scholarly journals Relationship Between Advanced Glycation End Products and Their Receptor, sRAGE and Cardiovascular Diseases Risk in Adults with T2D and Vitamin D Insufficiency/deficiency (FS12-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Justina Owusu ◽  
Fatma Huffman ◽  
Juan Liuzzi ◽  
Tan Li ◽  
Vijaya Narayanan

Abstract Objectives Advanced Glycation End Products, (AGEs) and their soluble receptor (sRAGE) have been implicated in the development of complications and mortality among individuals with type 2 diabetes (T2D). There is limited information on the relationship between AGEs and sRAGE and risk of cardiovascular diseases (CVD) in minority groups, who have a higher burden of T2D. The relationship between AGEs and sRAGE and CVD risks in adults with T2D and vitamin D insufficiency/deficiency was assessed in a minority population. Methods A cross sectional study of Hispanics and African Americans with T2D (n = 64, 41 women and 23 men, mean age = 54 ± 9) recruited from two clinics in Miami Dade. Systolic (SBP) and diastolic blood pressure (DBP), weight and height measurement and serum lipid profile were completed. ELISA kits were used to assess serum levels of AGEs (Biotang Inc/TSZ Elisa, Waltham, MA, USA) and sRAGE (Biotang Inc/TSZ Elisa, Waltham, MA, USA). Multiple linear regression was used to assess association between AGEs, sRAGE and CVD risks. Results A negative and significant association between AGEs and high-density lipoprotein cholesterol (HDL-C)(B = −0.551, P = 0.029) was found. The relationship between AGEs and HDL-C persisted after adjusting for covariates (P < 0.05). sRAGE was significantly associated with SBP (B = 0.015, P = 0.025) and diastolic blood pressure DBP (B = 0.0271, P = 0.037). Results loss significance when association between sRAGE and DBP and SBP were adjusted for covariates such as age, body mass index (BMI), smoking and alcohol intake. Conclusions Our results suggest that AGEs and sRAGE are related to markers of cardiovascular risk such as HDL-C, SBP and DBP in the study population of African Americans and Hispanics with T2D and vitamin D insufficiency/deficiency. Measures on reducing serum levels of AGEs and improving sRAGE and vitamin D are warranted in these populations for risk reduction of CVD. Funding Sources Partial funding for this research was provided through an NIH/NIDDK sponsored grant.

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahsa Omidian ◽  
Mahmoud Djalali ◽  
Mohammad Hassan Javanbakht ◽  
Mohammad Reza Eshraghian ◽  
Maryam Abshirini ◽  
...  

Abstract Background Several researches have recommended vitamin D possible health benefits on diabetic complications development, but a few number of studies have been accomplished on the molecular and cellular mechanisms. Certain cellular pathways modification and also some transcription factors activation may protect cells from hyperglycemia condition induced damages. This study purpose was to determine the vitamin D supplementation effect on some key factors [advanced glycation end products (AGEs) signaling pathway] that were involved in the diabetic complications occurrence and progression for type-2 diabetes participants. Methodology 48 type-2 diabetic patients (T2DM) randomly divided into two groups (n = 24 per group), receiving: 100-µg vitamin D or placebo for 3 months. At this study beginning and the end, the receptor expression for advanced glycation end products (RAGE) and glyoxalase I (GLO1) enzyme from peripheral blood mononuclear cells (PBMCs) and AGEs and tumor necrosis factor-α (TNF-α) serum levels were measured by the use of real-time PCR and ELISA methods, respectively. Results This study results demonstrated that vitamin D supplementation could down-regulate RAGE mRNA [fold change = 0.72 in vitamin D vs. 0.95 in placebo) P = 0.001)]. In addition, no significant changes were observed for GLO1 enzyme expression (P = 0.06). This study results also indicated that vitamin D serum level significantly increased in vitamin D group (P < 0.001). Moreover, AGES and TNF-α serum levels significantly reduced in vitamin D group, but they were remained unchanged in the placebo group. Conclusion In conclusion, vascular complications are more frequent in diabetic patients, and vitamin D treatment may prevent or delay the complications onset in these patients by AGEs serum level and RAGE gene expression reducing. Trial registration NCT03008057. Registered December 2016


Author(s):  
Vienna E. Brunt ◽  
Abigail G. Casso ◽  
Rachel A. Gioscia-Ryan ◽  
Zachary J. Sapinsley ◽  
Brian P. Ziemba ◽  
...  

Aging is associated with stiffening of the large elastic arteries and consequent increases in systolic blood pressure (SBP), which together increase cardiovascular disease risk; however, the upstream mechanisms are incompletely understood. Using complementary translational approaches in mice and humans, we investigated the role of the gut microbiome-derived metabolite trimethylamine N-oxide (TMAO) in age-related aortic stiffening and increased SBP. Aortic stiffness was measured using carotid-femoral or aortic pulse wave velocity (PWV) in humans and mice, respectively. Study 1: Plasma TMAO concentrations were elevated ( P <0.001) in healthy middle-aged to older (6.3±5.8 µmol/L) versus young (1.8±1.4 µmol/L) humans and positively related to carotid-femoral PWV ( r 2 =0.15, P <0.0001) and SBP ( r 2 =0.09, P <0.001), independent of traditional cardiovascular risk factors. Study 2: Dietary supplementation with TMAO increased aPWV in young mice and exacerbated the already elevated aPWV of old mice, accompanied by increases in SBP of ≈10 mm Hg in both groups. TMAO-supplemented versus control-fed mice also had higher intrinsic mechanical stiffness of the aorta (stress-strain testing) associated with higher aortic abundance of advanced glycation end-products, which form crosslinks between structural proteins to promote aortic stiffening. Study 3: Ex vivo incubation of aortic rings with TMAO increased intrinsic stiffness, which was attenuated by the advanced glycation end-products crosslink breaker alagebrium and prevented by inhibition of superoxide signaling. TMAO induces aortic stiffening and increases SBP via formation of advanced glycation end-products and superoxide-stimulated oxidative stress, which together increase intrinsic wall stiffness. Increases in circulating TMAO with aging represent a novel therapeutic target for reducing risk of aortic stiffening-related clinical disorders.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1829-1829
Author(s):  
Justina Owusu ◽  
Fatma Huffman ◽  
Juan Liuzzi ◽  
Sahar Ajabshir ◽  
Tan Li ◽  
...  

Abstract Objectives Diabetes related complications include kidney, eye, heart diseases and amputations. Advanced Glycation End Products, (AGEs) are biomarkers of T2D. AGEs are covalent adducts formed from reactions between sugars and proteins or lipids. Vitamin D deficiency, prevalent with T2D, increases oxidative stress and inflammation that promotes the formation of AGEs. This study assessed the effect of 4000 IU vitamin D supplements on AGEs in adults with T2D and vitamin D deficiency/insufficiency. Methods We assessed changes in serum AGEs of 41 African Americans and Hispanics with T2D and hypovitaminosis D who were supplemented with 4000 IU of vitamin D3 for 6 months. Total AGEs were assessed using commercially available kits (Biotang Inc/TSZ Elisa, Waltham, MA, USA). Results The mean age of study participants was 54 ± 8 years. AGEs significantly increased at 3 months compared to baseline (Mean Difference = −13.70 ng/ml, P = 0.007). The mean level of AGEs decreased significantly at 6 months of supplementation (Mean Difference = 9.79 ng/ml, P = 0.020). Additionally, the mean serum levels of AGEs were significantly higher at 3 months compared to 6 months among study participants (Mean Difference = 24.52 ng/ml, P &lt; 0.0001). Conclusions Daily supplementation of 4000 IU vitamin D3 reduced AGEs at 6 months but not at 3 months. Supplementation of this minority population with vitamin D may delay the accumulation of AGEs and complications related to T2D. Funding Sources Funding for this research was provided through an NIH/NIDDK sponsored grant.


2010 ◽  
Vol 30 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Nobuhiro Tahara ◽  
Sho-ichi Yamagishi ◽  
Takanori Matsui ◽  
Masayoshi Takeuchi ◽  
Yoshikazu Nitta ◽  
...  

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