scholarly journals The Ratio of Oxidized Lipoprotein(a) to Native Lipoprotein(a) and the Endothelial Function in Patients with Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (19) ◽  
pp. 4909 ◽  
Author(s):  
Kazuhiko Kotani ◽  
Shingo Yamada ◽  
Hirokazu Takahashi ◽  
Yoshitaka Iwazu ◽  
Toshiyuki Yamada

The ratio of oxidized lipoprotein(a) to native lipoprotein(a) (oxLp(a)/Lp(a)) may be a reasonable index for assessing endothelial dysfunction in type 2 diabetes mellitus (T2DM). The present study investigated whether the oxLp(a)/Lp(a) level is correlated with the endothelial function using the Endo-PATTM, a newly developed device, in patients with T2DM. A total of 63 patients with T2DM (mean age: 59 years old) were enrolled in the study. The patients’ serum Lp(a) and oxLp(a) levels were measured using an enzyme-linked immunosorbent assay. The reactive hyperemia index (RHI) level was measured using an Endo-PATTM 2000. A correlation analysis between the measured variables was conducted. Among the patients, the mean hemoglobin A1c was 7.8%. The median level of oxLp(a)/Lp(a) was 0.28 (interquartile range: 0.07–0.54), and the mean RHI was 1.8 (standard deviation: 0.4). In a multiple linear regression analysis, the oxLp(a)/Lp(a) level was an independent, significant, and inverse variable for the RHI level (β = −0.26, p < 0.05), along with male gender. A high oxLp(a)/Lp(a) level may reflect endothelial dysfunction, as assessed by the Endo-PATTM, in patients with T2DM. Further studies are warranted to confirm the observed findings.

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1712 ◽  
Author(s):  
Ali Mahdi ◽  
John Tengbom ◽  
Michael Alvarsson ◽  
Bernhard Wernly ◽  
Zhichao Zhou ◽  
...  

We recently showed that red blood cells (RBCs) from patients with type 2 diabetes mellitus (T2DM-RBCs) induce endothelial dysfunction through a mechanism involving arginase I and reactive oxygen species. Peroxynitrite is known to activate arginase in endothelial cells. Whether peroxynitrite regulates arginase activity in RBCs, and whether it is involved in the cross-talk between RBCs and the vasculature in T2DM, is unclear and elusive. The present study was designed to test the hypothesis that endothelial dysfunction induced by T2DM-RBCs is driven by peroxynitrite and upregulation of arginase. RBCs were isolated from patients with T2DM and healthy age matched controls. RBCs were co-incubated with aortae isolated from wild type rats for 18 h in the absence and presence of peroxynitrite scavenger FeTTPS. Evaluation of endothelial function in organ chambers by cumulative addition of acetylcholine as well as measurement of RBC and vessel arginase activity was performed. In another set of experiments, RBCs isolated from healthy subjects (Healthy RBCs) were incubated with the peroxynitrite donor SIN-1 with subsequent evaluation of endothelial function and arginase activity. T2DM-RBCs, but not Healthy RBCs, induced impairment in endothelial function, which was fully reversed by scavenging of RBC but not vascular peroxynitrite with FeTPPS. Arginase activity was up-regulated by the peroxynitrite donor SIN-1 in Healthy RBCs, an effect that was inhibited by FeTTPS. Healthy RBCs co-incubated with aortae in the presence of SIN-1 caused impairment of endothelial function, which was inhibited by FeTTPS or the arginase inhibitor ABH. T2DM-RBCs induced up-regulation of vascular arginase, an effect that was fully inhibited by FeTTPS. Collectively, our data indicate that RBCs impair endothelial function in T2DM via an effect that is driven by a peroxynitrite-mediated increase in arginase activity. This mechanism may be targeted in patients with T2DM for improvement in endothelial function.


2021 ◽  
Vol 16 (8) ◽  
pp. 616-621
Author(s):  
L.K. Sokolova ◽  
Yu.B. Belchina ◽  
V.V. Pushkarev ◽  
S.A. Cherviakova ◽  
T.S. Vatseba ◽  
...  

Background. Type 2 diabetes mellitus (T2DM) is closely associated with an increased risk of cardiovascular diseases. It was shown that endothelial dysfunction is one of the key pathological events in the development of chronic vascular diabetic complications. An important effect of endothelial dysfunction is that it increases the production and biological activity of the potent vasoconstrictor and the pro-inflammatory peptide — endothelin (ET). Metformin is used in the treatment of T2DM as a first-line medication. It has been shown that the mechanism of action of metformin may be associated with biochemical processes in the gastrointestinal tract. Brain natriuretic peptide (BNP) is used as a marker in the diagnosis of heart failure. The purpose of this work was to determine and compare ET-1, NT-proBNP and glucagon-like peptide-1 (GLP-1) blood levels in diabetic patients treated with metformin. Materials and methods. NT-proBNP, GLP-1, endothelin-1 and glycated hemoglobin were determined using enzyme-linked immunosorbent assay. To compare the data groups, Student’s t-test and one-way ANOVA were used. Results. The content of ET-1 in the blood of patients with T2DM significantly exceeds its concentration in the control samples. Monotherapy with metformin leads to a decrease in ET-1 levels by more than 65 %. The combination therapy of metformin with insulin causes even greater decrease in ET-1. The blood level of GLP-1 in patients with T2DM is significantly, more than 2 times, reduced compared to healthy people. After metformin treatment, the content of GLP-1 is increased to the control level. The concentration of NT-proBNP in the blood of diabetic patients more than 2 times exceeds the control values. Treatment with metformin leads to a decrease in the content of natriuretic peptide by more than 40 %. Conclusions. Thus, treatment with metformin causes a decrease in ET-1 and NT-proBNP concentrations, and an increase in blood GLP-1 of patients with type 2 diabetes. These events together may indicate a positive protective effect of metformin on the cardiovascular system.


2020 ◽  
Vol 2 (2) ◽  
pp. 46-55
Author(s):  
Li X ◽  
Wu W ◽  
Wang Y ◽  
Zhang X ◽  
Feng X ◽  
...  

Objective: Liraglutide (LIRA), a Glucagon-like peptide-1 (GLP-1) receptor agonist, showed potential vascular protective effects with the mechanism remained incompletely understood. Therefore, this study aimed to investigate whether LIRA exerts its effect on vascular endothelial function in rats with type 2 diabetes mellitus (T2DM) via caveolin-1/ endothelial oxide synthase (eNOS) expression. Methods: T2DM rats were used as study subjects and randomly divided into four groups: 1) Veh group, 2) Veh+LIRA group, 3) T2DM group, and 4) T2DM+LIRA group. All rats received either saline or LIRA 0.2 mg/kg (by i.p. injection) per day for 4 weeks. After the model was successfully established, vascular endothelial function was determined the effect of vasodilator to mesenteric artery rings. Immunofluorescence and western blot were performed to understand the molecular mechanism. Cultured HUVECs with small interfering RNA (siRNA) under high glucose (HG), NO concentration, and western blot were performed to understand the molecular mechanism between LIRA and vascular endothelial function. Results: Based on our results, the LIRA reduced hyperglycemia and ameliorated vascular endothelial dysfunction in type 2 diabetic mice. LIRA activated eNOS phosphorylation, suppressing oxidative stress and enhancing endothelium-dependent vasorelaxation of mesenteric arteries. Besides, from its anti-oxidative capacity, LIRA activated eNOS to dilate the mesenteric arteries via the downregulation of Cav-1. Conclusion: LIRA ameliorates vascular endothelial dysfunction in rats with type 2 diabetes mellitus via anti-oxidative and activated eNOS by downregulated Cav-1.


2016 ◽  
Vol 22 (2) ◽  
pp. 126-130 ◽  
Author(s):  
Carlos Alberto da Silva ◽  
Francisco Sérgio Lopes Vasconcelos-Filho ◽  
Marcus Serafim ◽  
Edson Botura ◽  
Roberta Cristina da Rocha-e-Silva ◽  
...  

Introduction: Diabetes mellitus is the most common metabolic disease worldwide. Endothelial dysfunction characteristic of these patients is one of the major risk factors for atherosclerosis. Early diagnosis of endothelial dysfunction is essential for the treatment especially of non-invasive manner, such as flow mediated dilation. Physical exercise is capable of generating beneficial adaptations may improve endothelial function. Objective: Identify the effect of physical exercise, using the clinical technique of ultrasound in the assessment of the endothelial function of patients with metabolic syndrome or type 2 diabetes mellitus. Methods: Thirty-one patients with type 2 diabetes mellitus or metabolic syndrome were studied, with a mean age (± SD) of 58±6 years, randomized into three groups. The training was performed for 50 minutes, four times a week. Before and after six weeks of training, subjects performed the endurance test and a study of the endothelial function of the brachial artery by high-resolution ultrasound. Results: After hyperemia, the percentage of arterial diameter was significantly higher for the high-intensity group (HI before = 2.52±2.85mm and after = 31.81±12.21mm; LI before = 3.23±3.52mm and after = 20.61±7.76mm; controls before = 3.56±2.33mm and after = 2.43±2.14mm; p<0.05). Conclusions: The high-intensity aerobic training improved the vasodilatation response-dependent endothelium, recorded by ultrasound, in patients with metabolic syndrome and type 2 diabetes.


2017 ◽  
Vol 89 (10) ◽  
pp. 87-94
Author(s):  
I T Murkamilov ◽  
I S Sabirov ◽  
V V Fomin ◽  
F A Yusupov

In recent years, one of the promising areas in clinical medicine is the study of impaired ments in endothelial function and arterial wall stiffness, which can be referred to as one of the important predictors of cardiovascular events in patients with chronic kidney disease, including that of diabetic etiology. There is strong evidence that endothelial function and great artery stiffness may be used as reliable clinical and instrumental indicators to evaluate the efficiency of therapeutic measures and the rate of progression of cardiovascular disorders in type 2 diabetes mellitus. The article presents data on the role of endothelial dysfunction and arterial wall stiffness in the progression of chronic kidney disease in type 2 diabetes mellitus and discusses the possibility of their correction with pharmacological agents.


Author(s):  
Nermien Abd El Rahman Ibraheim ◽  
Fatema El Zahraa Sayed Bukhary ◽  
Yehia Zakareia Mahmoud ◽  
Mahmoud Ragab Mohamed ◽  
Salama Rabei Abdel-Rahim

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
AA Garganeeva ◽  
EA Kuzheleva ◽  
VA Fedyunina ◽  
VA Aleksandrenko

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was funded by (subject of fundamental scientific research on a state assignment № АААА-А17-117052310073-6 от 23.05.2017 Introduction. Growth differentiation factor-15 (GDF-15) is a biomarker associated with inflammatory processes in the pathogenesis of chronic heart failure (CHF) which expresses in cardiomyocytes under pathological conditions. The relationship between the level of GDF-15 and type 2 diabetes mellitus (T2DM) has also been proven. It is necessary to study GDF-15 in patients with CHF and T2DM. Aim To investigate the association between serum GDF-15 levels in patients with CHF of ischemic etiology and the concentration of the main leukocyte fractions depending on presence or absence of T2DM. Material and methods. The study included 42 patients. The patients were divided into 2 groups. The first group consisted of patients with CHF and T2DM (n = 14). The second group  consisted of patients with CHF without T2DM (n = 28). Determination of GDF-15 concentration was carried out by enzyme-linked immunosorbent assay (BioVendor, Czech Republic). The absolute concentration of lymphocytes, neutrophils, as well as the ratio of neutrophils to lymphocytes in the blood were analyzed. Statistical analysis was performed using the Statistica software (v.10.0). The data were described as a median and interquartile range, the Mann-Whitney test was used to compare them. The correlation analysis was tested using the Spearman"s correlation coefficient. Results and discussion. The average level of the GDF-15 in the study groups was comparable: 2389 (2104; 3375) pg/ml and 2309 (2047; 3014) pg/ml in the first and second groups, respectively (p = 0.6). In the general cohort of CHF patients, the GDF-15 concentration was not correlate with the lymphocytes concentration (r = -0.001, p = 0.95), neutrophils (r = -0.14, p = 0.4) and the ratio of neutrophils to lymphocytes (r = -0.12, p = 0.25). At the same time, in the group of patients with T2DM, a significant negative correlation was revealed between the concentration of GDF-15 in the serum and the concentration of neutrophils (r = -0.6, p = 0.022). While both other analyzed parameters did not demonstrate significant correlations with GDF-15 (p &gt; 0.05). In the group of CHF patients without T2DM, no correlations were found between GDF-15 and the studied parameters, including neutrophils (r = 0.02, p = 0.3). Along with this the median of the neutrophils concentration did not vary among groups (3.5 (2.3; 5.3) vs 3.2 (2.7; 4.1) * 109 / l; p = 0.8). Conclusion The concentration of the inflammatory marker GDF-15 in the blood of patients with CHF in combination with T2DM correlates with the concentration of neutrophils. In the absence of T2DM, no significant correlations were found between GDF-15 and the main leukocyte fractions. The results obtained indicate the possible prospect of using the GDF-15 biomarker in a cohort of patients with CHF in combination with T2DM.


Author(s):  
Hadi Bazyar ◽  
Seyed Ahmad Hosseini ◽  
Sirous Saradar ◽  
Delsa Mombaini ◽  
Mohammad Allivand ◽  
...  

Abstract Background In patients with type 2 diabetes mellitus (T2DM) the inflammatory and metabolic responses to epigallocatechin-3-gallate (EGCG) are unknown. Objectives Evaluate the impacts of EGCG on metabolic factors and some biomarkers of stress oxidative in patients with T2DM. Methods In this randomized, double-blind, placebo-controlled trial, 50 patients with T2DM consumed either 2 tablets (300 mg) EGCG (n=25) or wheat flour as placebo (n=25) for 2 months. The total antioxidant capacity (TAC), interleukin-6 (IL-6), lipid profile, mean arterial pressure (MAP), atherogenic index of plasma (AIP) were evaluated before and after the intervention. Results The finding of present study exhibited a significant increase in the serum levels of TAC after the EGCG supplementation (p=0.001). Also, in compare with control group, the mean changes of TAC were significantly higher in supplement group (p=0.01). In intervention group, a significant decrease was observed in the mean levels of triglyceride, total cholesterol, diastolic blood pressure (DBP), AIP, and MAP (p<0.05). Taking EGCG resulted in the mean changes of total cholesterol, MAP and DBP were significantly lower in compare with control group (p<0.05). Conclusions This study recommended that EGCG supplementation may be improved blood pressure, lipid profile, AIP, and oxidative status in patients with T2DM.


Author(s):  
Yangyang Cheng ◽  
Xiaohui Du ◽  
Bilin Zhang ◽  
Junxia Zhang

Abstract Background Serum wnt1-induced signaling pathway protein 1 (WISP1) levels are increased with obesity, which is a common complication associated with lower extremity atherosclerotic disease (LEAD). However, to date, the relationship between elevated WISP1 levels and the incidence of lower extremity atherosclerotic disease (LEAD) in type 2 diabetes mellitus (T2DM) remains unclear. Methods 174 newly diagnosed type 2 diabetic patients were enrolled in our study. Patients were divided into two groups, LEAD group (n=100) and control group (n=74). Anthropometric parameters, blood pressure and some biochemical parameters were obtained. Body composition was detected by bioelectrical impedance analysis (BIA). Levels of serum insulin were determined by radioimmunoassay. Serum WISP1 and interleukin 6 (IL-6) levels were determined using an enzyme-linked immunosorbent assay. Results It was shown that serum WISP1 levels in diabetic patients with LEAD were higher than those without LEAD (P<0.001). Serum WISP1 levels were positively related with waist circumference (r=0.237, P=0.003), waist-hip ratio (r=0.22, P=0.006), visceral fat area (r=0.354, P<0.001), serum creatinine (r=0.192, P=0.012), interleukin 6 (r=0.182, P=0.032), c-reactive protein (r=0.681, P<0.001), triglycerides (r=0.119, P<0.001), fasting glucose (r=0.196, P=0.011), glycated hemoglobin (r=0.284, P<0.001), and HOMA-IR (r=0.285, P<0.026). Compared with the lowest tertile, the odds ratio of the middle tertile for LEAD incidence was 3.27 (95% CI, 1.24–8.64) and 4.46 (95% CI, 1.62–12.29) for the highest tertile after adjusting confounding factors. Conclusion The results suggest that increased serum WISP1 levels independently contribute to the incidence of LEAD in patients with newly diagnosed T2DM.


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