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Purpose: To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. Materials and Methods: This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community-dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. Results: The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Conclusions: Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels. [ABSTRACT FROM AUTHOR]

Abstract Diabetes mellitus and arterial hypertension are among the five risk factors that increase mortality in the world. Both are chronic, non-communicable diseases (NCDs), that have a pathophysiological association. Advanced glycation end products (AGEs), produced by the lack of glycemic control in diabetic patients, interact with their AGE receptors (AGER) resulting in increased arterial stiffness, inflammation and endothelial changes - which increases the risk of developing hypertension and other complications. We ran a systematic review in Pubmed, SciELO, Cochrane Library and Web of Science databases using keywords and Boolean operators to optimize the search, with the objective of assessing the mechanism of non-enzymatic glycation of proteins present in patients with diabetes and its correlation with the onset of hypertension, exposing all the endothelial and cellular damage caused by AGEs. We found 719 papers, of which 99 were read in full, and 26 met the eligibility criteria and were included in the present review. AGEs should be considered one of the main cardiometabolic risk factors. Reducing the AGE-AGER interaction will result in cardiovascular protection and increased life expectancy.

Phenolic compounds have antiglycation activity, but the changes occurring during thermal treatment (TT) in these activities are not completely understood. The effects of the extraction conditions of (poly)phenols from Ribes magellanicum fruits, before and after TT, on their antioxidant and antiglycation effects were assessed. (Poly)phenol-enriched extracts (PEEs) from raw and TT (90 °C, 1 h) Ribes magellanicum were extracted using three solvent mixtures (ethanol/water/acetic acid) with increasing water content (0, 24, and 49%) and three solvent-to-solid ratios (5, 10, and 20 mL/g). PEEs of raw samples showed increased values of total (poly)phenols (TPC), TEAC, and FRAP and decreased IC 50 values of fluorescent advanced glycation end products (AGEs) with increasing water content. An increase in TPC and FRAP values was observed for TT samples, but an increase in the IC 50 values of fluorescent AGEs for PEEs with increasing water content was observed. Antiglycation activity (IC 50 raw/IC 50 TT) depended on the solvent-to-solid ratio and the extracting solvent. HPLC-DAD-MS analysis of raw and TT samples showed degradation of anthocyanins, flavonoid fragmentation, and oxidation as the main changes in the phenolic composition of TT samples. We show that TT affects the (poly)phenolic composition of R. magellanicum , producing a decrease in the antiglycation activity when extractions are performed with increasing water content, despite increasing TPC and FRAP activity.

Quantifying glycated albumin (GA) levels in the blood is crucial for diagnosing diabetes because they strongly correlate with blood glucose concentration. In this study, a biotic/abiotic sandwich assay was developed for the facile, rapid, and susceptible detection of human serum albumin (HSA) and GA. The proposed sandwich detection system was assembled using a combination of two synthetic polymer receptors and natural antibodies. Molecularly imprinted polymer nanogels (MIP-NGs) for HSA (HSA-MIP-NGs) were used to mimic capture antibodies, whereas antibodies for HSA or GA were used as primary antibodies and fluorescent signaling MIP-NGs for the Fc domain of IgG (F-Fc-MIP-NGs) were used as a secondary antibody mimic to indicate the binding events. The HSA/anti-HSA/F-Fc-MIP-NGs complex, formed by incubating HSA and anti-HSA antibodies with F-Fc-MIP-NGs, was captured by HSA-MIP-NGs immobilized on the chips for fluorescence measurements. The analysis time was less than 30 min, and the limit of detection was 15 pM. After changing the anti-HSA to anti-GA (monoclonal antibody), the fluorescence response toward GA exceeded that of HSA, indicating successful GA detection using the proposed sandwich detection system. Therefore, the proposed system could change the detection property by changing a primary antibody, indicating that this system can be applied to various target proteins and, especially, be a powerful approach for facile and rapid analysis methods for proteins with structural similarity., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), and fructosamine have attracted considerable interest as markers of hyperglycemia. This study aimed to evaluate the optimal cutoff values for GA, 1,5-AG, and fructosamine and to determine their respective diagnostic efficacies in relation to hyperglycemia., Methods: We enrolled 6012 individuals who had undergone fasting blood glucose (FBG) and Hemoglobin A1c (HbA1c) tests along with at least one alternative glycemic marker. Receiver operating characteristic (ROC) curves and the upper or lower limit of the reference range (97.5 or 2.5 percentiles) were used to ascertain the optimal cutoff values. Follow-up data from healthy individuals were used to identify patients who developed diabetes mellitus (DM)., Results: The ROC cutoff values for GA, 1,5-AG, and fructosamine were 13.9%, 13.3 μg/mL, and 278 μmol/L, respectively, with corresponding area under the curve (AUC) values of 0.860, 0.879, and 0.834. The upper limits of the reference intervals for GA and fructosamine were 15.1% and 279 μmol/L, respectively, and the lower limit for 1,5-AG was 5.3 μg/mL. Among the GA cutoff values, the ROC cutoff had the highest sensitivity. Analyzing the follow-up data showed that lowering the GA cutoff from 16.0% to 13.9% identified an additional 40 people with DM progression., Conclusions: Lowering the GA cutoff values significantly increased the sensitivity of DM diagnosis and enhanced its potential as a screening marker by identifying more individuals with diabetes progression. Conversely, modifications to the cutoff values for 1,5-AG and fructosamine did not confer any discernible diagnostic or predictive advantages., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Dietary advanced glycation end products (AGEs) may promote oxidative stress and inflammation in the gastrointestinal tract., Aims: The aim of this study is to investigate the association between dietary AGE intake and the risk of inflammatory bowel disease (IBD)., Methods: We included 121,978 participants without IBD at baseline from the UK Biobank. We estimated consumption of three common AGEs (Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) by matching 24-h dietary questionnaires to a validated dietary AGE database. We used Cox proportional hazards regression models to calculate the hazard ratio (HR) and 95% CI of the association between dietary AGEs and IBD risk., Results: During a median follow-up of 13.72 years, 671 participants developed IBD (192 with Crohn's disease (CD) and 478 with ulcerative colitis (UC)). Among the assessed dietary AGEs, only CEL was associated with an increased risk of IBD (HR = 1.09, 95% CI: 1.01-1.18, p = 0.020) and CD (HR = 1.18, 95% CI: 1.03-1.36, p = 0.014), particularly for participants who were overweight, physically inactive, and non-smokers. Among participants at a high genetic risk of CD, HRs (95% CI) of CD were 1.26 (1.00-1.57) for CML, 1.41 (1.12-1.77) for CEL, and 1.28 (1.01-1.62) for MG-H1 (p < 0.05 for each). However, none of the dietary AGEs was significantly associated with UC risk, irrespective of genetic predisposition., Conclusions: Dietary CEL was associated with an increased risk of IBD and CD, but not UC. Further interventional studies are required to support the potential benefit of AGE restriction, especially for individuals at a high genetic risk of CD., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Aims/introduction: Diabetes mellitus is a traditional risk factor for heart failure (HF), and glycated albumin (GA) is a marker to assess short-term glycemic control. Whether GA has prognostic significance in patients with HF remains unclear., Materials and Methods: A total of 717 patients with HF were enrolled in the prospective cohort study. Patients were grouped by the normal upper limit of GA (17%). Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the association between GA and prognosis., Results: During a mean follow-up of 387 days, 232 composite endpoint events of hospitalization for HF or all-cause death occurred. Kaplan-Meier analysis showed a higher rate of adverse events in the higher GA group (GA >17%; log-rank test P < 0.001). GA was an independent predictor of adverse events, both as a continuous variable (per 1% change: hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00-1.06, P = 0.030) and as a categorical variable (GA >17%: HR 1.36, 95% CI 1.03-1.80, P = 0.032). Restricted cubic splines showed a linear association between GA and adverse events (P for non-linearity = 0.231). There was no significant difference in adverse outcome risk between those with diabetes and GA ≤17% and those without diabetes, whereas the prognosis was worse in those with diabetes and GA >17% (HR 1.56, 95% CI 1.16-2.11, P = 0.004). Compared to the group with normal levels of GA and glycated hemoglobin, the group with GA >17% and glycated hemoglobin >6.5% had a higher risk of adverse events (HR 1.49, 95% CI 1.06-2.10, P = 0.022)., Conclusions: GA was an independent predictor of HF prognosis. Combining GA and glycated hemoglobin might improve the predictive power of adverse outcomes in patients with HF., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To explore the diagnostic value of glycated CD59 (gCD59) in gestational diabetes mellitus (GDM)., Methods: A total of 707 pregnant women who underwent the first visit in the obstetric outpatient clinic of the Affliated Suqian Hospital of Xuzhou Medical University from January 2022 to July 2023 were included, and were grouped according to the International Association of the Diabetes and Pregnancy Study Groups(IADPSG) diagnostic criteria, and finally 113 cases in the GDM group and 559 cases in the normal glucose tolerance (NGT) group were included, and the concentration of gCD59 was determined by enzyme-linked immunosorbent assay (ELISA). The baseline data characteristics of the two groups were compared, the risk factors for GDM were explored by multivariate binary logistic analysis, and the diagnostic value of gCD59 in predicting GDM was explored by receiver operating characteristic (ROC) curve analysis., Results: The level of gCD59 in the GDM group was significantly higher than that in the NGT group (1.49 SPU vs 0.87 SPU). Multivariate regression analysis showed that gCD59, diastolic blood pressure (DBP) and thyroid stimulating hormone (TSH) were independent risk factors for GDM.The area under the curve (AUC) of gCD59 for the diagnosis of GDM was 0.681 (95% CI : 0.583-0.717), with a sensitivity of 71.7% and a specificity of 58.3%. In combination with fasting glucose, gCD59 effectively diagnosed GDM with higher AUC of 0.871 (95% CI : 0.708-1.000)., Conclusion: gCD59 is an independent risk factor for GDM and a good biomarker for the diagnosis of GDM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Xu, Lu, Cao, Zuo, Zhang, Zou and Sun.)

The burden of diabetes is rising in developing countries, and this is significantly linked to the increasing prevalence of poor glycemic control. The cost of glycated haemoglobin (HbA1c) testing is a barrier to timely glycemic assessments, but newer tests such as glycated albumin may be cheaper and tempting alternatives. Additional research must ascertain if glycated albumin (GA) can act as a viable supplement or alternative to conventional HbA1c measurements for glycemic control in diabetic individuals. GA as a biomarker is an emerging area of interest, particularly for those who display unreliable HbA1c levels or cannot afford the test. This study aims to investigate the prevalence of poor glycemic control in outpatient diabetic patients and the utility of glycated albumin in this population's monitoring of glycemic control. Method. A cross-sectional study of 203 diabetic patients will be conducted at the Dodoma Regional Referral Hospital and Benjamin Mkapa Hospital from August 1st, 2023, to August 31st, 2024. Patients diagnosed with diabetes mellitus for over six months will be screened for eligibility. Informed consent, history, clinical examination, and voluntary blood sample collection will be obtained from all eligible patients. Glycated Albumin levels will be obtained from the same blood samples collected. The glycemic status of all patients will be defined as per HbA1c, and a level of greater than 7% will considered as a poor control. The analysis will be computed with SPSS version 28.0, and a predictor variable, P<0.05, will be regarded as statistically significant, with the utility of GA determined by plotting the area under the ROC curve and the confusion matrix., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mkumbi, Boaz. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), acrylamide (AA), 5-hydroxymethylfurfural (5-HMF), and polycyclic aromatic hydrocarbons (PAHs) are toxic substances that are produced in certain foods during thermal processing by using common high-temperature unit operations such as frying, baking, roasting, grill cooking, extrusion, among others. Understanding the formation pathways of these potential risk factors, which can cause cancer or contribute to the development of many chronic diseases in humans, is crucial for reducing their occurrence in thermally processed foods. During thermal processing, food rich in carbohydrates, proteins, and lipids undergoes a crucial Maillard reaction, leading to the production of highly active carbonyl compounds. These compounds then react with other substances to form harmful substances, which ultimately affect negatively the health of the human body. Although these toxic compounds differ in various forms of formation, they all partake in the common Maillard pathway. This review primarily summarizes the occurrence, formation pathways, and reduction measures of common toxic compounds during the thermal processing of food, based on independent studies for each specific contaminant in its corresponding food matrix. Finally, it provides several approaches for the simultaneous reduction of multiple toxic compounds., 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. Published by Elsevier Inc.)

Abstract Background Rubeosis faciei diabeticorum is a persistent facial erythema in patients with diabetes mellitus. The actual pathogenesis has not been studied. However, it is speculated to be a cutaneous diabetic microangiopathy. Objective Examine the correlation between the severity of facial erythema and the possible causes of microvascular diabetic complications, namely oxidative stress, hyperglycemia, and cutaneous accumulation of advanced glycation end-products . Methods Patients diagnosed with Type 2 diabetes mellitus (n = 32) were enrolled in the study. The facial erythema index was measured using the Mexameter MX18; cutaneous accumulation of advanced glycation end-products was estimated by measuring skin auto fluorescence with the AGE Reader (DiagnOptics Technologies B.V. - Groningen, Netherlands). Glycated haemoglobin, total antioxidant status, and malondialdehyde were measured in blood by TBARS assay. The correlation between the selected variables was assessed by Spearman's rank test; p ≤ 0.05 was considered statistically significant. Results There was a statistically significant correlation between total antioxidant status and the facial erythema index (ρ = 0.398, p = 0.024). Malondialdehyde, skin autofluorescence, glycated haemoglobin, body mass index, duration of diabetes, and age did not demonstrate statistically significant correlation with the facial erythema index. Study limitations This is an observational study. Elevation of total antioxidant status could have been caused by several factors that might have also influenced the development of rubeosis faciei, including hyperbilirubinemia and hyperuricemia. Conclusions The results contradicted expectations. Total antioxidant status correlated positively with facial erythema index; however, there was no correlation with oxidative stress and skin autofluorescence. Further investigations should be conducted to reveal the cause of total antioxidant status elevation in patients with rubeosis faciei.

Background: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS)., Methods: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%)., Results: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c., Conclusions: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c., (© 2024. The Author(s).)

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF's association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D)., Materials and Methods: A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation., Results: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], p = 0.001)., Conclusion: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263 095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

As accumulated evidence suggests that individuals with post-traumatic stress disorder (PTSD) encounter earlier and more frequent occurrences of cardiovascular diseases, the aim of this study was to ascertain the differences in lifestyle and cardiovascular risk between PTSD and complex PTSD patients. We enrolled 137 male war veterans with PTSD (89 had complex PTSD). The diagnosis was established based on 11th revision of International Classification of Diseases (ICD-11), and cardiovascular risk was estimated by the measurement of advanced glycation end products. Adherence to Mediterranean diet (MD) was lower in the complex PTSD group (2.2% vs. 12.5%, p = 0.015). Accordingly, patients with complex PTSD had lower healthy lifestyle scores in comparison to PTSD counterparts (50.6 ± 9.7 vs. 59.6 ± 10.1, p < 0.001), and a positive association was noted between MD adherence and a healthy lifestyle (r = 0.183, p = 0.022). On the other hand, differences were not noted in terms of physical activity ( p = 0.424), fat % ( p = 0.571) or cardiovascular risk ( p = 0.573). Although complex PTSD patients exhibit worse adherence to MD and lower healthy lifestyle scores, these differences do not seem to impact physical activity, body composition, or estimated cardiovascular risk. More research is needed to clarify if this lack of association accurately reflects the state of the PTSD population or results from insufficient statistical power.

In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.

Diabetic kidney disease (DKD) is the major cause of end-stage kidney disease. However, only renin-angiotensin system inhibitor with multidisciplinary treatments is effective for DKD. In 2019, sodium-glucose cotransporter 2 (SGLT2) inhibitor showed efficacy against DKD in Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, adding a new treatment option. However, the progression of DKD has not been completely controlled. The patients with transient exposure to hyperglycemia develop diabetic complications, including DKD, even after normalization of their blood glucose. Temporary hyperglycemia causes advanced glycation end product (AGE) accumulations and epigenetic changes as metabolic memory. The drugs that improve metabolic memory are awaited, and AGE inhibitors and histone modification inhibitors are the focus of clinical and basic research. In addition, incretin-related drugs showed a renoprotective ability in many clinical trials, and these trials with renal outcome as their primary endpoint are currently ongoing. Hypoxia-inducible factor prolyl hydroxylase inhibitors recently approved for renal anemia may be renoprotective since they improve tubulointerstitial hypoxia. Furthermore, NF-E2-related factor 2 activators improved the glomerular filtration rate of DKD patients in Bardoxolone Methyl Treatment: Renal Function in chronic kidney disease/Type 2 Diabetes (BEAM) trial and Phase II Study of Bardoxolone Methyl in Patients with Chronic Kidney Disease and Type 2 Diabetes (TSUBAKI) trial. Thus, following SGLT2 inhibitor, numerous novel drugs could be utilized in treating DKD. Future studies are expected to provide new insights. [ABSTRACT FROM AUTHOR]

Glycated albumin (GA), defined as the percentage of serum albumin glycation, is a mid-term glycemic control marker for diabetes. The concentrations of both glycated human serum albumin (GHSA) and total human serum albumin (HSA) are required to calculate GA. Here, we report the development of a GA sensor employing two albumin aptamers: anti-GHSA aptamer which is specific to GHSA and anti-HSA aptamer which recognizes both glycated and non-glycated HSA. We combine these aptamers with extended gate field effect transistors (EGFETs) to realize GA monitoring without the need to pretreat serum samples, and therefore suitable for point of care and home-testing applications. Using anti-GHSA aptamer-immobilized electrodes and EGFETs, we measured GHSA concentrations between 0.1-10 μM within 20 min. The sensor was able to measure GHSA concentration in the presence of BSA for a range of known GA levels (5-29%). With anti-HSA aptamer-immobilized electrodes and EGFETs, we measured total HSA concentrations from 1-17 μM. Furthermore, GHSA and total HSA concentrations of both healthy and diabetic-level samples were determined with GHSA and HSA sensors. The measured GHSA and total HSA concentrations in three samples were used to determine respective GA percentages, and our calculations agreed with GA levels determined by reference methods. Thus, we developed simple and rapid dual aptamer-based EGFET sensors to monitor GA through measuring GHSA and total HSA concentration, without the need for sample pretreatment, a mandatory step in the current standard of enzymatic GA monitoring., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Koji Sode reports financial support was provided by University of North Carolina and NC State University Joint Department of Biomedical Engineering. Spyridon Pavlidis reports financial support was provided by the National Science Foundation. Mika Hatada reports financial support was provided by The Uehara Memorial Foundation. The authors declare no other competing interests. If there are other authors, they 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. Published by Elsevier B.V.)

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were ≥41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid β-protein (Aβ) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects. In 16% of the subjects, HPτ was limited to the locus coeruleus. In 14 subjects (<1%), no altered proteins were observed. In 3 subjects, only Aβ was observed, and in 17, HPτ was observed in a distribution other than that seen in ADNC/PART. The transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant age-related TDP encephalopathy (LATE) was observed in 565 (35%) subjects and α-synuclein (αS) pathology, i.e., Lewy body disease (LBD) or multi system atrophy (MSA) was observed in the brains of 21% of the subjects. A total of 39% of subjects with ADNC, 59% of subjects with PART, and 81% of subjects with HPτ limited to the locus coeruleus lacked concomitant pathologies, i.e., LATE-NC or LBD-NC. Of the 293 (18% of the 1610 subjects) subjects with dementia, 81% exhibited a high or intermediate level of ADNC. In 84% of all individuals with dementia, various degrees of concomitant alterations were observed; i.e., MIXED-NC was a common cause of dementia. A high or intermediate level of PART was observed in 10 subjects with dementia (3%), i.e., tangle-predominant dementia. No subjects exhibited only vascular NC (VNC), but in 17 subjects, severe VNC might have contributed to cognitive decline. Age-related tau astrogliopathy (ARTAG) was observed in 37% of the 1610 subjects and in 53% of those with dementia.

Diabetes mellitus is recognized as a major predisposing factor for Moraxella keratitis. However, how diabetes mellitus contributes to Moraxella keratitis remains unclear. In this study, we examined Moraxella keratitis; based on the findings, we investigated the impact of advanced glycation end products (AGEs) deposition in the cornea of individuals with diabetic mellitus on the adhesion of Moraxella isolates to the cornea. A retrospective analysis of 27 culture-proven cases of Moraxella keratitis at Ehime University Hospital (March 2006 to February 2022) was performed. Moraxella isolates were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Among the patients, 30.4% had diabetes mellitus and 22.2% had the predominant ocular condition of using steroid eye drops. The species identified were Moraxella nonliquefaciens in 59.3% and Moraxella lacunata in 40.7% of patients. To investigate the underlying mechanisms, we assessed the effects of M. nonliquefaciens adherence to simian virus 40-immortalized human corneal epithelial cells (HCECs) with or without AGEs. The results demonstrated the number of M. nonliquefaciens adhering to HCECs was significantly increased by adding AGEs compared with that in controls (p < 0.01). Furthermore, in the corneas of streptozotocin-induced diabetic C57BL/6 mice treated with or without pyridoxamine, an AGE inhibitor, the number of M. nonliquefaciens adhering to the corneas of diabetic mice was significantly reduced by pyridoxamine treatment (p < 0.05). In conclusion, the development of Moraxella keratitis may be significantly influenced by the deposition of AGEs on the corneal epithelium of patients with diabetes mellitus., (© 2024. The Author(s).)

Aims: Cyclophilin A (CyPA) induces leucocyte recruitment and platelet activation upon release into the extracellular space. Extracellular CyPA therefore plays a critical role in immuno-inflammatory responses in tissue injury and thrombosis upon platelet activation. To date, CD147 (EMMPRIN) has been described as the primary receptor mediating extracellular effects of CyPA in platelets and leucocytes. The receptor for advanced glycation end products (RAGE) shares inflammatory and prothrombotic properties and has also been found to have similar ligands as CD147. In this study, we investigated the role of RAGE as a previously unknown interaction partner for CyPA., Methods and Results: Confocal imaging, proximity ligation, co-immunoprecipitation, and atomic force microscopy were performed and demonstrated an interaction of CyPA with RAGE on the cell surface. Static and dynamic cell adhesion and chemotaxis assays towards extracellular CyPA using human leucocytes and leucocytes from RAGE-deficient Ager-/- mice were conducted. Inhibition of RAGE abrogated CyPA-induced effects on leucocyte adhesion and chemotaxis in vitro. Accordingly, Ager-/- mice showed reduced leucocyte recruitment and endothelial adhesion towards CyPA in vivo. In wild-type mice, we observed a downregulation of RAGE on leucocytes when endogenous extracellular CyPA was reduced. We furthermore evaluated the role of RAGE for platelet activation and thrombus formation upon CyPA stimulation. CyPA-induced activation of platelets was found to be dependent on RAGE, as inhibition of RAGE, as well as platelets from Ager-/- mice showed a diminished activation and thrombus formation upon CyPA stimulation. CyPA-induced signalling through RAGE was found to involve central signalling pathways including the adaptor protein MyD88, intracellular Ca2+ signalling, and NF-κB activation., Conclusion: We propose RAGE as a hitherto unknown receptor for CyPA mediating leucocyte as well as platelet activation. The CyPA-RAGE interaction thus represents a novel mechanism in thrombo-inflammation., Competing Interests: Conflict of interest: D.H. received compensation for travel expenses and participation fees from Abbott and speaker fees from Pfizer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Given the rising prevalence of high fasting plasma glucose (HFPG) over the past three decades, it is crucial to assess its global, national, and regional impact on chronic kidney disease (CKD). This study aims to investigate the burden of CKD attributed to HFPG and its distribution across various levels., Methods and Materials: The data for this research was sourced from the Global Burden of Diseases Study 2019. To estimate the burden of CKD attributed to HFPG, we utilized DisMod-MR 2.1, a Bayesian meta-regression tool. The burden was measured using age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate. Correlation analysis was performed using the Spearman rank order correlation method. Temporal trends were analyzed by estimating the estimated annual percentage change (EAPC)., Results: Globally in 2019, there were a total of 487.97 thousand deaths and 13,093.42 thousand DALYs attributed to CKD attributed to HFPG, which represent a substantial increase of 153.8% and 120%, respectively, compared to 1990. Over the period from 1990 to 2019, the burden of CKD attributable to HFPG increased across all regions, with the highest increases observed in regions with high socio-demographic index (SDI) and middle SDI. Regions with lower SDI exhibited higher ASMR and age-standardized DALYs (ASDR) compared to developed nations at the regional level. Additionally, the EAPC values, which indicate the rate of increase, were significantly higher in these regions compared to developed nations. Notably, high-income North America, belonging to the high SDI regions, experienced the greatest increase in both ASMR and ASDR over the past three decades. Furthermore, throughout the years from 1990 to 2019, males bore a greater burden of CKD attributable to HFPG., Conclusion: With an increasing population and changing dietary patterns, the burden of CKD attributed to HFPG is expected to worsen. From 1990 to 2019, males and developing regions have experienced a more significant burden. Notably, the EAPC values for both ASMR and ASDR were higher in males and regions with lower SDI (excluding high-income North America). This emphasizes the pressing requirement for effective interventions to reduce the burden of CKD attributable to HFPG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei, Ren, Li, Qi, Yang and Li.)

The relationship between diabetes mellitus and ocular complications has been extensively studied by many authors. Diabetic keratopathy has already been well characterized and defined as a clinical entity. This review focuses on exploring corneal epithelial changes in diabetic patients, aiming to provide a pragmatic overview of the existing knowledge on this topic. The paper systematically examines alterations in corneal epithelial structure and their impact on diabetic patients. Advanced imaging techniques are also discussed for their role in precise characterization and improved diagnostics. Additionally, the paper explores the mechanisms behind corneal epithelial changes in diabetes, looking at factors such as hyperglycemia, oxidative stress, and Advanced Glycation End-Products. The impact of altered corneal epithelial integrity on barrier function and susceptibility to external issues is considered, addressing potential links to heightened proteolytic enzyme activities and delayed wound healing observed in diabetic individuals. The review also covers the practical implications of corneal epithelial changes, including the association with corneal erosions, persistent epithelial defects, and an increased risk of dry eye syndrome in diabetic patients.

Background: Diabetes has emerged as an important risk factor for COVID-19 adverse outcomes during hospitalization. We investigated whether the measurement of glycated albumin (GA) may be useful in detecting newly diagnosed diabetes during COVID-19 hospitalization., Methods: In this cross-sectional test accuracy study we evaluated HCPA Biobank data and samples from consecutive in-patients, from 30 March 2020 to 20 December 2020. ROC curves were used to analyse the performance of GA to detect newly diagnosed diabetes (patients without a previous diagnosis of diabetes and admission HbA1c ≥6.5%)., Results: A total of 184 adults (age 58.6 ± 16.6years) were enrolled, including 31 with newly diagnosed diabetes. GA presented AUCs of 0.739 (95% CI 0.642-0.948) to detect newly diagnosed diabetes. The GA cut-offs of 19.0% was adequate to identify newly diagnosed diabetes with high specificity (85.0%) but low sensitivity (48.4%)., Conclusions: GA showed good performance to identify newly diagnosed diabetes and may be useful for identifying adults with the condition in COVID-19-related hospitalization., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chume et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC ( p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Aim: This study aimed to investigate whether skin autofluorescence (SAF) is associated with clinical outcomes in patients with coronary artery disease. Advanced glycation end products (AGE) play a crucial role in atherosclerosis. Accumulation of AGE can be measured non-invasively by SAF., Methods: We performed a single-center prospective study of 896 patients with coronary artery disease treated with percutaneous coronary intervention (PCI) between January 2014 and December 2015. SAF was measured before the PCI procedure. The primary endpoint was patient-oriented composite endpoints (POCE) defined as a composite of all-cause death, any myocardial infarction, any stroke, and any revascularization., Results: Patients were significantly older and suffered higher rates of chronic kidney disease (CKD) in the high SAF group. A higher SAF was associated with an increased risk for POCE (HR 1.43; 95% CI 1.19-1.71, p＜0.001) that was mainly driven by any coronary revascularization (HR 1.33; 95% CI 1.08-1.65, p=0.01) including target lesion revascularization (HR 1.41; 95% CI 1.02-1.94, p=0.04). The higher SAF group also experienced worse outcomes in stroke (HR 2.08; 95% CI 1.38-3.15, p=0.001). Multivariate analyses indicated that SAF was an independent predictor of POCE (HR 1.36; 95% CI 1.13-1.63, p=0.001)., Conclusions: SAF as a measure of AGE deposition is independently associated with cardiovascular events amongst patients with coronary artery disease treated with PCI. SAF also predicts the incidence of restenosis and stroke.

Objective: To examine whether patients with different blood glycemic levels undergoing fixed orthodontic therapy demonstrate changes in the biochemical profiles of crevicular fluid and salivary advanced glycation end products (AGEs) and proinflammatory cytokine levels in comparison with nondiabetic healthy subjects., Materials and Methods: Prediabetic subjects, subjects with type 2 diabetes mellitus (T2DM), and subjects without a diabetes mellitus diagnosis undergoing fixed orthodontic therapy with MBT prescription brackets (0.022-inch brackets and 0.019 × 0.025-inch stainless steel archwires) were included in the study. The following clinical periodontal parameters were evaluated: (1) plaque score (PS), (2) probing depth (PD), (3) bleeding on probing (BOP), and (4) clinical attachment loss. Crevicular fluid and saliva specimens were collected during regular orthodontic visits. Salivary and crevicular fluid tumor necrosis factor alpha, interleukin-6, ghrelin, resistin, AGEs, and receptor activator of nuclear factor κΒ ligand were evaluated using a human magnetic Luminex multiplex assay., Results: BOP scores were significantly higher among T2DM subjects (19.2%) than among nondiabetic subjects (11.2%) and prediabetic subjects (15.9%). Comparable values were demonstrated by all three study groups regarding PD scores and PSs. T2DM subjects demonstrated higher scores for gingival crevicular fluid (GCF) chemokines than nondiabetic and prediabetic subjects. A statistically significant difference was found in the levels of AGEs and resistin among the three study groups. The scores revealed for the levels of GCF resistin and AGEs versus periodontal BOP demonstrated a significant positive association by the Pearson correlation test., Conclusions: T2DM patients demonstrated significantly higher levels of GCF resistin and AGEs during fixed orthodontic therapy. Chronic hyperglycemic patients undergoing orthodontic therapy demonstrated a proinflammatory response., (© 2024 by The EH Angle Education and Research Foundation, Inc.)

Background: Currently, limited research is available on the comparative analysis of chronic kidney disease (CKD) incidence and mortality rates between China and the United States. This study aimed to explore the trends in CKD incidence and mortality rates in both countries, as well as make some future predictions., Methods: The data on CKD incidence and mortality in China and the US from 1990 to 2019 were derived from the 2019 Global Burden of Disease database. A Joinpoint regression model was used to analyze temporal trends in CKD incidence and mortality. An age-period-cohort model was used to assess the effects of age, period, and birth cohort on CKD risk and forecast the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of CKD in China and the US over the next 15 years., Results: CKD incidence in China and the US showed an upward trend. Its mortality rate showed a downward trend in China but an upward one in the US. The relative risk (RR) of CKD incidence and mortality increases with age. The RR of CKD incidence in the 0-5 age group exceeds that in the 5-55 age group, and the RR for mortality surpasses that in the 5-35 age group. Over time, the RR of CKD incidence has gradually increased in China and the US. Individuals born in later birth cohorts had a lower RR of CKD incidence and mortality. The ASIR of CKD may increase in both China and the US, whereas its ASMR may decline over the next 15 years., Conclusion: Screening measures should be strengthened among populations at high risk of CKD; prenatal examinations of pregnant women should be emphasized to reduce CKD incidence in newborns. It is imperative to increase health education and encourage individuals to adopt healthy lifestyles., (© 2024. The Author(s).)