-100%; AGE: sensitivity-100%, specificity-100%) from healthy subjects with high sensitivity and specificity. Nitrosative stress and protein glycoxidation are intensified both during and after an infection with the SARS-CoV-2 virus. The levels of redox biomarkers fluctuate in different stages of the disease. Circulating biomarkers of nitrosative stress/protein glycoxidation have potential diagnostic utility in both COVID-19 patients and convalescents., (© 2024. The Author(s).)

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder in children. It is currently diagnosed by behaviour-based assessments made by observation and interview. In 2018 we reported a discovery study of a blood biomarker diagnostic test for ASD based on a combination of four plasma protein glycation and oxidation adducts. The test had 88% accuracy in children 5-12 years old. Herein, we present an international multicenter clinical validation study (N = 478) with application of similar biomarkers to a wider age range of 1.5-12 years old children. Three hundred and eleven children with ASD (247 male, 64 female; age 5.2 ± 3.0 years) and 167 children with typical development (94 male, 73 female; 4.9 ± 2.4 years) were recruited for this study at Sidra Medicine and Hamad Medical Corporation hospitals, Qatar, and Hospital Regional Universitario de Málaga, Spain. For subjects 5-12 years old, the diagnostic algorithm with features, advanced glycation endproducts (AGEs)-N ε -carboxymethyl-lysine (CML), N ω -carboxymethylarginine (CMA) and 3-deoxyglucosone-derived hydroimidazolone (3DG-H), and oxidative damage marker, o,o'-dityrosine (DT), age and gender had accuracy 83% (CI 79 - 89%), sensitivity 94% (CI 90-98%), specificity 67% (CI 57-76%) and area-under-the-curve of receiver operating characteristic plot (AUROC) 0.87 (CI 0.84-0.90). Inclusion of additional plasma protein glycation and oxidation adducts increased the specificity to 74%. An algorithm with 12 plasma protein glycation and oxidation adduct features was optimum for children of 1.5-12 years old: accuracy 74% (CI 70-79%), sensitivity 75% (CI 63-87%), specificity 74% (CI 58-90%) and AUROC 0.79 (CI 0.74-0.84). We conclude that ASD diagnosis may be supported using an algorithm with features of plasma protein CML, CMA, 3DG-H and DT in 5-12 years-old children, and an algorithm with additional features applicable for ASD screening in younger children. ASD severity, as assessed by ADOS-2 score, correlated positively with plasma protein glycation adducts derived from methylglyoxal, hydroimidazolone MG-H1 and N ε (1-carboxyethyl)lysine (CEL). The successful validation herein may indicate that the algorithm modifiable features are mechanistic risk markers linking ASD to increased lipid peroxidation, neuronal plasticity and proteotoxic stress., (© 2023. The Author(s).)

Background: The current research on advanced glycosylation end products (AGEs) and cognitive function is limited., Objective: We aimed to investigate the relationship between multiple plasma AGEs and cognitive function and mild cognitive impairment (MCI)., Methods: Baseline data from The Lifestyle and Healthy Aging of Chinese Square Dancer Study was used in this cross-sectional study. Ultra-high-performance liquid chromatography tandem mass spectrometry was used to determine plasma levels of carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and methyl imidazolinone (MG-H1). Four cognitive tests were used to obtain the four cognitive domain scores and the composite z scores. The Petersen criteria were used to diagnose MCI. The data were analyzed by multivariable linear and logistic regression models., Results: This study included 1,018 participants (median age 61.0 years, 87.3% female). After multivariate adjustment, the βs of the highest quartile of CML and CEL compared to the lowest quartile were -0.28 (-0.38, -0.17) and -0.13 (-0.23, -0.03), respectively, for the composite z score. For the four cognitive domains, CML was negatively correlated with memory, attention, and executive function, and CEL was negatively associated with memory and language function. In addition, higher CML was associated with a higher odds of MCI. MG-H1 was not associated with cognitive function., Conclusions: High plasma AGE levels were correlated with poorer cognitive function, particularly CML and CEL, higher levels of CML were also associated with higher odds of MCI. To clarify the effects of different AGEs on cognitive function and the underlying mechanisms, further longitudinal and experimental studies are needed.

Objective: Diabetes and prediabetes are growing concerns among US youth. Fasting glucose (FG) and HbA1c are standard diabetes screening tests, but HbA1c may be unreliable in some settings and fasting is burdensome in children. Glycated albumin (GA) is a non-fasting test that was recently cleared for clinical use in the United States, but studies in youth without diabetes are limited., Research Design and Methods: We conducted a cross-sectional analysis in 6826 youth without diabetes aged 8-19 years in the 1999-2004 National Health and Nutrition Examination Survey. We evaluated the associations of GA with HbA1c, FG, and cardiometabolic risk factors., Results: GA was poorly correlated with HbA1c (ρ = 0.074) and FG (ρ = -0.047) and was negatively associated with body mass index (BMI) and cardiometabolic risk factors. Compared to youth in the highest tertile of GA (≥13.5%), those in the lowest GA tertile (<12.4%) had a higher prevalence of obesity (29.9% vs. 7.6%), low high-density lipoprotein cholesterol (29.7% vs. 16.5%), and hypertensive blood pressure (4.0% vs. 2.7%). These inverse associations persisted after adjustment for age, sex, race/ethnicity, serum albumin, and C-reactive protein., Conclusions: GA was poorly correlated with traditional markers of hyperglycemia in youth without diabetes. Counterintuitively, there was a negative association between GA and BMI. Among youth without diabetes, GA does not identify youth at high cardiometabolic risk, and it does not appear to be an appropriate biomarker for screening of hyperglycemia., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Higher soluble receptor for advanced glycation end product (sRAGE) levels are considered to be associated with severe emphysema. However, the relationship remains uncertain when the advanced glycation end-product specific receptor (AGER) gene is involved. We aimed to analyse the association between sRAGE levels and emphysema according to the genotypes of rs2070600 in the AGER gene., Methods: We genotyped rs2070600 and measured the plasma concentration of sRAGE in each participant. Emphysema was quantified based on the chest computed tomography findings. We compared sRAGE levels based on the presence or absence and severity of emphysema in each genotype. Multiple logistic and linear regression models were used for the analyses., Results: A total of 436 participants were included in the study. Among them, 64.2% had chronic obstructive pulmonary disease and 34.2% had emphysema. Among the CC-genotyped participants, the sRAGE level was significantly higher in participants without emphysema than in those with emphysema (P < 0.001). In addition, sRAGE levels were negatively correlated with emphysema severity in CC-genotyped patients (r = - 0.268 P < 0.001). Multiple regression analysis revealed that sRAGE was an independent protective factor for the presence of emphysema (adjusted odds ratio, 0.24; 95% confidence interval (CI) 0.11-0.51) and severity of emphysema (β = - 3.28, 95% CI - 4.86 to - 1.70) in CC-genotyped participants., Conclusion: Plasma sRAGE might be a biomarker with a protective effect on emphysema among CC-genotyped patients of rs2070600 on the AGER gene. This is important in determining the target group for the future prediction and treatment of emphysema., (© 2022. The Author(s).)

Profiling of advanced glycation end products (AGEs) is an emerging area of clinical significance for disease diagnosis and prognosis. Typically, concentrations of AGEs are estimated in laboratories by trained personnel using sophisticated equipment. Herein, a facile approach for colorimetric and fluorometric profiling of AGEs is reported for rapid and on-site analysis. The concentrations of AGE levels in plasma are estimated via changes in optical properties of polythiophenes (PTs) upon interaction with aptamers (Apts) in the presence and in the absence of AGEs. To validate the proposed approach, glyceraldehyde-derived AGEs (AGE class 1 [AGE1]), the biomarker associated with cardiovascular diseases and diabetes, are used as a model system. Colorimetric analysis yielded linear responses for AGE1 for clinically relevant concentration ranges between 1.5 and 300 μg/mL with a limit of detection (LOD) of ∼1.3 μg/mL. Subsequently, an approach utilizing PTs with four different pendant groups in conjunction with four different Apts is demonstrated for qualitative colorimetric profiling and for quantitative fluorometric profiling of up to four AGEs in clinical matrices. Principal component analysis (PCA) of fluorometric responses of AGE-spiked samples yielded distinct responses for the different AGEs tested. Thus, the proposed approach ascertains rapid profiling of spiked AGEs in plasma samples without the requirement of preanalytical processing and advanced instrumentation, thereby facilitating on-site diagnosis.

We evaluated the impact of prestroke glycemic variability estimated by glycated albumin (GA) on symptomatic hemorrhagic transformation (SHT) in patients with intravenous thrombolysis (IVT). Using a multicenter database, we consecutively enrolled acute ischemic stroke patients receiving IVT. A total of 378 patients were included in this study. Higher GA was defined as GA ≥ 16.0%. The primary outcome measure was SHT. Multivariate regression analysis and a receiver operating characteristic curve were used to assess risks and predictive ability for SHT. Among the 378 patients who were enrolled in this study, 27 patients (7.1%) had SHT as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SHT SITS ). The rate of SHT SITS was higher in the higher GA group than in the lower GA group (18.0% vs. 1.6%, p < 0.001). A higher GA level (GA ≥ 16.0%) significantly increased the risk of SHT SITS (adjusted odds ratio [OR], [95% confidence interval, CI], 12.57 [3.08-41.54]) in the logistic regression analysis. The predictive ability of the GA level for SHT SITS was good (AUC [95% CI]: 0.83 [0.77-0.90], p < 0.001), and the cutoff value of GA in SHT was 16.3%. GA was a reliable predictor of SHT after IVT in acute ischemic stroke in this study., (© 2022. The Author(s).)

Background: Dicarbonyls are highly reactive compounds and major precursors of advanced glycation end products (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., Objectives: To examine cross-sectional associations of dietary dicarbonyl intake with plasma dicarbonyl concentrations and skin AGEs., Methods: In 2566 individuals of the population-based Maastricht Study (age: 60 ± 8 y, 50% males, 26% with type 2 diabetes), we estimated habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by combining FFQs 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 ultra-performance liquid chromatography-tandem mass spectrometry. 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 cardiometabolic risk factors, and lifestyle., Results: Median intake of MGO, GO, and 3-DG was 3.6, 3.5, and 17 mg/d, 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; 95% CI: 0.07, 0.17). Dietary GO was associated with plasma GO (β: 0.10; 95% CI: 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. 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)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Systemic lupus erythematosus (SLE) is characterized by abnormal action of the immune system and a state of chronic inflammation. The disease can cause life-threatening complications. Neoepitopes arising from interdependent glycation and oxidation processes might be an element of SLE pathology. The groups included in the study were 31 female SLE patients and 26 healthy female volunteers (the control group). Blood serum samples were obtained to evaluate concentrations of advanced glycation end-products (AGEs), carboxymethyllysine (CML), carboxyethyllysine (CEL), pentosidine, and a soluble form of the receptor for advanced glycation end-products (sRAGE). Compared to a healthy control group, the SLE patients exhibited a higher concentration of AGEs and a lower concentration of sRAGE in serum. There were no statistically significant differences in serum CML, CEL, and pentosidine concentrations between the groups. Therefore, SLE patients could be at risk of intensified glycation process and activation of the proinflammatory receptor for advanced glycation end-products (RAGE), which could potentially worsen the disease course; however, it is not clear which compounds contribute to the increased concentration of AGEs in the blood. Additionally, information about the cigarette smoking and alcohol consumption of the study participants was obtained.

Objective: The research is to investigate the expression and the relationship between serum endothelial cell-specific molecular molecule-1 (ESM-1), high molecular weight adiponectin (HMWA), and late glycosylation terminal product (AGEs) in patients with gestational hypertension., Methods: 75 patients with pregnant hypertension who were treated in our hospital from June 2019 to June 2020 were selected as the case group, and 70 healthy pregnant women with pregnancy examination at the same period in our hospital were selected as the control group to analyze the changes in serum ESM-1, HMWA, and AGEs levels and the correlation with the degree of illness and their predictive value., Results: Serum ESM-1 and AGEs were significantly higher in the case group than in the control group. Serum HMWA was significantly lower than that in the control group ( P < 0.05). The gestational hypertensive serum ESM-1 and AGEs was significantly lower than in patients with mild preeclampsia and severe preeclampsia. Serum HMWA was significantly higher than in patients with mild preeclampsia and severe preeclampsia. Serum ESM-1 and AGEs of mild preeclampsia were significantly lower than in patients with severe preeclampsia. Serum HMWA was significantly higher than in patients with severe preeclampsia ( P < 0.05). The result of correlation analysis shows a positive correlation between serum ESM-1 and AGEs ( P < 0.05). A negative correlation was observed between HMWA and the degree of illness ( P < 0.05)., Conclusion: Serum ESM-1, HMWA, and AGEs are abnormally expressed in gestational hypertension, are closely related to the degree of condition, and have important clinical significance for condition control., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yun Yan et al.)

Materials and Methods: We included 132 subjects (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm. The device enables single and automated triplicate measurements: both of these were performed. DSPN was diagnosed through the neuropathy disability score (NDS). Small nerve fibre function was assessed by temperature and pinprick sensation on the foot. Bilateral measurement of the vibration perception threshold (VPT) on the hallux was carried out by using a neurothesiometer (Horwell Scientific Laboratory Supplies)., Results: Single and triplicate AGE measurements were positively correlated with each other (Pearson's correlation coefficient r = 0.991, 95%CI = 0.987-0.994, p < 0.001). AGEs were higher among subjects with vs. those without DSPN ( p < 0.001). Furthermore, they were higher among subjects with reduced vs. normal temperature sensation ( p < 0.001), among subjects with reduced vs. normal pinprick sensation ( p = 0.002), among those with abnormal vs. normal monofilament examination ( p < 0.001), and among those with abnormal vs. normal VPT ( p < 0.001). AGEs were correlated with NDS, VPT, and monofilament score., Conclusions: In T2DM, skin AGEs are increased in the presence of DSPN. This holds true both for large and for small nerve function impairment. Moreover, AGEs are correlated with DSPN severity., Competing Interests: NP has been an advisory board member of Astra-Zeneca, Boehringer Ingelheim, MSD, Novo Nordisk, Pfizer, Takeda, and TrigoCare International; has participated in sponsored studies by Astra-Zeneca, Eli-Lilly, GSK, MSD, Novo Nordisk, Novartis, and Sanofi-Aventis; has received honoraria as a speaker for Astra-Zeneca, Boehringer Ingelheim, Eli-Lilly, Elpen, MSD, Mylan, Novo Nordisk, Pfizer, Sanofi-Aventis, and Vianex; and attended conferences sponsored by TrigoCare International, Eli-Lilly, Galenica, Novo Nordisk, Pfizer, and Sanofi-Aventis. The other authors report no conflicts of interest., (Copyright © 2021 Stella Papachristou et al.)

A declined salivary gland function is commonly observed in elderly people. Advanced glycation end products (AGEs) are believed to contribute to the pathogenesis of aging. Although physical exercise is shown to increase various organ functions in human and experimental models, it is not known whether it has a similar effect in the salivary glands. In the present study, we evaluated the AGEs burden in the salivary gland in the aging process and the protective effect of physical exercise on age-related salivary hypofunction. To accelerate the aging process, rats were peritoneally injected with D-galactose for 6 weeks. Young control rats and d-galactose-induced aging rats in the old group were not exercised. The rats in the physical exercise group ran on a treadmill (12 m/min, 60 min/day, 3 days/week for 6 weeks). The results showed that the salivary flow rate and total protein levels in the saliva of the d-galactose-induced aging rats were reduced compared to those of the young control rats. Circulating AGEs in serum and secreted AGEs in saliva increased with d-galactose-induced aging. AGEs also accumulated in the salivary glands of these aging rats. The salivary gland of aging rats showed increased reactive oxygen species (ROS) generation, loss of acinar cells, and apoptosis compared to young control mice. However, physical exercise suppressed all of these age-related salivary changes. Overall, physical exercise could provide a beneficial option for age-related salivary hypofunction.

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., (© 2021. The Author(s).)

Purpose: Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD., Methods: From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury., Results: The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057-9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023-0.290) and 0.474 (0.213-1.109) μg/mL, P = 0.001]., Conclusion: Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arginine (Arg) and lysine (Lys) moieties of proteins undergo various post-translational modifications (PTM) including enzymatic N G - and N ε -methylation and non-enzymatic N G - and N ε -glycation. In a large cohort of stable kidney transplant recipients (KTR, n = 686), high plasma and low urinary concentrations of asymmetric dimethylarginine (ADMA), an abundant PTM metabolite of Arg, were associated with cardiovascular and all-cause mortality. Thus, the prediction of the same biomarker regarding mortality may depend on the biological sample. In another large cohort of stable KTR (n = 555), higher plasma concentrations of N ε -carboxymethyl-lysine (CML) and N ε -carboxyethyl-lysine (CEL), two advanced glycation end-products (AGEs) of Lys, were associated with higher cardiovascular mortality. Yet, the associations of urinary AGEs with mortality are unknown. In the present study, we measured 24 h urinary excretion of Lys, CML, and furosine in 630 KTR and 41 healthy kidney donors before and after donation. Our result indicate that lower urinary CML and lower furosine excretion rates are associated with higher mortality in KTR, thus resembling the associations of ADMA. Lower furosine excretion rates were also associated with higher cardiovascular mortality. The 24 h urinary excretion rate of amino acids and their metabolites decreased post-donation (varying as little as - 24% for CEL, and as much as - 62% for ADMA). For most amino acids, the excretion rate was lower in KTR than in donors pre-donation [except for S-(1-carboxyethyl)-L-cysteine (CEC) and N G -carboxyethylarginine (CEA)]. Simultaneous GC-MS measurement of free amino acids, their PTM metabolites and AGEs in urine is a non-invasive approach in kidney transplantation., (© 2021. The Author(s).)

Background and Aims: This study aims to investigate the relationship of serum and dietary advanced glycation endproducts (AGEs) with cardiac function and structure after eight years of follow-up., Methods and Results: We included 370 Hoorn Study participants (aged 66.4 ± 6.1, 47% women). Serum protein-bound AGEs [N ε -(carboxymethyl)lysine, N ε -(carboxyethyl)lysine, and pentosidine], as well as echocardiography to assess left atrium volume index (LAVI), left ventricle ejection fraction (LVEF), and left ventricle mass index (LVMI), were measured at baseline and after 8 years of follow-up. Dietary AGEs [N ε -(carboxymethyl)lysine and N ε -(carboxyethyl)lysine] were estimated at baseline with a validated food-frequency questionnaire and an AGEs database. Increased pentosidine [-1.4% (-2.6;-0.2)] and overall serum AGEs Z-scores over time [-2.1% (-3.8;-0.5)] were associated with decreased LVEF at follow-up, adjusted for confounders. Glucose metabolism status was an effect modifier (P-for-interaction = 0.04). In participants with impaired glucose metabolism, but not type 2 diabetes, increased pentosidine was associated with decreased LVEF [-4.2 (-8.0;-0.3)%]. Higher dietary N ε -(carboxyethyl)lysine [1.9 (0.1; 3.7)%] and overall dietary AGEs Z-scores [2.1 (0.1; 4.2)%] were associated with higher LVEF at follow-up. However, prior cardiovascular disease (CVD) was an effect modifier (P = 0.02). We found a stronger, non-significant, association of higher dietary (carboxyethyl)lysine with higher LVEF at follow-up in participants without CVD [2.3 (-0.1; 4.7)%] compared to participants with CVD [0.6 (-2.1; 3.4)%]., Conclusion: Overall serum AGEs were longitudinally associated with impaired systolic function. Future research should focus on including changes in dietary AGEs intake over time and the relation of dietary AGEs with cardiac measures needs to be established in intervention studies using low AGEs diets., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Excessive intake of fructose, glucose and alcohol is associated with the development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). At the same time, these dietetic factors create an environment favorable for the generation of advanced glycation end-products. For this reason, advanced glycation end-products (AGEs) are hypothesized to play role in the development of NAFLD and ALD. In this systematic review and meta-analysis, we explore the relationship between NAFLD and ALD with AGE levels, including their diagnostic accuracy., Methods: The systematic review and meta-analysis has been pre-registered with PROSPERO (CRD42021240954) and was performed in accordance with the PRISMA guidelines. Meta-analyses were performed using the meta R package., Results: We have obtained 11 studies meeting our inclusion criteria, reporting data on 1844 participants (909 with NAFLD, 169 with ALD and 766 healthy controls). NAFLD was associated with significantly higher AGE fluorescence and serum N-(carboxyethyl)lysine (CEL) levels. Patients with alcoholic cirrhosis had significantly higher levels of N-(carboxymethyl)lysine (CML). Only individual studies examined AGEs in the context of their diagnostic accuracy. AGE fluorescence distinguished low and moderate steatosis with an AUC of 0.76. The ratio of CML, CEL and pentosidine to a soluble variant of the AGE receptor differentiated patients with NAFLD from healthy controls with high AUC (0.83-0.85). Glyceraldehyde-derived AGE separated non-alcoholic fatty liver (NAFL) from non-alcoholic steatohepatitis (NASH) with acceptable performance (AUC 0.78)., Conclusions: In conclusion, NAFLD and ALD are associated with significantly higher levels of several AGEs. More research is needed to examine the diagnostic accuracy of AGEs, however individual studies show that AGEs perform well in distinguishing NAFL from NASH.

Scope: Increased consumption of modern processed foods rich in AGEs is drawing worldwide concerns because they are related with rising diabetes prevalence. This study aimed to investigate if pterostilbene (PTE) regulates glucose metabolism and insulin signaling, as well as its potential mechanism in the context of AGEs exposure., Methods and Results: In vitro, Lo2 and HepG2 cells are treated with vehicle, AGEs with or without PTE. AGEs exposure directly impair insulin action as evidenced by assays of insulin-stimulated glucose uptake, consumption, and output. However, PTE efficiently rescue the AGE-induced phenotypes in both cell lines, and enhance IRS-1/PI3K/AKT insulin signaling in a dose-dependent manner. In vivo, C57BL6 mice are fed with regular, high AGEs diet and high AGEs plus PTE. PTE administration effectively improves hyperglycemia, glucose tolerance, and impaired hepatic insulin signaling induced by AGEs, consistent with the in vitro experiments. Moreover, PTE reduce AGEs accumulation in liver and serum. RNA-seq data indicate that PTE counteracts several AGEs-induced dysfunctions including diabetes related process, glucose metabolic process, immune response, and so on., Conclusion: PTE treatment prominently reduced AGEs accumulation and alleviated AGEs-associated diabetes symptoms. PTE could be used as a promising glucose-sensitizing agent for nutritional intervention., (© 2021 Wiley-VCH GmbH.)

Background: Circulating levels of soluble receptor for advanced glycation end products (sRAGE) and advanced glycation end products (AGEs) correlate with aging/cardiovascular risk, which is delayed in long-living individuals (LLIs). AGEs/sRAGE isoforms (cleaved RAGE [cRAGE] and secretory RAGE [esRAGE]) ratio is a valuable marker for disease risk. Results: We evaluated circulating sRAGE isoforms, and AGEs in LLIs (n = 95; 90-105 years) and controls (n = 94; 11-89 years). cRAGE decreased with age in controls and further declined in LLIs. esRAGE increased in LLIs. AGEs rose with age in controls and decreased in LLIs that were characterized by a lower AGEs/sRAGE ratio. Notably, cRAGE and AGE/esRAGE ratio better discriminated controls from LLIs. Conclusion: circulating cRAGE could be considered a reliable marker of chronological age while esRAGE a protective factor for longevity.

Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls ( p < 0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49 ± 4.7 vs. 67.93 ± 8.8, p < 0.001), AOPP (137.64 ± 21.9 vs. 119.08 ± 33.1, p < 0.001), MDA (3.56 ± 0.30 vs. 3.05 ± 0.33, p < 0.001), and ox-LDL (19.78 ± 0.97 vs. 16.94 ± 1.02, p < 0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL ( d = -2.853, 95% CI 2.50-3.19) and MDA ( d = -1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5 ± 156.7 vs. 1239.3 ± 290, p < 0.001) and CAT (2.34 ± 0.34 vs. 2.63 ± 0.38, p < 0.001), GPx (102.37 ± 6.58 vs. 108.03 ± 6.95, p < 0.001), and SOD (5.13 ± 0.39 vs. 5.53 ± 0.31, p < 0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD ( d = 1.135, 95% CI 0.46-0.34) and GPx ( d = 0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Salome Sadat Salehi et al.)

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.

Background Diabetes has a pronounced effect on the peripheral vasculature. The accumulation of advanced glycation end products (AGEs) is regarded as the crucial mechanism responsible for vascular damage in diabetes, but it is not easy to be avoided from food. In this study, we aimed to investigate the effects of an oral absorbent, AST-120, on the accumulation of AGEs and changes in blood flow recovery in diabetic mice. Methods The mice were divided into four groups, wild-type (WT) mice without treatment, WT mice treated with 5% AST-120 mixed into pulverized chow, streptozotocin-induced diabetes mellitus (DM) mice, and DM mice treated with 5% AST-120. Six weeks after hind-limb ischemia surgery, blood flow reperfusion, histology, plasma AGE, and cytokine were examined. Bone marrow cells were cultured and derived into macrophages to evaluate the effects of AGEs on macrophage polarization. Results Plasma AGEs were significantly increased in diabetic mice. AST-120 could bind to AGEs and reduced their plasma concentrations. Histological analysis revealed fewer collateral vessels with corresponding impairment of blood flow recovery in diabetic mice. In these mice, AGE-positive and AGE receptor-positive macrophages were numerous in ischemic limbs compared with non- diabetic mice. In diabetic mice, macrophages in ischemic tissues demonstrated greater M1 polarization than M2 polarization; this pattern was reversed in the AST-120 treatment group. The change in macrophage polarization was associated with the corresponding expression of pro-inflammatory cytokines in the ischemic tissues. In cell cultures, AGEs triggered the transformation of bone marrow-derived macrophages into the M1 phenotype. The alterations in the polarization of macrophages were reversed after treatment with AST-120. Conclusions Oral administration of AST-120 decreased the serum levels of AGEs in diabetic mice and improved neovascularization of ischemic limbs. This benefit may be due to, at least partially, the alterations in macrophage polarization and the associated changes in inflammatory cytokines., (Copyright © 2021. Published by Elsevier Ltd.)

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs-Nε-(carboxy-methyl)lysine (CML), Nε-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)-were measured by ultra-performance liquid chromatography-tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27-0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53-1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37-0.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The aim of this study was to determine whether advanced glycation end products (AGEs) revealed by skin autofluorescence (SAF), serum and urine pentosidine level, and serum homocysteine level can serve as a biomarker for sarcopenia in older women. The participants were 70 elderly women. The AGEs pentosidine, homocysteine, and SAF were measured as aging markers. This study shows that among the biomarkers for aging, serum pentosidine correlates with a loss of appendicular lean mass and can serve as a biomarker for sarcopenia. Moreover, SAF and homocysteine values exhibited a positive correlation with age and correlated with each other. Abbreviations : AGEs: advanced glycation end products; BIA: bioelectrical impedance analyzer; BMD: bone mineral density; DLS: degenerative lumbar scoliosis; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunoassay; HHcy: hyperhomocysteinemia; RIA: radioimmunoassay; SAF: skin autofluorescence; SMI: skeletal muscle mass index; T2DM: type 2 diabetes patients.

This work explored influences of protocatechuic acid (PCA) on type 2 diabetes (T2D)-associated hepatic insulin resistance and other metabolic, hepatic and vascular irregularities using the rat model of high fat diet (HFD)+high fructose+low dose streptozotocin (STZ). Twenty-four male Wister rats were used. Twelve rats were ad libitum supplied with HFD and high fructose drinking water (25 % w/v) for 60 days. On day 30, they received a single injection of STZ (35 mg/kg, i.p). On day 32, they were divided into two subgroups (n = 6/each): T2D + PCA, received PCA (100 mg/kg/day, orally) and T2D, received PCA vehicle till the end of experiment. Rats provided with regular diet and fructose-free drinking water, with or without PCA treatment, served as PCA and control groups (n = 6/each), respectively. PCA treatment significantly reduced the elevated levels of fasting glycemia and insulin, AUC OGTT , AUC ITT , and HOMA-IR index, while it boosted HOMA-β and insulinogenic index values in T2D rats. PCA ameliorated serum lipid levels and hepatic function parameters and mitigated hepatosteatosis in T2D rats. Mechanistically, PCA mitigated hepatic lipid peroxidation and restored reduced glutathione (GSH) and superoxide dismutase (SOD) to near-normal levels. Moreover, PCA enhanced hepatic protein levels of P-AKT ser473 and hepatic mRNA expression of insulin receptor substrate 1 (IRS1), phosphatidylinositol 3 kinase (PI3K)-p85 and AKT2. Furthermore, PCA ameliorated aortic oxidative stress in T2D rats, possibly via reducing serum levels of advanced glycation end products (AGEs) and diminishing vascular expression of RAGE and NOX4 mRNA. Collectively, PCA may improve hepatic insulin resistance and vascular oxidative status by modulating IRS1/PI3K/AKT2 and AGE-RAGE-NOX4 pathways, respectively., (Copyright © 2020. Published by Elsevier B.V.)

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of β2-microglobulin (β2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of β2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated β2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of β2M were not statistically different ( p > 0.35). Dialytic elimination of MM uremic toxin β2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.