scholarly journals Metabolomics reveals the impact of Type 2 diabetes on local muscle and vascular responses to ischemic stress

2020 ◽  
Vol 134 (17) ◽  
pp. 2369-2379
Author(s):  
Joshua A. Beckman ◽  
Jiun-Ruey Hu ◽  
Shi Huang ◽  
Eric Farber-Eger ◽  
Quinn S. Wells ◽  
...  

Abstract Objective: Type 2 diabetes mellitus (T2DM) reduces exercise capacity, but the mechanisms are incompletely understood. We probed the impact of ischemic stress on skeletal muscle metabolite signatures and T2DM-related vascular dysfunction. Methods: we recruited 38 subjects (18 healthy, 20 T2DM), placed an antecubital intravenous catheter, and performed ipsilateral brachial artery reactivity testing. Blood samples for plasma metabolite profiling were obtained at baseline and immediately upon cuff release after 5 min of ischemia. Brachial artery diameter was measured at baseline and 1 min after cuff release. Results: as expected, flow-mediated vasodilation was attenuated in subjects with T2DM (P<0.01). We confirmed known T2DM-associated baseline differences in plasma metabolites, including homocysteine, dimethylguanidino valeric acid and β-alanine (all P<0.05). Ischemia-induced metabolite changes that differed between groups included 5-hydroxyindoleacetic acid (healthy: −27%; DM +14%), orotic acid (healthy: +5%; DM −7%), trimethylamine-N-oxide (healthy: −51%; DM +0.2%), and glyoxylic acid (healthy: +19%; DM −6%) (all P<0.05). Levels of serine, betaine, β-aminoisobutyric acid and anthranilic acid were associated with vessel diameter at baseline, but only in T2DM (all P<0.05). Metabolite responses to ischemia were significantly associated with vasodilation extent, but primarily observed in T2DM, and included enrichment in phospholipid metabolism (P<0.05). Conclusions: our study highlights impairments in muscle and vascular signaling at rest and during ischemic stress in T2DM. While metabolites change in both healthy and T2DM subjects in response to ischemia, the relationship between muscle metabolism and vascular function is modified in T2DM, suggesting that dysregulated muscle metabolism in T2DM may have direct effects on vascular function.

2015 ◽  
Vol 18 (4) ◽  
pp. 35-40 ◽  
Author(s):  
Irina Alekseevna Khripun ◽  
Sergey Vladislavovich Vorobyev ◽  
Michael Iosifovich Kogan

In recent years, actively studied the effect of androgen deficiency on the cardiovascular system, including endothelial function. Genomic effects of testosterone caused by the length of CAG repeats polymorphism in the androgen receptor (AR) gene.Aim. To examine the association of the polymorphism in the AR gene and carbohydrate, lipid metabolism, endothelial function in men with type 2 diabetes.Materials and methods. We examined 88 men, aged 40-65 years (mean age 53±6,4years) with type 2 diabetes. All patients underwent the study of carbohydrate and lipid metabolism, the assessment of vasomotor endothelial function of the brachial artery by ultrasound sonography, were studied biochemical markers of endothelial dysfunction – ICAM-1, VCAM-1, p-selectin, e-selectin, resistin and number of CAG-repeats in the AR gene. Statistical analysis was performed using the application package SPSS 21,0 using regression analysis.Results. The number of CAG repeats had a significant positive regression to the level of total testosterone, a weak negative regression of the number of CAG repeats in the AR gene and lipid metabolism: triglycerides, LDL, atherogenic index. The assessment of the brachial artery ultrasonography revealed negative regression of the baseline brachial artery diameter and blood flow velocity in the endothelium-dependent vasodilation. The number of CAG repeats was significantly correlated with the levels of p-selectin and resistin. Thus, increasing the number of CAG repeats in the AR gene via a weakening of sensitivity to androgens leads to disruption of endothelial function in men with type 2 diabetes. Increasing the number of CAG repeats in the AR gene leads to deterioration of linear flow velocity during the test with reactive hyperemia with increasing production of p-selectin and resistin.Conclusions. The number of CAG repeats in the AR gene can be regarded as a predictor of the development and progression of cardiovascular lesions in men with type 2 diabetes.


2008 ◽  
Vol 295 (4) ◽  
pp. H1594-H1598 ◽  
Author(s):  
Dick H. J. Thijssen ◽  
Marieke M. van Bemmel ◽  
Lauren M. Bullens ◽  
Ellen A. Dawson ◽  
Nicola D. Hopkins ◽  
...  

Flow-mediated dilation (FMD) has become a commonly applied approach for the assessment of vascular function and health, but methods used to calculate FMD differ between studies. For example, the baseline diameter used as a benchmark is sometimes assessed before cuff inflation, whereas others use the diameter during cuff inflation. Therefore, we compared the brachial artery diameter before and during cuff inflation and calculated the resulting FMD in healthy children ( n = 45; 10 ± 1 yr), adults ( n = 31; 28 ± 6 yr), and older subjects ( n = 22; 58 ± 5 yr). Brachial artery FMD was examined after 5 min of distal ischemia. Diameter was determined from either 30 s before cuff inflation or from the last 30 s during cuff inflation. Edge detection and wall tracking of high resolution B-mode arterial ultrasound images was used to calculate conduit artery diameter. Brachial artery diameter during cuff inflation was significantly larger than before inflation in children ( P = 0.02) and adults ( P < 0.001) but not in older subjects ( P = 0.59). Accordingly, FMD values significantly differed in children (11.2 ± 5.1% vs. 9.4 ± 5.2%; P = 0.02) and adults (7.3 ± 3.2% vs. 4.6 ± 3.3%; P < 0.001) but not in older subjects (6.3 ± 3.4% vs. 6.0 ± 4.2%; P = 0.77). When the diameter before cuff inflation was used, an age-dependent decline was evident in FMD, whereas FMD calculated using the diameter during inflation was associated with higher FMD values in older than younger adults. In summary, the inflation of the cuff significantly increases brachial artery diameter, which results in a lower FMD response. This effect was found to be age dependent, which emphasizes the importance of using appropriate methodology to calculate the FMD.


2020 ◽  
Vol 26 (46) ◽  
pp. 5980-5987
Author(s):  
Stavroula A. Paschou ◽  
Gerasimos Siasos ◽  
Evanthia Bletsa ◽  
Panagiota K. Stampouloglou ◽  
Evangelos Oikonomou ◽  
...  

: We systematically reviewed the literature regarding the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on vascular function, including endothelial function and arterial stiffness, as predictors of atherosclerosis progression and cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). We searched PubMed in order to identify clinical trials that investigated the effect of DPP-4i on vascular function in patients with T2DM when compared with placebo. Although 168 articles were initially found, only 6 studies (total 324 patients) investigated the effect of DPP-4i in comparison with placebo, specifically linagliptin and sitagliptin, and satisfied the inclusion criteria. There are scarce data to indicate that linagliptin may enhance endothelial function and exert a slight beneficial effect on arterial wall properties. Sitagliptin seems to have a neutral effect on these variables. Further trials are needed to elucidate the topic. The standards of reporting were in accordance with the PRISMA guidelines.


2015 ◽  
Vol 7 (S1) ◽  
Author(s):  
Lorenzo Catucci Boza ◽  
Cristine Kasmirscki ◽  
Sandro Antunes da Silva ◽  
Maira Zoldan ◽  
Thiago Barth Bertotto ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1612-P
Author(s):  
NADIRA SULTANA KAKOLY ◽  
ARUL EARNEST ◽  
HELENA TEEDE ◽  
LISA MORAN ◽  
DEBORAH LOXTON ◽  
...  

Author(s):  
Larisa Dmitrievna Popovich ◽  
Svetlana Valentinovna Svetlichnaya ◽  
Aleksandr Alekseevich Moiseev

Diabetes – a disease in which the effect of the treatment substantially depends on the patient. Known a study showed that the use of glucometers with the technology of three-color display of test results facilitates self-monitoring of blood sugar and leads to a decrease in glycated hemoglobin (HbAlc). Purpose of the study: to modeling the impact of using of a glucometer with a color-coded display on the clinical outcomes of diabetes mellitus and calculating, the potential economic benefits of reducing the hospitalization rate of patients with diabetes. Material and methods. Based on data from two studies (O. Schnell et al. and M. Baxter et al.) simulation of the reduction in the number of complications with the use of a glucometer with a color indication. In a study by O. Schnell et al. a decrease of HbA1c by 0.69 percent is shown when using the considered type of glucometers, which was the basis of the model. Results. In the model, the use of a glucometer with a color-coded display for type 1 diabetes led to a decrease in the total number of complications by 9.2 thousand over 5 years per a cohort of 40 thousand patients with different initial levels of HbA1c. In a cohort of 40 thousand patients with type 2 diabetes, the simulated number of prevented complications was 1.7 thousand over 5 years. When extrapolating these data to all patients with diabetes included in the federal register of diabetes mellitus (FRD), the number of prevented complications was 55.4 thousand cases for type 1 diabetes and 67.1 thousand cases for type 2 diabetes. The possible economic effect from the use of the device by all patients with a diagnosis of diabetes, which are included in the FRD, estimated at 1.5 billion rubles for a cohort of patients with type 1 diabetes and 5.3 billion rubles for patients with type 2 diabetes. Conclusion. Improving the effectiveness of self-monitoring, which is the result of the use of glucometers with color indicators, can potentially significantly reduce the incidence of complications in diabetes and thereby provide significant economic benefits to society.


2011 ◽  
Vol 7 (3) ◽  
pp. 185-189 ◽  
Author(s):  
Richdeep S. Gill ◽  
Arya M. Sharma ◽  
David P. Al-Adra ◽  
Daniel W. Birch ◽  
Shahzeer Karmali

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