Plasma Levels of Pentosidine, Carboxymethyl-Lysine, Soluble Receptor for Advanced Glycation End Products, and Metabolic Syndrome: The Metformin Effect

Metabolic syndrome (MetS) is considered one of the most important public health problems. Several and controversial studies showed that the role of advanced glycation end products (AGEs) and their receptor in the development of metabolic syndrome and therapeutic pathways is still unsolved. We have investigated whether plasma pentosidine, carboxymethyl-lysine (CML), and soluble receptor for advanced glycation end products (sRAGE) levels were increased in patients with MetS and the effect of metformin in plasma levels of pentosidine, CML, and sRAGE. 80 control subjects and 86 patients were included in this study. Pentosidine, CML, and sRAGE were measured in plasma by enzyme-linked immunosorbent assay (ELISA). Plasma pentosidine, CML, and sRAGE levels were significantly increased in patients compared to control subjects ( < 0.001, < 0.001, and = 0.014, resp.). Plasma levels of pentosidine were significantly decreased in patients who received metformin compared to untreated patients ( = 0.01). However, there was no significant difference between patients treated with metformin and untreated patients in plasma CML levels. Plasma levels of sRAGE were significantly increased in patients who received metformin and ACE inhibitors ( < 0.001 and = 0.002, resp.). However, in a multiple stepwise regression analysis, pentosidine, sRAGE, and drugs treatments were not independently associated. Patients with metabolic syndrome showed increased levels of AGEs such as pentosidine and CML. Metformin treatment showed a decreased level of pentosidine but not of CML. Therapeutic pathways of AGEs development should be taken into account and further experimental and in vitro studies merit for advanced research

Methylglyoxal: A Relevant Marker of Disease Activity in Patients with Rheumatoid Arthritis

Background. The contribution of methylglyoxal (MGO) and soluble receptor for advanced glycation end products (sRAGE) in the presence of rheumatoid arthritis (RA) is still unknown. We investigated whether serum MGO and sRAGE were related to the presence of disease activity in RA. Methods. 80 patients with RA and 30 control subjects were included in a cross-sectional study. The severity of RA was assessed using the disease activity score for 28 joints (DAS28). Serum MGO and sRAGE were measured by ELISA. Results. Serum MGO levels were significantly higher in patients with RA versus control subjects (P<0.001) and were increased in RA patients with higher disease activity versus RA patients with moderate disease activity (P=0.019). Serum sRAGE concentrations were significantly decreased in RA patients with higher disease activity versus RA patients with moderate disease activity and versus control subjects (P=0.004; P=0.002, resp.). A multiple logistic regression analysis demonstrated that MGO was independently associated with the presence of activity disease in RA (OR = 1.17, 95% CI: 1.02–1.31, P=0.01). Conclusion. Serum MGO and sRAGE levels are inversely related to the activity of RA, and MGO is independently associated with a higher disease activity of RA

Increased skin autofluorescence of advanced glycation end products (AGEs) in subjects with cardiovascular risk factors

Background As a clinical and non-invasive tool, the AGE Reader measures skin autofluorescence (SAF) to estimate the accumulation of advanced glycation end products (AGEs) in the skin. Accumulation of AGEs has been implicated in several inflammation-associated diseases, including diabetes and cardio-metabolic diseases. This study aimed to assess SAF in subjects with and without cardiovascular risk (CVR) factors and examine the association between SAF and various bio-clinical parameters. Methods In a cross-sectional study, we included 250 participants between 19 and 86 years of age divided into two groups: a healthy group (n = 88) and subjects with CVR factors (n = 162 in total, diabetes n = 48, hypertension n = 62, and both n = 52). We assessed skin AGE measures and biological and clinical data. Results SAF was significantly higher in subjects with CVR factors than in healthy participants (2.42 +/- 0.38 vs 1.90 +/- 0.29 respectively; p &lt; 0.001). SAF was associated with age, gender, BMI, duration of diabetes, HbA1c, triglyceride, and obesity. Multivariate analysis showed that age and duration of diabetes were the independent determinants of SAF. The ROC analysis indicated that a SAF &gt; 2.25 AU was the optimal cut-off point to predict the presence of diabetes and/or hypertension and dyslipidemia (p &lt; 0.001). Conclusion This Tunisian population-based study shows an increased SAF level in subjects with diabetes and/or hypertension and dyslipidemia compared to healthy subjects. The AGE Reader device is a rapid and non-invasive tool in clinical practice to evaluate and screen CVR factors in Tunisia with a North African phototype.</p

Lipoblastoma in childhood: About 10 cases

Background: Lipoblastoma is a rare benign mesenchymal tumour of embryonal fat that occurs almost exclusively in infants and children. This determined the epidemiological, clinical and therapeutic aspect of this disease. Materials and Methods: A total of 10 cases of pathologically proven lipoblastoma from 2003 to 2012 were reviewed. Results: There were six boys and four girls ranging in age from 7 months to 9 years. A soft-tissue mass was the main complain in nine patients. The various locations of the mass were mediastinal, thigh, buttock, inguino-scrotal, the greater omentum and the Latissimus dorsi. Lesions measured 5-15 cm. complete excision was done. The median time of follow-up was 42 months (ranges between 18 and 84 months). There were no recurrences. Conclusion: It is important to consider lipoblastoma in the diagnosis of a rapidly enlarging fatty mass in children. Complete resection is the only definitive treatment and should not be delayed when impingement on surrounding structures is imminent. There is a tendency for these lesions to recur despite presumed complete excision. Therefore, follow-up for a minimum of 5 years is recommended

Weak Association between Skin Autofluorescence Levels and Prediabetes with an ILERVAS Cross-Sectional Study

A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of prediabetes is unclear. A cross-sectional study was conducted in 4181 middle-aged subjects without diabetes. Prediabetes (n = 1444) was defined as a glycosylated hemoglobin (HbA1c) level between 39 and 47 mmol/mol (5.7 to 6.4%), and skin autofluorescence (SAF) measurement was performed to assess AGEs. A multivariable logistic regression model and receiver operating characteristic curve were used. The cohort consisted of 50.1% women with an age of 57 [52;62] years, a BMI of 28.3 [25.4;31.6] kg/m, and a prevalence of prediabetes of 34.5%. Participants with prediabetes showed higher SAF than control participants (2.0 [1.7;2.2] vs. 1.9 [1.7;2.2], p < 0.001). However, HbA1c was not significantly correlated with SAF levels (r = 0.026, p = 0.090). In addition, the SAF level was not independently associated with prediabetes (OR = 1.12 (0.96 to 1.30)). Finally, there was no good cutoff point for SAF to identify patients with prediabetes (AUC = 0.52 (0.50 to 0.54), sensitivity = 0.61, and 1-specificity = 0.56). Given all of this evidence, we can conclude that although there is an increase in SAF levels in participants with prediabetes, the applicability and clinical relevance of the results is low in this population

Skin Autofluorescence Measurement in Subclinical Atheromatous Disease : Results from the ILERVAS Project

Aim: Advanced glycation end-products (AGEs) have been involved in the atherogenic process in the high-risk population. The goal of this study was to demonstrate that AGEs are related to subclinical atheromatous disease in subjects with low to moderate vascular risk. Methods: A cross-sectional study in which 2,568 non-diabetic subjects of both sexes without cardiovascular disease were included. Subcutaneous content of AGEs was assessed by skin autofluorescence (SAF) and subclinical atheromatous disease was measured by assessing the atheromatous plaque burden in carotid and femoral regions using ultrasonography. In addition, serum pentosidine, carboxymethyl-lysine (CML) and AGE receptors (RAGE) were assessed in a nested case-control study with 41 subjects without plaque and 41 individuals subjects with generalized disease. Results: Patients with atheromatous plaque had a higher SAF than those with no plaque (1.9 [1.7 to 2.3] vs. 1.8 [1.6 to 2.1] arbitrary units (AU), p % 0.001). The SAF correlated with the total number of affected regions (r = 0.171, p < 0.001), increasing progressively from 1.8 [1.6 to 2.1] AU in those without atheromatous disease to 2.3 [1.9 to 2.7] AU in patients with ≥ 8 plaques (p < 0.001). A correlation was also observed between SAF and the total plaque area (r = 0.113, p < 0.001). The area under the Receiver Operating Characteristic curve was 0.65 (0.61 to 0.68) for identifying male subjects with atheromatous disease. The multivariable logistic regression model showed a significant and independent association between SAF and the presence of atheromatous disease. However, no significant differences in serum pentosidine, CML, and RAGE were observed. Conclusions: Increased subcutaneous content of AGEs is associated with augmented atheromatous plaque burden. Our results suggest that SAF may provide clinically relevant information to the current strategies for the evaluation of cardiovascular risk, especially among the male population