Randomized controlled trial using bosentan to enhance the impact of exercise training in subjects with type 2 diabetes mellitus

Abstract

New Findings r What is the central question of this study?Does the addition of endothelin blockade improve the effect of an 8 week training programme on brachial and superficial femoral artery endothelium-dependent and -independent dilatation and physical fitness in type 2 diabetes patients? r What is the main finding and its importance?Training improved physical fitness but not vascular function in type 2 diabetes. Endothelin blockade had no additional effect on our outcome parameters, suggesting that despite acutely restoring blood flow, endothelin blockade does not potentiate the effect of training on vasculature or fitness in type 2 diabetes.In type 2 diabetes patients, endothelin (ET) receptor blockade may enhance blood flow responses to exercise training. The combination of exercise training and ET receptor blockade may represent a more potent stimulus than training alone to improve vascular function, physical fitness and glucose homeostasis. We assessed the effect of an 8 week exercise training programme combined with either ET blockade or placebo on vasculature, fitness and glucose homeostasis in people with type 2 diabetes. In a double-blind randomized controlled trial, brachial endothelium-dependent and -independent dilatation (using flow-mediated dilatation and glyceryl trinitrate, respectively), glucose homeostasis (using Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)) and physical fitness (maximal cycling test) were assessed in 18 men with type 2 diabetes (60 ± 6 years old). Subjects underwent an 8 week exercise training programme, with half of the subjects receiving ET receptor blockade (bosentan) and the other half a placebo, followed by reassessment of the tests above. Exercise training improved physical fitness to a similar extent in both groups, but we did not detect changes in vascular function in either group. This study suggests that there is no adaptation in brachial and femoral artery endothelial function after 8 weeks of training in type 2 diabetes patients. Endothelin receptor

The effects of exercise on vascular endothelial function in type 2 diabetes: a systematic review and meta-analysis

“…Of these, 19 articles were excluded; two articles were duplicate [ 22 , 23 ], one measured FMD of popliteal artery [ 24 ], two had patients with different kinds of diseases as well as T2D in the groups [ 25 , 26 ], three had T2D patients with peripheral arterial disease or diabetic peripheral neuropathy [ 27 – 29 ], two did not provide precise data [ 30 , 31 ], two additionally treated dietary control for weight loss [ 32 , 33 ], three involved unstructured or unsupervised exercise intervention [ 34 – 36 ], and four were just abstracts with incomplete data [ 37 – 40 ]. Four exercise groups (EX) with additional interventions were included after discussing because there was no difference in the effect of interventions on FMD, our major outcome, between the CON and experimental groups: (i) exercise in the hypoxic environment (16.5% O 2 , 2000 m) [ 41 ]; (ii) endothelin (ET) receptor blockade or a placebo [ 42 ]; (iii) walking meditation [ 43 ]. One AE trial which recorded the time, frequency, and intensity of exercise by a multi-record accelerometer were also included because the subjects visited the laboratory every 1 or 2 weeks [ 44 ].…”

Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

“…In patients with type 2 diabetes, exercise training was reported to improve brachial artery endothelial function (91), as well as to attenuate capillary rarefaction and improve microvascular vasodilator and insulin signaling (92). In contrast, Schreuder et al (93) did not find any improvement in endothelial function after 8 weeks of training in type 2 diabetes patients. Although a reasonable supposition, there is insufficient data to assess whether dietary and lifestyle changes offer real promise to human sufferers of HFpEF.…”

Research Article Improvement of Exercise Intervention on Vascular Endothelial Functions during Prediabetes Mellitus

“…The American College of Sport Medicine and the American Diabetes Association only provide universal exercise programs for diabetic patients in their issued joint statements, and recommend aerobic exercise or aerobic plus resistance exercise to reduce the risk of cardiovascular disease in patients with diabetes (Albright et al, 2000;Colberg et al, 2010). However, some studies indicate positive effect of exercise on vascular endothelial function (Maiorana et al, 2001;De Filippis et al, 2006;Okada et al, 2010;Mitranun et al, 2014), while others may be ineffective for diabetic patients (Miche et al, 2006;Middlebrooke et al, 2006;Schreuder et al, 2014). A few researches present exercise intervention can improve vascular endothelial dysfunction in individuals with metabolic syndrome (Tjønna et al, 2008;Vinet et al, 2015).…”