scholarly journals Receptor of advanced glycation end products and cardiovascular risk in elderly with type 2 diabetes mellitus

Author(s):  
Claudia Borsa ◽  
Daniela Gradinaru ◽  
Denisa Margina ◽  
Gabriel Ioan Prada ◽  
Catalina Pena

The interaction of Advanced Glycation End products (AGEs) and their specific receptor, Receptor for Advanced Glycation End products (RAGE) play an important role in diabetes and vascular complications. Engagement of RAGE by AGEs leads to activation of cellular signaling pathways and vascular dysfunction. The soluble RAGE (sRAGE) acts as a decoy receptor for AGEs. The aim of this study was to evaluate the soluble RAGE in elderly subjects with T2DM and its relationships with glycoxidative, inflammatory and cardiovascular risk markers. The serum AGEs, sRAGE, interleukine- 6 (IL-6), lipid profile, glycemic status, uric acid, creatinine and cardiovascular risk markers were determined in elderly subjects with type 2 diabetes mellitus (T2DM, N=72, 75±4 years old) and aged-match healthy subjects (N=15, 76±3 years old). Significant higher levels of AGEs and AGEs/sRAGE ratio concomitantly with significant lower levels of sRAGE were pointed out in elderly subjects with T2DM as compared to control. The values of AGEs/sRAGE ratio were significantly positively associated (P<0.05) with atherogenic, inflammatory and cardiovascular risk markers and significantly negatively with anti-atherogenic lipoproteins (P<0.05). The multivariate regression analyses showed that atherogenic index was an independent predictor of sRAGE levels and AGEs/sRAGE ratio values. The associations of soluble RAGE and the AGEs/sRAGE ratio with atherogenic and inflammatory markers could reflect the protective role of soluble variants of RAGE in atherosclerosis and diabetes vascular complications.

2004 ◽  
Vol 5 (2) ◽  
pp. 163-169 ◽  
Author(s):  
A. E. Buchs ◽  
A. Kornberg ◽  
M. Zahavi ◽  
D. Aharoni ◽  
C. Zarfati ◽  
...  

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin–stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 ± 0.06 in patients with complications and 0.05 ± 0.06 patients without complications (P= .004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 ± 0.29 in patients with complications and 0.21 ± 0.18 in patients without complications (P= .003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/106PBMCs) was 18.4 ± 13.2 in patients with complications and 6.96 ± 5.2 in patients without complications (P= .003). It increased 3-fold in both groups after stimulation (P= .001). TF antigen (pg/106PBMCs) was 33.7 ± 28.6 in patients with complications, 10.4 ± 7.8 in patients without complications (P= .02). Stimulation tripled TF antigen in both groups of patients (P= .001). The RAGE/TF axis is up-regulated inT2Dpatients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D.


Author(s):  
Reiko Saito ◽  
Shunsuke Araki ◽  
Yukiyo Yamamoto ◽  
Koichi Kusuhara

AbstractBackground:Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) play an important role in the development of diabetic vascular complications. This study aimed at investigating the relationship between the soluble form of RAGE (sRAGE), endogenous secretory RAGE (esRAGE), and pentosidine in childhood diabetes.Methods:The study included 18 children with type 1 diabetes mellitus (T1DM), 10 with type 2 DM (T2DM), and 22 age-matched, non-diabetic children (control).Results:Serum sRAGE levels in the T1DM (2557.7 pg/mL) were significantly higher than both T2DM (1956.4 pg/mL) and control (1658.5 pg/mL). The circulating levels of esRAGE in T1DM and T2DM children were similar, but significantly higher than those of control. Serum pentosidine levels in the T1DM group were positively correlated with serum sRAGE and esRAGE levels, but not with anthropometric or biochemical measurements. The duration of diabetes and esRAGE levels were independent predictors of the circulating sRAGE levels.Conclusions:Unlike adults, children with diabetes exhibit high circulating esRAGE levels, and both sRAGE and esRAGE levels are correlated with pentosidine levels. These results suggest that circulating sRAGE and esRAGE in children may be surrogate markers for progressive glucose toxicity in pediatric patients with childhood-onset diabetes.


Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed ◽  
Admin

Abstract Objective: To investigate the association of receptor for advanced glycation end products (RAGE) gene polymorphism 429T/C (rs1800625) with diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) levels in Pakistani patients with Type 2 diabetes. Methods: A case-control study, conducted from January 2017 to December 2018, including 150 healthy controls (HC), 150 diabetics without retinopathy (DWR) and 150 DR patients. Ethical approval was taken from Ethics Review Committee of Islamic International Medical College - Riphah International University (RIU). Genotyping for 429T/C was done by Tetra-primer amplification refractory mutation system – polymerase chain reaction (T-ARMS-PCR). Serum sRAGE levels were measured by enzyme-linked immunosorbent assay (ELISA). Data was analysed to calculate descriptive and inferential statistics to compare genotype/allelic frequencies, biochemical markers and serum sRAGE among three study groups. Results: The frequency of TT, TC and CC genotypes of 429T/C polymorphism were: 91.3%, 6.7%, 2% in HC, 88.6%, 8.7%, 2.7% in DWR and 84.7%, 12.0%, 3.3 % in DR groups. No significant association of 429T/C genotypic and allelic frequencies with DWR and DR along with its subtypes, non- proliferative (NPDR) and proliferative (PDR) was observed. Upon further stratifying NPDR into mild, moderate and severe, an association of heterozygous TC with severe NPDR was observed compared to DWR in univariate and multinomial regression analysis. Serum sRAGE levels were significantly high in PDR patients compared to DWR and were positively correlated with fasting plasma glucose (FPG) in DR group.  


2021 ◽  
Vol 8 ◽  
Author(s):  
Lingwen Ying ◽  
Yun Shen ◽  
Yang Zhang ◽  
Yikun Wang ◽  
Yong Liu ◽  
...  

Aims: Advanced glycation end products (AGEs) were reported to be correlated with the development of diabetes, as well as diabetic vascular complications. Therefore, this study aimed at investigating the association between AGEs and lower-extremity atherosclerotic disease (LEAD).Methods: A total of 1,013 type 2 diabetes patients were enrolled. LEAD was measured through color Doppler ultrasonography. The non-invasive skin autofluorescence method was performed for AGEs measurement. Considering that age plays an important role in both AGEs and LEAD, age-combined AGEs, i.e., AGEage index (define as AGEs × age/100) was used for related analysis.Results: The overall prevalence of LEAD was 48.9% (495/1,013). Patients with LEAD showed a significantly higher AGEage (p &lt; 0.001), and the prevalence of LEAD increased with ascending AGEage levels (p for trend &lt; 0.001). Logistic regression analysis revealed that AGEage was significantly positively associated with risk of LEAD, and the odds ratios of presence of LEAD across quartiles of AGEage were 1.00, 1.72 [95% confidence interval (CI) = 1.14–2.61], 2.72 (95% CI = 1.76–4.22), 4.29 (95% CI = 2.69–6.85) for multivariable-adjusted model (both p for trend &lt; 0.001), respectively. The results were similar among patients of different sexes, body mass index, and with or without diabetes family history. Further, AGEage presented a better predictive value for LEAD than glycated hemoglobin A1c (HbA1c), with its sensitivity, specificity, and area under the curve of 75.5% (95% CI = 71.6–79.2%), 59.3% (95% CI = 54.9–63.6%), and 0.731 (0.703–0.758), respectively.Conclusion: AGEage, the non-invasive measured skin AGEs combined with age, seems to be a more promising approach than HbA1c in identifying patient at high risk of LEAD.


2012 ◽  
Vol 17 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Tommaso de Giorgis ◽  
Ebe D'Adamo ◽  
Cosimo Giannini ◽  
Valentina Chiavaroli ◽  
Antonino Scarinci ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 275-LB
Author(s):  
EDWIN R. MIRANDA ◽  
JR. KELLY N. FULLER ◽  
RYAN PERKINS ◽  
PAUL J. BEISSWENGER ◽  
SARAH S. FARABI ◽  
...  

Blood ◽  
2012 ◽  
Vol 119 (25) ◽  
pp. 6136-6144 ◽  
Author(s):  
Weifei Zhu ◽  
Wei Li ◽  
Roy L. Silverstein

Abstract Diabetes mellitus has been associated with platelet hyperreactivity, which plays a central role in the hyperglycemia-related prothrombotic phenotype. The mechanisms responsible for this phenomenon are not established. In the present study, we investigated the role of CD36, a class-B scavenger receptor, in this process. Using both in vitro and in vivo mouse models, we demonstrated direct and specific interactions of platelet CD36 with advanced glycation end products (AGEs) generated under hyperglycemic conditions. AGEs bound to platelet CD36 in a specific and dose-dependent manner, and binding was inhibited by the high-affinity CD36 ligand NO2LDL. Cd36-null platelets did not bind AGE. Using diet- and drug-induced mouse models of diabetes, we have shown that cd36-null mice had a delayed time to the formation of occlusive thrombi compared with wild-type (WT) in a FeCl3-induced carotid artery injury model. Cd36-null mice had a similar level of hyperglycemia and a similar level of plasma AGEs compared with WT mice under this condition, but WT mice had more AGEs incorporated into thrombi. Mechanistic studies revealed that CD36-dependent JNK2 activation is involved in this prothrombotic pathway. Therefore, the results of the present study couple vascular complications in diabetes mellitus with AGE-CD36–mediated platelet signaling and hyperreactivity.


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