Association of the polymorphism in the androgen receptor gene and endothelial function in men with type 2 diabetes

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.

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Lipid metabolism and production of incretins in patients with obesity and type 2 diabetes mellitus after biliopancreatic diversion in Hess-Marceau modification at the early stages of follow-up

Obesity and metabolism ◽

10.14341/omet2016338-44 ◽

2016 ◽

Vol 13 (3) ◽

pp. 38-44

Author(s):

Ekaterina Ershova ◽

Ekaterina Troshina ◽

Yury Yashkov

Keyword(s):

Type 2 Diabetes ◽

Lipid Metabolism ◽

Total Cholesterol ◽

Biliopancreatic Diversion ◽

Positive Impact ◽

Positive Association ◽

Hdl Cholesterol ◽

Atherogenic Index ◽

Number Of Patients

Objectives: To study the lipid metabolism and secretion of GLP-1 and GIP in obese patients with type 2 diabetes before and 3 months after biliopancreatic diversion (BPD) in Hess-Marceau modification.Materials and methods: 22 patients (44 [38.0; 55.0] years) with morbid obesity (BMI of 50.1 [41.3; 53.8]) and type 2 diabetes were included in the study. Total cholesterol, LDL-C, HDL-C, TG, GLP-1, GIP were evaluated before and 3 months after BPD.Results: At 3 months after BPD there were decreases in weight by 15.8% and a reduction in total cholesterol levels and LDL-C, an increase in the number of patients with a target value of total cholesterol and LDL-C (from 4/22 (18%) to 20/22 (91%, p = 0.0001)). TG levels during the first 3 months after BPD did not change, but there was a trend to an increase in the number of patients with TG target levels (from 8/22 (32%) to 15/22 (68%, p = 0.058)). Due to the reduction of total cholesterol intake after malabsorbtive surgery, we saw a regular decrease in HDL-cholesterol. 3 months after BPD there was an increase in basal secretion of GLP-1 and GIP as compared to preoperative levels, and a strong positive association of the basal GIP with the HDL-C (r = 0,8, p = 0.007) and a strong negative association – with the atherogenic index (r = – 0,7, p = 0.009) at 3 weeks after surgery.Conclusions: The majority of patients with obesity and type 2 diabetes as early as at 3 months after BPD in the modification by Hess-Marceau achieve a significant improvement in the parameters of lipid metabolism; expect positive impact of the GIP on lipid metabolism.

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The epifamin effect on values of immune status, carbohydrate and lipid metabolism in the patients with non-alcoholic steatohepatitis developing at type 2 diabetes mellitus

Journal of New Medical Technologies eJournal ◽

10.12737/5038 ◽

2014 ◽

Vol 8 (1) ◽

pp. 1-7

Author(s):

Золоедов ◽

V. Zoloedov ◽

Агарков ◽

A. Agarkov ◽

Попов ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Lipid Metabolism ◽

Immune Status ◽

Atherogenic Index ◽

Alcoholic Steatohepatitis ◽

Carbohydrate And Lipid Metabolism ◽

Basic Treatment

The study is devoted to the Epifamin effect on values of carbohydrate and lipid metabolism, immune status in blood, and also content of 6-sulfatohymelatonin as the main metabolite of melatonin, in urine of the patients with non-alcoholic steatohepatitis developing at type 2 diabetes mellitus. It is shown that fasting glucose, postprandial glucose level and glycated hemoglobin content in the blood of patients decreased significantly during combined treatment with the Epifamin compared to the basic therapy. The results of the Epifamin reception are as follows: more expressed normalization of lipid metabolism, and content of β -lipoproteins, cholesterol, lipoproteins of low density and high density lipoprotein, and atherogenic index in comparison with the results obtained after basic treatment. The obtained results testify to positive Epifamin effect on values of the immune status of patients: level of circulating immune complexes, the main classes of immunoglobulins – IgA, IgM, IgG. It was established that in the patients with non-alcoholic steatohepatitis developing at type 2 diabetes mellitus, 6-sulfatohymelatonin level in urine was lowered on the average by 1,2 times in comparison with control. After basic treatment the reliable changes of the 6-sulfatohymelatonin content in the patients didn’t reveal. After the combined therapy with the Epifamin, the 6-sulfatohymelatonin content in the patients increased on the average for 13.9%. The obtained results allow to conclude about correction the Epifamin effect on melatonin content as a hormone, which able to participate in regulation of carbohydrate and lipid metabolism and to have immune modulating action. The Epifamin use in basic treatment had favorable influence on the immune status, values of carbohydrate and lipid metabolism in blood in the patients with non-alcoholic steatohepatitis developing at type 2 diabetes mellitus that was apparently due to melatonin-corrective effect of this drug.

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Elevation in blood flow and shear rate prevents hyperglycemia-induced endothelial dysfunction in healthy subjects and those with type 2 diabetes

Journal of Applied Physiology ◽

10.1152/japplphysiol.00936.2014 ◽

2015 ◽

Vol 118 (5) ◽

pp. 579-585 ◽

Cited By ~ 14

Author(s):

Arno Greyling ◽

Tim H. A. Schreuder ◽

Thijs Landman ◽

Richard Draijer ◽

Rebecca J. H. M. Verheggen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Flow ◽

Shear Rate ◽

Endothelial Function ◽

Brachial Artery ◽

Interaction Effect ◽

Healthy Subjects ◽

Local Heating ◽

Oral Glucose

Hyperglycemia, commonly present after a meal, causes transient impairment in endothelial function. We examined whether increases in blood flow (BF) protect against the hyperglycemia-mediated decrease in endothelial function in healthy subjects and patients with type 2 diabetes mellitus (T2DM). Ten healthy subjects and 10 age- and sex-matched patients with T2DM underwent simultaneous bilateral assessment of brachial artery endothelial function by means of flow-mediated dilation (FMD) using high-resolution echo-Doppler. FMD was examined before and 60, 120, and 150 min after a 75-g oral glucose challenge. We unilaterally manipulated BF by heating one arm between minute 30 and minute 60. Oral glucose administration caused a statistically significant, transient increase in blood glucose in both groups ( P < 0.001). Forearm skin temperature, brachial artery BF, and shear rate significantly increased in the heated arm ( P < 0.001), and to a greater extent compared with the nonheated arm in both groups (interaction effect P < 0.001). The glucose load caused a transient decrease in FMD% ( P < 0.05), whereas heating significantly prevented the decline (interaction effect P < 0.01). Also, when correcting for changes in diameter and shear rate, we found that the hyperglycemia-induced decrease in FMD can be prevented by local heating ( P < 0.05). These effects on FMD were observed in both groups. Our data indicate that nonmetabolically driven elevation in BF and shear rate can similarly prevent the hyperglycemia-induced decline in conduit artery endothelial function in healthy volunteers and in patients with type 2 diabetes. Additional research is warranted to confirm that other interventions that increase BF and shear rate equally protect the endothelium when challenged by hyperglycemia.

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Evaluation of brachial artery diameter and flow-mediated vasodilatation as tools to predict cardiovascular events in type 2 diabetes patients

Diabetology & Metabolic Syndrome ◽

10.1186/1758-5996-7-s1-a40 ◽

2015 ◽

Vol 7 (S1) ◽

Author(s):

Lorenzo Catucci Boza ◽

Cristine Kasmirscki ◽

Sandro Antunes da Silva ◽

Maira Zoldan ◽

Thiago Barth Bertotto ◽

...

Keyword(s):

Type 2 Diabetes ◽

Brachial Artery ◽

Cardiovascular Events ◽

Brachial Artery Diameter ◽

Diabetes Patients

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

Clinical Science ◽

10.1042/cs20191227 ◽

2020 ◽

Vol 134 (17) ◽

pp. 2369-2379

Author(s):

Joshua A. Beckman ◽

Jiun-Ruey Hu ◽

Shi Huang ◽

Eric Farber-Eger ◽

Quinn S. Wells ◽

...

Keyword(s):

Type 2 Diabetes ◽

Brachial Artery ◽

Vascular Function ◽

Glyoxylic Acid ◽

Muscle Metabolism ◽

Plasma Metabolites ◽

Brachial Artery Diameter ◽

The Impact ◽

Ischemic Stress

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.

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Effect of empagliflozin on brachial artery shear stress and endothelial function in subjects with type 2 diabetes: Results from an exploratory study

Diabetes and Vascular Disease Research ◽

10.1177/1479164119883540 ◽

2019 ◽

Vol 17 (1) ◽

pp. 147916411988354 ◽

Cited By ~ 2

Author(s):

Concetta Irace ◽

Antonio Cutruzzolà ◽

Martina Parise ◽

Raffaella Fiorentino ◽

Marco Frazzetto ◽

...

Keyword(s):

Type 2 Diabetes ◽

Shear Stress ◽

Endothelial Function ◽

Brachial Artery ◽

Therapy Group ◽

Glycated Haemoglobin ◽

Flow Mediated Dilation ◽

Endothelial Surface ◽

Significant Difference

Empagliflozin reduces the risk of cardiovascular mortality in subjects with type 2 diabetes. We demonstrated that empagliflozin increases blood viscosity and carotid shear stress and decreases carotid wall thickness. Shear stress is the force acting on the endothelial surface and modulates arterial function. The current study evaluates the influence of empagliflozin on brachial artery shear stress and endothelial function compared to incretin-based therapy. The study is a nonrandomized, open, prospective cohort study including 35 subjects with type 2 diabetes administered empagliflozin or incretin-based therapy. Shear stress was calculated with a validated formula, and endothelial function was evaluated using the flow-mediated dilation technique. Both treatments resulted in comparable reductions in blood glucose and glycated haemoglobin. Brachial artery shear stress significantly increased exclusively in the empagliflozin group (61 ± 20 vs 68 ± 25 dynes/cm2, p = 0.04), whereas no significant difference was detected in the incretin-based therapy group (60 ± 20 vs 55 ± 12 dynes/cm2, p = not significant). Flow-mediated dilation significantly increased in the empagliflozin group (4.8 ± 4.5% vs 8.5 ± 5.6%, p = 0.03). Again, no change was detected in the incretin-based therapy group (5.1 ± 4.5% vs 4.7 ± 4.7%, p = not significant). The present findings demonstrate the beneficial effect of empagliflozin on shear stress and endothelial function in subjects with type 2 diabetes independent of the hypoglycaemic effect.

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