scholarly journals Urinary Leukotriene E4Is Associated with Renal Function but Not with Endothelial Function in Type 2 Diabetes

2013 ◽  
Vol 35 ◽  
pp. 475-480 ◽  
Author(s):  
Arnar Rafnsson ◽  
Magnus Bäck

Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4(U-LTE4) is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65) with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR) of 71 (14–129) mL/min. Reactive hyperemia index (RHI) was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD). Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4was correlated with serum creatinine (R=−0.572;P=0.001) and eGFR (R=0.517;P=0.0036). A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4concentrations. In conclusion, the present results did not establish an association of U-LTE4with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Ping Song ◽  
Jin Xu ◽  
Yongfeng Song ◽  
Shiliang Jiang ◽  
Haitao Yuan ◽  
...  

Aims. This study aimed to investigate whether the change of plasma myeloperoxidase (MPO) level would be associated with the incidence of coronary artery disease (CAD) among diabetic patients.Methods. 339 patients with type 2 diabetes mellitus (DM) underwent coronary angiography. Of them, 204 cases had CAD and were assigned to CAD group and 135 cases without CAD were assigned to non-CAD group.Results. Compared to non-CAD group, CAD group had higher level of plasma MPO (p<0.01). Multiple linear regression analysis showed that plasma MPO level was correlated with Gensini score. Multiple logistic analysis showed that the odds ratios for CAD across increasing tertiles of MPO level were 1.191 (0.971–1.547) and 1.488 (1.115–2.228) (p=0.048,p=0.009versus 1st tertile of MPO level, resp.) by adjusting for age, sex, and other conventional risk factors for CAD. The subjects were stratified into nine groups according to tertiles of MPO and HbA1c. The odds ratio for CAD was significantly higher in group with highest levels of MPO and HbA1c (OR = 4.08,p<0.01).Conclusion. Plasma MPO level was positively correlated with the degree of coronary artery stenosis in type 2 diabetic patients, and increasing blood glucose might amplify the association between MPO and CAD.


2014 ◽  
Vol 99 (11) ◽  
pp. E2330-E2334 ◽  
Author(s):  
Tianpeng Zheng ◽  
Yun Gao ◽  
Attit Baskota ◽  
Tao Chen ◽  
Xingwu Ran ◽  
...  

Context: The significance of associations between prediabetes, type 2 diabetes, and dipeptidyl peptidase-4 (DPP4) activity in a Chinese population is not clear. Objective: The objective of the study was to determine whether DPP4 activity and active glucagon-like peptide-1 (GLP-1) were predictive of the onset of prediabetes and type 2 diabetes. Design, Setting, and Patients: This was a 4-year follow-up study conducted in Sichuan, China. A total of 474 Chinese women and men aged 18–70 years were studied. Main Outcome Measures: All subjects were divided into 3 groups (normal glucose tolerance, prediabetes, and type 2 diabetes) on the basis of their glucose metabolism status after 4 years. The DPP4 activity, active GLP-1, and glucagon were measured at baseline and 4 years later. Results: The baseline DPP4 activity was significantly higher in subjects who had progressed to prediabetes or type 2 diabetes compared with subjects who remained normoglycemic (P &lt; .01). In a multiple linear regression analysis, baseline DPP4 activity and active GLP-1 were independent predictors of an increase in insulin resistance over a 4-year period (P &lt; .05). Cox proportional hazards models revealed that DPP4 activity independently predicted the risk of developing prediabetes [relative risk 2.77 (95% confidence interval 1.38–5.55), P &lt; .01] and type 2 diabetes [5.10 (95% confidence interval 1.48–17.61), P &lt; .05] after adjustment for confounding risk factors. Conclusions: DPP4 activity is an important predictor of the onset of insulin resistance, prediabetes, and type 2 diabetes in apparently healthy Chinese individuals. This finding may have important implications for understanding the etiology of diabetes.


2016 ◽  
Vol 19 (5) ◽  
pp. 383-387 ◽  
Author(s):  
Irina Alexandrovna Khripun ◽  
Sergey Vladislavovich Vorobyev ◽  
Maxim Nikolaevich Morgunov ◽  
Michail Iosifovich Kogan

Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease that is based on endothelial dysfunction (ED). Currently, conventional diagnostic methods are unreliable, especially at early stages of disease.Aims. The aim of this work was to assess endothelial function in men with T2DM without clinical signs of cardiovascular disease.Materials and methods. The study included 100 patients (mean age, 54.3 ± 5.3 years) with a T2DM duration of less than 10 years and without signs of cardiovascular disease. The patients were divided into two groups: group 1 consisted of 60 patients with a T2DM duration of less than five years. Group 2 included 40 men with a history of diabetes between 5 and 10 years. Endothelial function was assessed by the levels of nitric oxide (NO), endothelial NO synthase type 3 (eNOS3), ICAM-1, VCAM-1, E-selectin, P-selectin, resistin and C-reactive protein and the arterial vasoreactivity of the brachial artery (BA) using the D. Celermajer method.Results. Results revealed decreases in levels of both eNOS3 by 2.5 fold (P = 0.0005) and NO by 1.9 fold (P = 0.043) in group 2 patients, compared to those in group 1 patients. When the duration of diabetes was greater than five years, levels of VCAM-1, resistin and C-reactive protein increased by 12.1% (P = 0.048), 62% (P = 0.01) and 45.6%, respectively. Additionally, the time until maximal BA vasodilatation during reactive hyperemia was observed to be higher in group 2 [105 (90; 180) seconds] than those in group 1 [90 (60; 120) seconds].Conclusions. Biochemical and imaging signs of ED begin to appear in the first five years of T2DM, long before clinical manifestations. The earliest symptoms are decreases in eNOS3 and NO levels, increases in VCAM-1 and resistin concentrations and increased time until maximal BA vasodilatation during reactive hyperemia.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Huili Wei ◽  
Hua Qu ◽  
Hang Wang ◽  
Huacong Deng

Aims. To detect the association of C1q/TNF-related protein-3 (CTRP-3) and high-mobility group box-1 (HMGB-1) in subjects with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (nT2DM).Methods. 224 eligible participants were included. The 75 g oral glucose tolerance test (OGTT) and several clinical parameters of metabolic disorders and cytokines were measured. All participants were divided into three groups: normal glucose tolerance (NGT,n=62), pre-DM (n=111), and nT2DM group (n=56).Results. Plasma CTRP-3 concentrations were significantly lower in subjects with pre-DM and nT2DM than that of the NGT group, while plasma HMGB-1 levels were higher in pre-DM and nT2DM group compared with the NGT group (P<0.05). A multiple linear regression analysis showed both plasma CTRP-3 and HMGB-1 concentrations were independently associated with homeostasis model assessment for insulin resistance (HOMA-IR) and interleukin-6 (IL-6) (P<0.05for all). Further multiple logistical regression analyses revealed that both plasma CTRP-3 and HMGB-1 levels were significantly associated with pre-DM and nT2DM after adjusting for several confounders (P<0.001for all).Conclusions. Circulating CTRP-3 and HMGB-1 concentrations might be promising biomarkers to predict prediabetes and type 2 diabetes.


Author(s):  
Melissa K Thomas ◽  
Amir Nikooienejad ◽  
Ross Bray ◽  
Xuewei Cui ◽  
Jonathan Wilson ◽  
...  

Abstract Context Novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide. Objective Explore mechanisms of glucose control by tirzepatide. Design Post hoc analyses of fasting biomarkers and multiple linear regression analysis. Setting Forty-seven sites in 4 countries. Patients or other Participants Three hundred and sixteen subjects with type 2 diabetes. Interventions Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo. Main Outcome Measures Analyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks. Results Homeostatic model assessment (HOMA) 2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (P ≤ .02). Proinsulin/insulin and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (P ≤ .007). Tirzepatide 10 and 15 mg significantly decreased fasting insulin (P ≤ .033) and tirzepatide 10 mg significantly decreased HOMA2-IR (P = .004) compared with placebo and dulaglutide. Markers of improved insulin sensitivity (IS) adiponectin, IGFBP-1, and IGFBP-2 significantly increased by 1 or more doses of tirzepatide (P &lt; .05). To determine whether improvements in IR were directly attributable to WL, multiple linear regression analysis with potential confounding variables age, sex, metformin, triglycerides, and glycated hemoglobin A1c was conducted. WL significantly (P ≤ .028) explained only 13% and 21% of improvement in HOMA2-IR with tirzepatide 10 and 15 mg, respectively. Conclusions Tirzepatide improved markers of IS and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to WL, suggesting dual receptor agonism confers distinct mechanisms of glycemic control.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jingcheng Wu ◽  
Xiaohua Li ◽  
Yang Tao ◽  
Yufei Wang ◽  
Yongde Peng

Objective. To investigate the association of thyroid function and diabetic nephropathy (DN) in euthyroid patients with type 2 diabetes.Methods. A total of 421 patients were included in this cross-sectional study. The following parameters were assessed: anthropometric measurements, fast plasma glucose, serum creatinine, lipid profile, HbA1c, free triiodothyronine (FT3), free thyroxine, thyroid-stimulating hormone levels, and urinary albumin-to-creatinine ratio (UACR). Patients with UACR of ≥30 mg/g were defined as those suffering from DN.Results. Of the 421 patients, 203 (48.2%) suffered from DN, and no difference was found between males and females. The patients with DN yielded significantly lower FT3 levels than those without DN (P<0.01). The prevalence of DN showed a significantly decreasing trend across the three tertiles based on FT3 levels (59.6%, 46.4%, and 38.6%,P<0.01). After adjustment for gender and age, FT3 levels were found to correlate positively with estimated glomerular filtration rate (P=0.03) and negatively with UACR (P<0.01). Multiple linear regression analysis showed that FT3 level was independently associated with UACR (β=-0.18,t=-3.70, andP<0.01).Conclusion. Serum FT3 levels are inversely associated with DN in euthyroid patients with type 2 diabetes, independent of traditional risk factors.


2012 ◽  
Vol 32 (2) ◽  
pp. 149-158 ◽  
Author(s):  
Seung Hyeok Han ◽  
Sang Choel Lee ◽  
Ea Wha Kang ◽  
Jung Kyung Park ◽  
Hyang Sook Yoon ◽  
...  

♦BackgroundEndothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD).♦MethodsThis was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia.♦ResultsIn patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 - 9.64) vs 0.48 (0 - 3.89) mL/min/1.73 m2, P = 0.026]. Correlation analyses revealed that residual GFR (p = 0.381, P = 0.001) and total Kt/V urea (γ= 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = -0.351, P = 0.003), high-sensitivity C-reactive protein (p = -0.345, P = 0.003), pulse pressure (γ = -0.341, P = 0.003), and age (γ = -0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017).♦ ConclusionThis study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.


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