scholarly journals Endothelial Dysfunction and Advanced Glycation End Products in Patients with Newly Diagnosed Versus Established Diabetes: From the CORDIOPREV Study

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 238
Author(s):  
Silvia de la Cruz-Ares ◽  
Magdalena P. Cardelo ◽  
Francisco M. Gutiérrez-Mariscal ◽  
José D. Torres-Peña ◽  
Antonio García-Rios ◽  
...  

Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ≥ 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.

2021 ◽  
pp. 1-7
Author(s):  
Tommaso Aversa ◽  
Rosaria Maddalena Ruggeri ◽  
Domenico Corica ◽  
Maria Teresa Cristani ◽  
Giorgia Pepe ◽  
...  

<b><i>Objective:</i></b> No data are available on advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in pediatric patients with Hashimoto’s thyroiditis (HT). The present study was aimed to simultaneously evaluate serum levels of sRAGE, AGEs, and advanced oxidation protein products (AOPPs) and investigate the relationships between these oxidative stress markers and clinical and biochemical parameters of thyroid function in euthyroid children with HT. <b><i>Design:</i></b> This is a case-control study carried out in a single university hospital center. <b><i>Methods:</i></b> We enrolled 19 newly diagnosed euthyroid HT pediatric patients (3 M, 16 F; median age 12.44 years, range 6.54–15.81 years) and 16 age-, sex-, and BMI-matched healthy controls (5 M, 11 F; median age 12.83 years, range 5.68–15.07 years). None was on levothyroxine treatment. The exclusion criteria were autoimmune, inflammatory, and infection comorbidities. Patients did not differ significantly from controls with regard to lipid or for anthropometric parameters. <b><i>Results:</i></b> sRAGE levels were significantly lower in HT patients (median 414.30 pg/mL, range 307.30–850.30 pg/mL) than in controls (561.30, 273.20–1121.60 pg/mL; <i>p</i> = 0.034). No differences emerged between patients and controls with regard to serum AGEs (124.25 AU/g prot, 71.98–186.72 vs. 133.90, 94.06–200.78 AU/g prot, <i>p</i> = 0.707) and AOPPs (1.13 nmol/mL, 0.62–1.83 vs. 1.17, 0.76–1.42 nmol/mL, <i>p</i> = 0.545). <b><i>Conclusions:</i></b> sRAGE levels were decreased in euthyroid children/adolescents at the onset of HT, suggesting that autoimmunity per se seems to play an important role in such a reduction of sRAGE, irrespective of any functional alteration. Children and adolescents suffering from HT may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.


2019 ◽  
Vol 10 (2) ◽  
pp. 58
Author(s):  
Ines KNANI ◽  
Hassan BOUZIDI ◽  
Albert LECUBE ◽  
Jawhar GHARBI ◽  
Mohsen KERKENI

Introduction: No data regarding the relationship of carotid intima media thickness (IMT) and serum advanced glycation end products (AGEs) levels in patients with rheumatoid arthritis (RA). The aim of this study is to evaluate the association between IMT and serum pentosidine, CML and MGO levels in patients with longstanding RA.Methods: In a cross-sectional study, 80 consecutive RA patients with longstanding disease were included and compared with 30 age and sex-matched healthy controls. IMT was measured using ultrasonography. AGEs such as pentosidine, Ne-carboxymethyllysine (CML) and methylglyoxal (MGO) as an intermediate of glycation, were determined by ELISA.Results: Serum pentosidine, CML and MGO levels were increased in RA patients vs control subjects (P = 0.001; P < 0.001; P < 0.001 respectively). IMT was increased with disease activity of RA (P = 0.004) and was associated with serum pentosidine (r = 0.460, P < 0.001), serum CML (r = 0.549, P < 0.001) and serum MGO (r = 0.658, P < 0.001). Furthermore, in a multiple stepwise regression analysis CML and MGO were independently associated with IMT (b= 0.333, P = 0.007; b = 0.690, P < 0.001, respectively).Conclusion: serum pentosidine, CML and MGO were increased in RA patients and were significantly related to IMT. Serum CML and MGO were independently associated with IMT.


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.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2958
Author(s):  
Ryuto Nasu ◽  
Ayako Furukawa ◽  
Keita Suzuki ◽  
Masayoshi Takeuchi ◽  
Yoshiki Koriyama

Nutritional factors can affect the risk of developing neurological disorders and their rate of progression. In particular, abnormalities of carbohydrate metabolism in diabetes mellitus patients lead to an increased risk of neurological disorders such as Alzheimer’s disease (AD). In this study, we investigated the relationship between nervous system disorder and the pathogenesis of AD by exposing SH-SY5Y neuroblastoma cells to glyceraldehyde (GA). We previously reported that GA-derived toxic advanced glycation end products (toxic AGEs, TAGE) induce AD-like alterations including intracellular tau phosphorylation. However, the role of TAGE and their target molecules in the pathogenesis of AD remains unclear. In this study, we investigated the target protein for TAGE by performing two-dimensional immunoblot analysis with anti-TAGE antibody and mass spectrometry and identified β-tubulin as one of the targets. GA treatment induced TAGE-β-tubulin formation and abnormal aggregation of β-tubulin, and inhibited neurite outgrowth in SH-SY5Y cells. On the other hand, glucose-derived AGEs were also involved in developing AD. However, glucose did not make abnormal aggregation of β-tubulin and did not inhibit neurite outgrowth. Understanding the underlying mechanism of TAGE-β-tubulin formation by GA and its role in neurodegeneration may aid in the development of novel therapeutics and neuroprotection strategies.


2019 ◽  
Vol 75 (10) ◽  
pp. 1894-1898 ◽  
Author(s):  
Varinderpal S Dhillon ◽  
Permal Deo ◽  
Ann Chua ◽  
Phil Thomas ◽  
Michael Fenech

Abstract Apolipoprotein-ε4 (APOE-ε4)—common variant is a major genetic risk factor for cognitive decline and Alzheimer's disease (AD). An accelerated rate of biological aging could contribute to this increased risk. Glycation of serum proteins due to excessive glucose and reactive oxygen species leads to the formation of advanced glycation end products (AGEs)—a risk factor for diabetes and AD, and decline in motor functioning in elderly adults. Aim of present study was to investigate impact of APOE-ε4 allele containing genotype and accumulation of AGEs in plasma on telomere length (TL). Results showed that TL is significantly shorter in APOE-ε4 carriers compared with non-APOE-ε4 carriers (p = .0003). Higher plasma glucose level was associated with shorter TL irrespective of APOE-ε4 allele containing genotype (r = −.26; p = .0004). With regard to AGEs, higher plasma glyoxal and fluorescent AGEs concentrations were inversely related to TL (r = −.16; p = .03; r = −.28; p = .0001), however, plasma Nε-(carboxymethyl)lysine levels didn't correlate with TL (r = −.04; p = .57). Results support the hypotheses that APOE-ε4 carriers have shorter telomeres than noncarriers and telomere erosion is increased with higher concentration of glucose, fluorescent AGEs, and glyoxal.


2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii596-iii596
Author(s):  
Paulo Gregório ◽  
Giane Favretto ◽  
Regiane da Cunha ◽  
Alessandra Becker-Finco ◽  
Guilherme Sassaki ◽  
...  

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