BackgroundExercise, when performed on a regular basis, is a well-accepted strategy to improve vascular function in patients with type 2 diabetes. However, the exercise intensity that yields maximal adaptations on structural and functional indices in patients with type 2 diabetes remains uncertain. Our objective was to analyze the impact of a 1-year randomized controlled trial of combined high-intensity interval training (HIIT) with resistance training (RT) vs. a combined moderate continuous training (MCT) with RT on structural and functional arterial indices in patients with type 2 diabetes.MethodsPatients with type 2 diabetes (n = 80) were randomized into an exercise intervention with three groups: control, combined HIIT with RT and combined MCT with RT. The 1-year intervention had 3 weekly exercise sessions. High-resolution ultrasonography of the common carotid artery and central and peripheral applanation tonometry were used to assess the changes in structural and functional arterial indices. Generalized estimating equations were used to model the corresponding outcomes.ResultsAfter adjusting the models for sex, baseline moderate-to-vigorous physical activity, and mean arterial pressure changes, while using the intention-to-treat analysis, a significant interaction was observed on the carotid intima-media thickness (cIMT) for both the MCT (β = − 4.25, p < 0.01) and HIIT group (β = − 3.61, p < 0.01). However, only the HIIT observed favorable changes from baseline to 1-year on peripheral arterial stiffness indices such as carotid radial arterial pulse wave velocity (β = − 0.10, p = 0.044), carotid to distal posterior tibial artery pulse wave velocity (β = − 0.14, p < 0.01), and on the distensibility coefficient (β = − 0.00, p < 0.01). No effect was found for hemodynamic variables after the intervention.ConclusionsFollowing a 1-year intervention in patients with type 2 diabetes, both the MCT and HIIT group reduced their cIMT, whereas only the HIIT group improved their peripheral arterial stiffness indices and distensibility coefficient. Taken together, HIIT may be a meaningful tool to improve long-term vascular complications in type 2 diabetes.Trial registration clinicaltrials.gov ID: NCT03144505

Background Exercise is a well-accepted strategy to improve lipid and inflammatory profile in individuals with type 2 diabetes (T2DM). However, the exercise intensity having the most benefits on lipids and inflammatory markers in patients with T2DM remains unclear. We aimed to analyse the impact of a 1-year combined high-intensity interval training (HIIT) with resistance training (RT), and a moderate continuous training (MCT) with RT on inflammatory and lipid profile in individuals with T2DM. Methods Individuals with T2DM (n = 80, aged 59 years) performed a 1-year randomized controlled trial and were randomized into three groups (control, n = 27; HIIT with RT, n = 25; MCT with RT, n = 28). Exercise sessions were supervised with a frequency of 3 days per week. Inflammatory and lipid profiles were measured at baseline and at 1-year follow-up. Changes in inflammatory and lipid markers were assessed using generalized estimating equations. Results After adjusting for sex, age and baseline moderate-to-vigorous physical activity (MVPA), we observed a time-by-group interaction for Interleukin-6 (IL-6) in both the MCT with RT (β = − 0.70, p = 0.034) and HIIT with RT (β = − 0.62, p = 0.049) groups, whereas, only the HIIT with RT group improved total cholesterol (β = − 0.03, p = 0.045) and LDL-C (β = − 0.03, p = 0.034), when compared to control. No effect was observed for C-reactive protein (CRP), cortisol, tumour necrosis factor-α (TNF-α), soluble form of the haptoglobin-hemoglobin receptor CD163 (sCD163), triglycerides and HDL-C in both groups (p > 0.05). Conclusions Favorable adaptations on IL-6 were observed in both the HIIT and MCT combined with RT groups following a long-term 1-year exercise intervention in individuals with T2DM. However, only the HIIT with RT prevented further derangement of total cholesterol and LDL-C, when compared to the control group. Therefore, in order to encourage exercise participation and improve inflammatory profile, either exercise protocols may be prescribed, however, HIIT with RT may have further benefits on the lipid profile. Trial registration Clinicaltrials.gov ID: NCT03144505

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Bioelectrical impedance analysis (BIA)-derived phase angle (PhA) has been used to assess cellular health in various populations, but its usefulness as a tool for measuring muscular performance in adult athletes has not been extensively investigated. Our investigation examined the association of whole-body (WB) PhA with muscular performance in 117 adult athletes from different sports and additionally assessed whether regional PhA was a better indicator of muscular performance compared to WB, while accounting for lean soft tissue (LST). Muscular performance was assessed with handgrip strength and countermovement jump power. WB and regional PhA and LST were obtained by BIA and dualenergy x-ray absorptiometry, respectively. Multiple linear regression was used to model outcomes, while adjusting for LST. WB PhA was positively associated with relative power and relative and absolute strength (p < 0.05), irrespective of LST. Regional PhA measures explained similar amounts of variance in absolute and relative power and strength as that of WB PhA after accounting for age, sex, height, and sport type (lower limb adj R 2 = 0.42, 0.60 for power; upper limb adj R 2 = 0.38, 0.74 for strength; WB adj R 2 = 0.44, 0.63 and 0.38, 0.75 for power and strength, respectively). Only upper limb PhA was related with strength (p < 0.05) after accounting for upper limb LST. PhA may have the potential to be used as a marker of functional muscle mass, which is important when it comes to assessing muscular performance of athletes. Regional measures of PhA do not provide a better indicator of regional strength or power when compared to WB PhA.

The role of RANKL-RANK pathway in progesterone-driven mammary carcinogenesis and triple negative breast cancer tumorigenesis has been well characterized. However, and despite evidences of the existence of RANK-positive hormone receptor (HR)positive breast tumors, the implication of RANK expression in HR-positive breast cancers has not been addressed before. Here, we report that RANK pathway affects the expression of cell cycle regulators and decreases sensitivity to fulvestrant of estrogen receptor (ER)-positive (ER+)/HER2-breast cancer cells, MCF-7 and T47D. Moreover, RANK overexpressing cells had a staminal and mesenchymal phenotype, with decreased proliferation rate and decreased susceptibility to chemotherapy, but were more invasive in vivo. In silico analysis of the transcriptome of human breast tumors, confirmed the association between RANK expression and stem cell and mesenchymal markers in ER+HER2-tumors. Importantly, exposure of ER+HER2cells to continuous RANK pathway activation by exogenous RANKL, in vitro and in vivo, induced a negative feedback effect, independent of RANK levels, leading to the downregulation of HR and increased resistance to hormone therapy. These results suggest that ER+HER2-RANK-positive cells may constitute an important reservoir of slow cycling, therapy-resistance cancer cells; and that RANK pathway activation is deleterious in all ER+HER2-breast cancer cells, independently of RANK levels.