Patients with rheumatic diseases suffer depression at a far greater rate than the general population. Aside from evident mental health degradation, in this group of patients depression can often lead to failures in the treatment of the basic disease. The aim of the study was to assess the concentration of advanced glycation end-products (AGE) in the skin autofluorescence (SAF) exam in patients with select rheumatic diseases depending on depression concomitance. 139 patients with rheumatic diseases were enrolled into the study-43 (39F/4 M) patients with RA, 31 (24F/7 M) patients with PsA, 27 (22F/5 M) patients with SLE and 38 (33F/5 M) patients with SSc. In all patients, the concentration of AGE was assessed using the AGE Reader device (DiagnOptics BV Groningen, The Netherlands). The Beck Depression Inventory II was used to assess depression in the patients. Patients who scored 14 points or more in the BDI-II were diagnosed with depression. In the studied group, depression was identified in 73 (53%) patients-25 with RA, 21 with PsA, 11 with SLE and 16 with SSc. Mean SAF in patients with depression was 2.8 ± 0.4, and in the group with no depression-2.2 ± 0.5 (p < 0.001). The study results indicate that in the course of rheumatic diseases, the presence of depression may influence the increase in AGE concentration in the skin. Therefore, evaluating AGE levels in the skin may be clinically relevant as it can help identify patients who may be at risk of developing depression.

α-Dicarbonyls and advanced glycation end products (AGEs) may contribute to the pathogenesis of insulin resistance by a variety of mechanisms. To investigate whether young insulin-resistant subjects present markers of increased dicarbonyl stress, we determined serum α-dicarbonyls-methylglyoxal, glyoxal, 3-deoxyglucosone; their derived free- and protein-bound, and urinary AGEs using the UPLC/MS-MS method; soluble receptors for AGEs (sRAGE), and cardiometabolic risk markers in 142 (49% females) insulin resistant (Quantitative Insulin Sensitivity Check Index (QUICKI) ≤ 0.319) and 167 (47% females) age-, and waist-to-height ratio-matched insulin-sensitive controls aged 16-to-22 years. The between-group comparison was performed using the two-factor (sex, presence/absence of insulin resistance) analysis of variance; multiple regression via the orthogonal projection to latent structures model. In comparison with their insulin-sensitive peers, young healthy insulin-resistant individuals without diabetes manifest alterations throughout the α-dicarbonyls-AGEs-sRAGE axis, dominated by higher 3-deoxyglucosone levels. Variables of α-dicarbonyls-AGEs-sRAGE axis were associated with insulin sensitivity independently from cardiometabolic risk markers, and sex-specifically. Cleaved RAGE associates with QUICKI only in males; while multiple α-dicarbonyls and AGEs independently associate with QUICKI particularly in females, who displayed a more advantageous cardiometabolic profile compared with males. Further studies are needed to elucidate whether interventions alleviating dicarbonyl stress ameliorate insulin resistance.

OBJECTIVE: Acromegaly is associated with oxidative stress and inflammation parameters. Chitotriosidase (CHITO) is a marker of macrophage activation and plays a pivotal role in the activation of inflammatory and immunological responses. Our study aimed to determine CHITO,YKL-40, advanced glycation end product (AGE), and high-sensitivity C-reactive protein (hsCRP) levels to investigate malondialdehyde (MDA), catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities and to evaluate any association of these parameters with carotid intima media thickness (cIMT) in patients with controlled acromegaly.
METHODS: Thirty controlled acromegaly patients and 41 age- and sex-matched control cases were studied. We obtained demographic data, hormonal and metabolic parameters, and cIMT. CHITO activity was measured with the fluorometric method of Chamoles et al. YKL-40 and hsCRP levels were measured using ELISA. AGEs were measured based on spectrofluorimetric detection. GSH-Px activity was determined by a colorimetric assay. MDA, SOD, and catalase activities were determined in hemolysis.
RESULTS: Higher CHITO, AGE, and hsCRP concentrations were observed in patients with acromegaly compared to controls. SOD levels were non-significantly higher in the acromegaly group, while catalase activities were lower in patients with acromegaly. Correlation analyses of CHITO, AGEs, YKL-40, hsCRP, MDA, catalase, GSH-Px, and SOD with metabolic, anthropometric, and laboratory parameters did not demonstrate any significant correlation (p > 0.05). There was no significant difference between groups with regard to cIMT levels.
CONCLUSIONS: This is the first study investigating CHITO and AGE levels in patients with acromegaly. Serum CHITO, AGE, and hsCRP levels in acromegalic patients were significantly increased. It may be important to evaluate CHITO, AGE, and hsCRP levels in acromegalic patients who are already under cardiometabolic surveillance due to risk of developing cardiovascular disease.

Advanced glycation end-products (AGE) are complex compounds formed by nonenzymatic glycosylation of proteins, nucleic acids, and lipids with glucose in the blood. We aimed to investigate whether there was a difference in first-trimester serum AGE levels of pregnant women with and without risk factors for gestational diabetes mellitus (GDM) and their obstetric outcomes. There were 44 women in study group who have risk factors for GDM and 44 as controls. Demographic features, serum AGE levels, adverse perinatal and neonatal outcomes were compared between groups. Five patients (11.4%) in the study group and one patient (2.3%) in the control group were diagnosed as GDM (p = .2). The serum AGE values were not statistically different between the study and control groups. There were no statistical differences between groups in terms of adverse perinatal and neonatal outcomes. However, in the group with adverse perinatal outcome (n = 25), AGE values were higher than the control group. The results of our preliminary study suggested that high-risk women for GDM did not have increased serum levels of AGE in the first trimester. Nevertheless, a high first-trimester serum AGE level was found to be associated with adverse perinatal outcomes. IMPACT STATEMENTWhat is already known on this subject? Advanced glycation end products (AGE) are markers that are associated with diabetes and its complications. For pregnant women, a high third trimester serum AGEs levels were found in women who had gestational diabetes.What do the results of this study add? The results of our study revealed that first trimester screening of serum AGE levels of women who had risk factors for gestational diabetes was not discriminate. Nevertheless, a high first trimester serum AGE levels was associated with adverse perinatal outcome.What are the implications of these findings for clinical practice and/or further research? Whether reducing exogenous sources of AGE (western-style diet, smoking) before pregnancy will be associated with better pregnancy outcomes should be investigated in future studies.

BACKGROUND: Zishen Yutai Pills (ZYP), a famous traditional Chinese patent medicine, has been widely applied to avoid recurrent miscarriage and treat threatened abortion. Polysaccharides of ZYP (ZYPPs) play an essential role in the theraprutic effects of ZYP. However, the complex compositions of ZYP and the complicated structure of ZYPPs have posed great challenges and barriers to the quality evaluation of ZYP.
OBJECTIVE: To identify and characterize the ZYPPs for better quality control of ZYP, a reliable and valid quality control system was established in this study.
METHODS: A multi-fingerprint profile strategy based on HPSEC-MALL-RID, FT-IR, and HPLC (complete acid digested fingerprint, partial acid digested fingerprint and enzymatically digested fingerprint) was established to identify and discriminate the chemical structure of ZYPPs. Besides, the purpose of revealing the relationships between structure and biological activity of ZYPPs, their chemical characteristics, in vitro antioxidant and anti-glycation activities were investigated and discussed.
RESULTS: The similarity evaluation of ZYPPs indicated ZYPPs from different batches showed a high similarity based on the correlation coefficient values of multi-fingerprints. Furthermore, ZYPPs exhibited remarkable antioxidant and antiglycation properties, which might be attributed to their molecular weights and the content of uronic acids.
CONCLUSIONS: These results indicated that the multiple fingerprint technique was reliable and effective for the improvement of quality control of ZYPPs, suggesting the multiple fingerprint technique could also be potentially applied as a valid and feasible strategy to control the quality of polysaccharide-enriched herbal medicines.

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct Nɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed advanced glycation end products (AGEs) are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using methylglyoxal-derived hydroimidazolone 1 (MG-H1) as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

BACKGROUND: Previous studies have suggested that increased levels of advanced glycation end products (AGEs) and soluble receptor for AGE (sRAGE) are associated with diabetes-related complications. However, there is little evidence on the association between long-term levels of AGEs and sRAGE and progression of diabetes-related complications.
UNASSIGNED: A 64-year-old man had poorly controlled type 2 diabetes, obesity, smoking, hypertension, and dyslipidemia. He had many risk factors for diabetes-related complications.
METHODS: Despite poor glycemic control over 15 years, the patient did not exhibit diabetes-related complications.
METHODS: We examined serum AGEs (CEL and MG-H1) and sRAGE levels in this patient over the past 10 years.
RESULTS: The patient maintained low serum AGEs and sRAGE levels.
CONCLUSIONS: AGEs and sRAGE levels may be associated with long-term development of diabetes-related complications.

BACKGROUND: Insulinoma represents hypoglycemia as a predominant symptom; the autonomic symptoms may be resolved by chronically recurrent hypoglycemia resulting in the persistence of non-specific symptoms alone. Therefore, it has been estimated that there are many patients in whom the disease takes longer to diagnose and has remained undiagnosed. Although some parameters exist for the definitive diagnosis of the disease, there are currently no indices for early screening. Indices of glycemic control, hemoglobin A1c (HbA1c), and glycated albumin (GA) may be useful for the screening of patients with insulinoma having chronic hypoglycemia because the values become low in such a condition. Because there are no articles that have reported the point, we examine the effective cutoff values of HbA1c and GA for the diagnosis of insulinoma in the present study.
METHODS: In a multicenter cross-sectional study, 31 patients with insulinoma were included for comparison with 120 control subjects with normal glucose tolerance based on 75 g oral glucose tolerance tests whose characteristics were matched to the patients. The primary outcomes were optimal cutoff values of HbA1c and GA for the screening of insulinoma.
RESULTS: HbA1c was significantly lower in the insulinoma group at 4.7 ± 0.4% compared to the healthy control group at 5.7 ± 0.3% (p < 0.001), and GA was significantly lower in the insulinoma group at 11.6 ± 1.8% compared to the healthy control group at 14.5 ± 1.0% (p < 0.001). According to a receiver operating characteristic (ROC) analysis, optimal cutoff values of HbA1c and GA for the diagnosis of insulinoma were 5.0 and 12.4%, respectively. Area under the curve values of HbA1c and GA were 0.970 and 0.929, respectively, showing no significant difference (p = 0.399).
CONCLUSIONS: In the present study, HbA1c and GA values in patients with insulinoma were significantly lower compared to the healthy controls, and effective cutoff values for screening were shown in the diagnosis of insulinoma for the first time. HbA1c and GA can be useful indices for insulinoma screening. Because malignant insulinoma have a similar diagnostic process to that of benign insulinoma, these could be useful for malignant insulinoma.

BACKGROUND: It is known that an immunoglobulin abnormality affects various clinical laboratory measurements and leads to abnormal values. We experienced a case of monoclonal gammopathy of undetermined significance (MGUS) showing a falsely low plasma glycated albumin (GA) level.
METHODS: The patient was a 75-y-old male who visited our hospital for thrombocytosis identified during a medical checkup. Based on further examinations, he was diagnosed with MGUS (IgM-κ type). Laboratory examinations revealed that the plasma GA level was significantly low at -1.3% but the serum GA level was reasonable at 15.5%. We investigated the cause of the falsely low plasma GA level.
RESULTS: The patient\'s plasma became turbid after mixing with the first reagent for GA measurement. The plasma GA level was increased by dilution of the plasma. The plasma GA level was falsely decreased only at the time of measurement on a sample collected using a blood-collecting tube with heparin sodium. The GA level was decreased by adding heparin sodium to the patient\'s serum, whereas the GA level was increased by neutralization of the patient\'s plasma with protamine sulfate. The GA level was increased after adding polyethylene glycol to the patient\'s plasma. Serum GA levels in healthy controls were decreased by adding purified M protein from the patient\'s serum.
CONCLUSIONS: We report a patient with MGUS whose plasma GA concentration was falsely decreased by M protein when blood was drawn in a heparin sodium-containing tube.

To elucidate the individual impacts of insulin and blood glucose on cancer risk, we investigated the association of plasma C-peptide, a surrogated marker of insulin and glycated albumin (GA), a more stable marker of blood glucose, with all-site and site-specific cancer risk by mutually accounting for their confounding effects. The study was prospectively conducted with nearly 4,000 cancer cases arising in our population-based cohort of 33,736 subjects who answered the baseline questionnaire and supplied blood samples. After exclusion of subjects with apparent DM, analysis was done in 3,036 cancer cases and 3,667 subcohort subjects. Among men and women combined, highest levels of C-peptide were statistically significantly associated with an increased risk of all-site [Hazard ratio (HR): 1.21; 95% confidence interval: 1.02-1.42], colon [1.73; 1.20-2.47], liver [3.23; 1.76-5.91], kidney, renal pelvis and ureter cancers [2.47; 1.07-5.69], compared to the respective lowest levels, after adjustment for GA levels. Among these C-peptide-related cancers, colon and liver cancers also showed an increased risk associated with elevated GA levels independently of C-peptide levels. The corresponding HRs for colon and liver cancers compared to the highest and lowest GA levels were 1.43 [1.02-2.00] and 2.02 [1.15-3.55], respectively. Effect modification by gender was only evident for the association between C-peptide and colon cancer (p for interaction = 0.04). Higher insulin levels, independently of higher blood glucose levels, may be relevant to DM-related carcinogenesis for several cancer sites. Examination of circulating insulin levels is a plausible option in evaluating cancer risk even in individuals who have not developed DM.