David Montero

Refuting the myth of non‐response to exercise training: ‘non‐responders’ do respond to higher dose of training

The prevalence of cardiorespiratory fitness (CRF) non‐response gradually declines in healthy individuals exercising 60, 120, 180, 240 or 300 min per week for 6 weeks. Following a successive identical 6‐week training period but comprising 120 min of additional exercise per week, CRF non‐response is universally abolished. The magnitude of CRF improvement is primarily attributed to changes in haemoglobin mass. The potential for CRF improvement may be present and unveiled with appropriate exercise training stimuli in healthy individuals without exception.

Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training

This study assessed the respective contributions of haematological and skeletal muscle adaptations to any observed improvement in peak oxygen uptake ( V̇O2 peak ) induced by endurance training (ET). V̇O2 peak , peak cardiac output ( Q̇ peak ), blood volumes and skeletal muscle biopsies were assessed prior (pre) to and after (post) 6 weeks of ET. Following the post‐ET assessment, red blood cell volume (RBCV) reverted to the pre‐ET level following phlebotomy and V̇O2 peak and Q̇ peak were determined again. We speculated that the contribution of skeletal muscle adaptations to an ET‐induced increase in V̇O2 peak could be identified when offsetting the ET‐induced increase in RBCV. V̇O2 peak , Q̇ peak , blood volumes, skeletal muscle mitochondrial volume density and capillarization were increased after ET. Following RBCV normalization, V̇O2 peak and Q̇ peak reverted to pre‐ET levels. These results demonstrate the predominant contribution of haematological adaptations to any increase in V̇O2 peak induced by ET.

Vascular smooth muscle function in type 2 diabetes mellitus: a systematic review and meta-analysis

Aims/hypothesisIn type 2 diabetes, in contrast to the well-documented endothelial dysfunction, studies assessing vascular smooth muscle (VSM) function have yielded discrepant results over the last two decades. We therefore sought to determine whether or not VSM function is impaired in individuals with type 2 diabetes.MethodsWe conducted a systematic search of MEDLINE, Cochrane, Scopus and Web of Science databases, from their respective inceptions until December 2012, for articles evaluating VSM function in individuals with type 2 diabetes. A meta-analysis was performed to compare the standardised mean difference (SMD) in VSM function between individuals with type 2 diabetes and age-matched controls. Subgroup analyses and meta-regression were used to identify sources of heterogeneity.ResultsTwenty-seven articles (1,042 individuals with type 2 diabetes and 601 control subjects) were included in this analysis. VSM function was significantly impaired in diabetic compared with control subjects (SMD −0.68, 95% CI −0.84, −0.52; p < 0.001). Although moderate heterogeneity among studies was found (I2 = 52%), no significant publication bias was detected. Subgroup analyses showed a further decline in VSM function assessed in the microcirculation compared with the macrocirculation of individuals with type 2 diabetes (p = 0.009). In meta-regression, VSM function in the microcirculation was inversely associated with BMI and triacylglycerols and was positively associated with HDL-cholesterol.Conclusions/interpretationIn addition to the endothelium, the VSM is a source of vascular dysfunction in type 2 diabetes. An exacerbation of VSM function in the microcirculation may be a distinctive feature in type 2 diabetes.

Endurance Training and V˙o2max: Role of Maximal Cardiac Output and Oxygen Extraction

PURPOSE Although endurance training (ET) commonly augments maximal oxygen consumption (V˙O2max), it remains unclear whether such increase is associated with that of maximal cardiac output (Qmax) alone or along with arteriovenous oxygen difference (a-V˙O2diff). Herein, we sought to systematically review and determine the effects of ET on V˙O2max, Qmax, and a-V˙O2diff at maximal exercise, and on their associations, in healthy young subjects. METHODS We conducted a systematic search of MEDLINE, Scopus, and Web of Science (from their inception until September 2014) for articles assessing the effects of ET lasting ≥3 wk on V˙O2max and Qmax and/or a-V˙O2diff at maximal exercise in healthy young adults (mean age <40 yr). Meta-analyses were performed to determine standardized mean differences (SMD) in V˙O2max, Qmax, and a-V˙O2diff at maximal exercise between posttraining and pretraining measurements. Subgroup and meta-regression analyses were used to evaluate associations among SMD and potential moderating factors. RESULTS Thirteen studies were included after systematic review, comprising a total of 130 untrained or moderately trained healthy young subjects (mean age, 22-28 yr). Duration of ET programs ranged from 5 to 12.9 wk. After data pooling, V˙O2max (SMD = 0.75, P < 0.0001) and Qmax (SMD = 0.64, P < 0.0001), but not a-V˙O2diff at maximal exercise (SMD = 0.21, P = 0.23), were increased after ET. No significant heterogeneity was detected. With meta-regression, the SMD in Qmax was positively associated with the SMD in V˙O2max (B = 0.91, P = 0.007). The SMD in a-V˙O2diff at maximal exercise was not associated with the SMD in V˙O2max (B = 0.20, P = 0.40). CONCLUSIONS Based on a relatively small number of studies, improvement in V˙O2max following 5-13 wk of ET is associated with increase in Qmax, but not in a-V˙O2diff, in previously untrained to moderately trained healthy young individuals.

Acute Hyperglycemia Impairs Vascular Function in Healthy and Cardiometabolic Diseased Subjects Systematic Review and Meta-Analysis

Objectives—Controversy exists over the effect of acute hyperglycemia on vascular function. In this systematic review, we compared the effect of acute hyperglycemia on endothelial and vascular smooth muscle functions across healthy and cardiometabolic diseased subjects. Approach and Results—A systematic search of MEDLINE, EMBASE, and Web of Science from inception until July 2014 identified articles evaluating endothelial or vascular smooth muscle function during acute hyperglycemia and normoglycemia. Meta-analyses compared the standardized mean difference (SMD) in endothelial and vascular smooth muscle functions between acute hyperglycemia and normoglycemia. Subgroup analyses and metaregression identified sources of heterogeneity. Thirty-nine articles (525 healthy and 540 cardiometabolic subjects) were analyzed. Endothelial function was decreased (39 studies; n=1065; SMD, −1.25; 95% confidence interval, −1.52 to −0.98; P<0.01), whereas vascular smooth muscle function was preserved (6 studies; n=144; SMD, −0.07; 95% confidence interval, −0.30 to 0.16; P=0.55) during acute hyperglycemia compared with normoglycemia. Significant heterogeneity was detected among endothelial function studies (P<0.01). A subgroup analysis revealed that endothelial function was decreased in the macrocirculation (30 studies; n=884; SMD, −1.40; 95% confidence interval, −1.68 to −1.12; P<0.01) but not in the microcirculation (9 studies; n=181; SMD, −0.63; 95% confidence interval, −1.36 to 0.11; P=0.09). Similar results were observed according to health status. Macrovascular endothelial function was inversely associated with age, blood pressure, and low-density lipoprotein cholesterol and was positively associated with the postocclusion interval of vascular assessment. Conclusions—To our knowledge, this is the first systematic review and meta-analysis of its kind. In healthy and diseased subjects, we found evidence for macrovascular but not microvascular endothelial dysfunction during acute hyperglycemia.

Biology of VO2max: looking under the physiology lamp

In this review, we argue that several key features of maximal oxygen uptake (VO2max) should underpin discussions about the biological and reductionist determinants of its interindividual variability: (i) training‐induced increases in VO2max are largely facilitated by expansion of red blood cell volume and an associated improvement in stroke volume, which also adapts independent of changes in red blood cell volume. These general concepts are also informed by cross‐sectional studies in athletes that have very high values for VO2max. Therefore, (ii) variations in VO2max improvements with exercise training are also likely related to variations in these physiological determinants. (iii) All previously untrained individuals will respond to endurance exercise training in terms of improvements in VO2max provided the stimulus exceeds a certain volume and/or intensity. Thus, genetic analysis and/or reductionist studies performed to understand or predict such variations might focus specifically on DNA variants or other molecular phenomena of relevance to these physiological pathways.

Flow-Mediated Dilation in Athletes: Influence of Aging.

PURPOSE Controversy exists on whether endothelial function is enhanced in athletes. We sought to systematically review the literature and determine whether endothelial function, as assessed by flow-mediated dilation (FMD), is greater in athletes across all ages relative to that in their age-matched counterparts. METHODS We conducted a systematic search on MEDLINE, Cochrane, Scopus, and Web of Science since their inceptions until July 2013 for articles evaluating FMD in athletes. A meta-analysis was performed to compare the standardized mean difference (SMD) in FMD of the brachial artery between athletes and age-matched control subjects. Subgroup analyses and meta-regression were used to identify sources of heterogeneity. RESULTS Twenty-one articles were included in this analysis, comprising 530 athletes (452 endurance trained, 49 strength trained, and 29 endurance and strength trained) and 376 control subjects. After data pooling, FMD was higher in athletes than that in control groups (SMD, 0.48; P = 0.008). In subgroup analyses, young athletes (<40 yr) presented increased baseline brachial artery diameter (mean difference, 0.40 mm; P < 0.00001) and similar FMD (SMD, 0.27; P = 0.22) compared with those in controls. In contrast, master athletes (>;50 yr) showed similar baseline brachial artery diameter (mean difference, 0.04 mm; P = 0.69) and increased FMD (SMD, 0.99; P = 0.0005) compared with those in controls. CONCLUSIONS The current meta-analysis provides evidence that master athletes but not young athletes exhibit greater FMD compared with that in age-matched healthy controls, thus suggesting that the association between high levels of exercise training and increased FMD is age dependent.

Endurance training and maximal oxygen consumption with ageing: Role of maximal cardiac output and oxygen extraction

Background The increase in maximal oxygen consumption (VO2max) with endurance training is associated with that of maximal cardiac output (Qmax), but not oxygen extraction, in young individuals. Whether such a relationship is altered with ageing remains unclear. Therefore, we sought systematically to review and determine the effect of endurance training on and the associations among VO2max, Qmax and arteriovenous oxygen difference at maximal exercise (Ca-vO2max) in healthy aged individuals. Design and methods We conducted a systematic search of MEDLINE, Scopus and Web of Science, from their inceptions until May 2015 for articles assessing the effect of endurance training lasting 3 weeks or longer on VO2max and Qmax and/or Ca-vO2max in healthy middle-aged and/or older individuals (mean age ≥40 years). Meta-analyses were performed to determine the standardised mean difference (SMD) in VO2max, Qmax and Ca-vO2max between post and pre-training measurements. Subgroup and meta-regression analyses were used to evaluate the associations among SMDs and potential moderating factors. Results Sixteen studies were included after systematic review, comprising a total of 153 primarily untrained healthy middle-aged and older subjects (mean age 42–71 years). Endurance training programmes ranged from 8 to 52 weeks of duration. After data pooling, VO2max (SMD 0.89; P < 0.0001) and Qmax (SMD 0.61; P < 0.0001) were increased after endurance training; no heterogeneity among studies was detected. Ca-vO2max was only increased with endurance training interventions lasting more than 12 weeks (SMD 0.62; P = 0.001). In meta-regression, the SMD in Qmax was positively associated with the SMD in VO2max (B = 0.79, P = 0.04). The SMD in Ca-vO2max was not associated with the SMD in VO2max (B = 0.09, P = 0.84). Conclusions The improvement in VO2max following endurance training is a linear function of Qmax, but not Ca-vO2max, through healthy ageing.

Repeated Sprint Training in Hypoxia Versus Normoxia Does Not Improve Performance: A Double-Blind and Cross-Over Study.

CONTEXT Few recent studies indicate that short-term repeated-sprint (RS) training in hypoxia (RSH) improves RS performance compared with identical training under normoxic conditions (RSN) in endurance-trained subjects. PURPOSE To determine the effects of RSH against RSN on RS performance under normoxic and moderate hypoxic conditions, using a randomized, doubleblind, crossover experimental design. METHODS Fifteen endurance-trained male subjects (age 25 ± 4 y) performed 4 wk of RS training (3 sessions/wk) in normobaric hypoxia (RSH, FiO2 = 13.8%) and normoxia (RSN, FiO2 = 20.9%) in a crossover manner. Before and after completion of training, RS tests were performed on a cycle ergometer with no prior exercise (RSNE), after an incremental exercise test (RSIE), and after a time-trial test (RSTT) in normoxia and hypoxia. RESULTS Peak power outputs at the incremental exercise test and time-trial performance were unaltered by RSH in normoxia and hypoxia. RS performance was generally enhanced by RSH, as well as RSN, but there were no additional effects of RSH over RSN on peak and mean sprint power output and the number of repeated sprints performed in the RSNE, RSIE, and RSTT trials under normoxic and hypoxic conditions. CONCLUSIONS The present double-blind crossover study indicates that RSH does not improve RS performance compared with RSN in normoxic and hypoxic conditions in endurance-trained subjects. Therefore, caution should be exercised when proposing RSH as an advantageous method to improve exercise performance.

Acute Hyperglycemia Impairs Vascular Function in Healthy and Cardiometabolic Diseased Subjects

Objectives—Controversy exists over the effect of acute hyperglycemia on vascular function. In this systematic review, we compared the effect of acute hyperglycemia on endothelial and vascular smooth muscle functions across healthy and cardiometabolic diseased subjects. Approach and Results—A systematic search of MEDLINE, EMBASE, and Web of Science from inception until July 2014 identified articles evaluating endothelial or vascular smooth muscle function during acute hyperglycemia and normoglycemia. Meta-analyses compared the standardized mean difference (SMD) in endothelial and vascular smooth muscle functions between acute hyperglycemia and normoglycemia. Subgroup analyses and metaregression identified sources of heterogeneity. Thirty-nine articles (525 healthy and 540 cardiometabolic subjects) were analyzed. Endothelial function was decreased (39 studies; n=1065; SMD, −1.25; 95% confidence interval, −1.52 to −0.98; P<0.01), whereas vascular smooth muscle function was preserved (6 studies; n=144; SMD, −0.07; 95% confidence interval, −0.30 to 0.16; P=0.55) during acute hyperglycemia compared with normoglycemia. Significant heterogeneity was detected among endothelial function studies (P<0.01). A subgroup analysis revealed that endothelial function was decreased in the macrocirculation (30 studies; n=884; SMD, −1.40; 95% confidence interval, −1.68 to −1.12; P<0.01) but not in the microcirculation (9 studies; n=181; SMD, −0.63; 95% confidence interval, −1.36 to 0.11; P=0.09). Similar results were observed according to health status. Macrovascular endothelial function was inversely associated with age, blood pressure, and low-density lipoprotein cholesterol and was positively associated with the postocclusion interval of vascular assessment. Conclusions—To our knowledge, this is the first systematic review and meta-analysis of its kind. In healthy and diseased subjects, we found evidence for macrovascular but not microvascular endothelial dysfunction during acute hyperglycemia.