Isometric Exercise Training and Arterial Hypertension: An Updated Review.

Hypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research.

Are There Interindividual Responses of Cardiovascular Disease Risk Markers to Acute Exercise? A Replicate Crossover Trial.

PURPOSE: Using a replicated crossover design, we quantified the response heterogeneity of postprandial cardiovascular disease risk marker responses to acute exercise. METHODS: Twenty men (mean (SD) age, 26 (6) yr; body mass index, 23.9 (2.4) kg·m -2 ) completed four 2-d conditions (two control, two exercise) in randomized orders. On days 1 and 2, participants rested and consumed two high-fat meals over 9 h. Participants ran for 60 min (61 (7)% of peak oxygen uptake) on day 1 (6.5 to 7.5 h) of both exercise conditions. Time-averaged total area under the curve (TAUC) for triacylglycerol, glucose, and insulin were calculated from 11 venous blood samples on day 2. Arterial stiffness and blood pressure responses were calculated from measurements at baseline on day 1 and at 2.5 h on day 2. Consistency of individual differences was explored by correlating the two replicates of control-adjusted exercise responses for each outcome. Within-participant covariate-adjusted linear mixed models quantified participant-by-condition interactions and individual response SDs. RESULTS: Acute exercise reduced mean TAUC-triacylglycerol (-0.27 mmol·L -1 ·h; Cohen's d = 0.29, P = 0.017) and TAUC-insulin (-25 pmol·L -1 ·h; Cohen's d = 0.35, P = 0.022) versus control, but led to negligible changes in TAUC-glucose and the vascular outcomes (Cohen's d ≤ 0.36, P ≥ 0.106). Small-to-moderate, but nonsignificant, correlations were observed between the two response replicates ( r = -0.42 to 0.15, P ≥ 0.066). We did not detect any individual response heterogeneity. All participant-by-condition interactions were P ≥ 0.137, and all individual response SDs were small with wide 95% confidence intervals overlapping zero. CONCLUSIONS: Large trial-to-trial within-subject variability inhibited detection of consistent interindividual variability in postprandial metabolic and vascular responses to acute exercise.

Analytical Performance of the Factory-Calibrated Flash Glucose Monitoring System FreeStyle Libre2TM in Healthy Women.

Continuous glucose monitoring (CGM) is used clinically and for research purposes to capture glycaemic profiles. The accuracy of CGM among healthy populations has not been widely assessed. This study assessed agreement between glucose concentrations obtained from venous plasma and from CGM (FreeStyle Libre2TM, Abbott Diabetes Care, Witney, UK) in healthy women. Glucose concentrations were assessed after fasting and every 15 min after a standardized breakfast over a 4-h lab period. Accuracy of CGM was determined by Bland-Altman plot, 15/15% sensor agreement analysis, Clarke error grid analysis (EGA) and mean absolute relative difference (MARD). In all, 429 valid CGM readings with paired venous plasma glucose (VPG) values were obtained from 29 healthy women. Mean CGM readings were 1.14 mmol/L (95% CI: 0.97 to 1.30 mmol/L, p < 0.001) higher than VPG concentrations. Ratio 95% limits of agreement were from 0.68 to 2.20, and a proportional bias (slope: 0.22) was reported. Additionally, 45% of the CGM readings were within ±0.83 mmol/L (±15 mg/dL) or ±15% of VPG, while 85.3% were within EGA Zones A + B (clinically acceptable). MARD was 27.5% (95% CI: 20.8, 34.2%), with higher MARD values in the hypoglycaemia range and when VPG concentrations were falling. The FreeStyle Libre2TM CGM system tends to overestimate glucose concentrations compared to venous plasma samples in healthy women, especially during hypoglycaemia and during glycaemic swings.

Associations of objectively measured physical activity, sedentary time and cardiorespiratory fitness with adipose tissue insulin resistance and ectopic fat.

BACKGROUND/OBJECTIVES: Inadequate movement, excess adiposity, and insulin resistance augment cardiometabolic risk. This study examined the associations of objectively measured moderate-to-vigorous intensity physical activity (MVPA), sedentary time and cardiorespiratory fitness (CRF), with adipose tissue insulin resistance and ectopic fat. METHODS: Data were combined from two previous experimental studies with community volunteers (n = 141, male = 60%, median (interquartile range) age = 37 (19) years, body mass index (BMI) = 26.1 (6.3) kg·m-2). Adipose tissue insulin resistance was assessed using the adipose tissue insulin resistance index (Adipo-IR); whilst magnetic resonance imaging (MRI) was used to measure liver, visceral (VAT) and subcutaneous abdominal adipose tissue (ScAT). Sedentary time and MVPA were measured via an ActiGraph GT3X+ accelerometer. Generalized linear models examined the association of CRF, MVPA, and sedentary time with Adipo-IR and fat depots. Interaction terms explored the moderating influence of age, sex, BMI and CRF. RESULTS: After controlling for BMI and cardiometabolic variables, sedentary time was positively associated with Adipo-IR (ß = 0.68 AU [95%CI = 0.27 to 1.10], P < 0.001). The association between sedentary time and Adipo-IR was moderated by age, CRF and BMI; such that it was stronger in individuals who were older, had lower CRF and had a higher BMI. Sedentary time was also positively associated with VAT (ß = 0.05 L [95%CI = 0.01 to 0.08], P = 0.005) with the relationship being stronger in females than males. CRF was inversely associated with VAT (ß = -0.02 L [95%CI = -0.04 to -0.01], P = 0.003) and ScAT (ß = -0.10 L [95%CI = -0.13 to -0.06], P < 0.001); with sex and BMI moderating the strength of associations with VAT and ScAT, respectively. CONCLUSIONS: Sedentary time is positively associated with adipose tissue insulin resistance which regulates lipogenesis and lipolysis. CRF is independently related to central fat storage which is a key risk factor for cardiometabolic disease.

Exploring the acute effects of running on cerebral blood flow and food cue reactivity in healthy young men using functional magnetic resonance imaging.

Acute exercise suppresses appetite and alters food-cue reactivity, but the extent exercise-induced changes in cerebral blood flow (CBF) influences the blood-oxygen-level-dependent (BOLD) signal during appetite-related paradigms is not known. This study examined the impact of acute running on visual food-cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2 ) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five-minute pseudo-continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD-fMRI was acquired during a food-cue reactivity task before and 28 min after exercise/rest. Food-cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trial p ≤ .018). No time-by-trial interactions for CBF were identified (p ≥ .087). Exercise induced moderate-to-large reductions in subjective appetite ratings (Cohen's d = 0.53-0.84; p ≤ .024) and increased food-cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise-induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food-cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF.

The influence of physical activity on neural responses to visual food cues in humans: A systematic review of functional magnetic resonance imaging studies.

This systematic review examined whether neural responses to visual food-cues measured by functional magnetic resonance imaging (fMRI) are influenced by physical activity. Seven databases were searched up to February 2023 for human studies evaluating visual food-cue reactivity using fMRI alongside an assessment of habitual physical activity or structured exercise exposure. Eight studies (1 exercise training, 4 acute crossover, 3 cross-sectional) were included in a qualitative synthesis. Structured acute and chronic exercise appear to lower food-cue reactivity in several brain regions, including the insula, hippocampus, orbitofrontal cortex (OFC), postcentral gyrus and putamen, particularly when viewing high-energy-density food cues. Exercise, at least acutely, may enhance appeal of low-energy-density food-cues. Cross-sectional studies show higher self-reported physical activity is associated with lower reactivity to food-cues particularly of high-energy-density in the insula, OFC, postcentral gyrus and precuneus. This review shows that physical activity may influence brain food-cue reactivity in motivational, emotional, and reward-related processing regions, possibly indicative of a hedonic appetite-suppressing effect. Conclusions should be drawn cautiously given considerable methodological variability exists across limited evidence.

Sedentary Time Is Independently Related to Adipose Tissue Insulin Resistance in Adults With or at Risk of Type 2 Diabetes.

INTRODUCTION: This cross-sectional study examined associations of device-measured sedentary time and moderate-to-vigorous physical activity (MVPA) with adipose tissue insulin resistance in people with or at high risk of type 2 diabetes (T2DM). METHOD: Data were combined from six previous experimental studies (within our group) involving patients with T2DM or primary risk factors (median (interquartile range) age, 66.2 (66.0-70.8) yr; body mass index (BMI), 31.1 (28.0-34.4) kg·m -2 ; 62% male; n = 179). Adipose tissue insulin resistance was calculated as the product of fasted circulating insulin and nonesterified fatty acids (ADIPO-IR), whereas sedentary time and MVPA were determined from wrist-worn accelerometery. Generalized linear models examined associations of sedentary time and MVPA with ADIPO-IR with interaction terms added to explore the moderating influence of ethnicity (White European vs South Asian), BMI, age, and sex. RESULTS: In finally adjusted models, sedentary time was positively associated with ADIPO-IR, with every 30 min of sedentary time associated with a 1.80-unit (95% confidence interval, 0.51-3.06; P = 0.006) higher ADIPO-IR. This relationship strengthened as BMI increased ( ß = 3.48 (95% confidence interval, 1.50-5.46), P = 0.005 in the upper BMI tertile (≥33.2 kg·m -2 )). MVPA was unrelated to ADIPO-IR. These results were consistent in sensitivity analyses that excluded participants taking statins and/or metformin ( n = 126) and when separated into the participants with T2DM ( n = 32) and those at high risk ( n = 147). CONCLUSIONS: Sedentary time is positively related to adipose tissue insulin sensitivity in people with or at high risk of T2DM. This relationship strengthens as BMI increases and may help explain established relationships between greater sedentary time, ectopic lipid, and hyperglycemia.

The impact of acute exercise on appetite control: Current insights and future perspectives.

The interaction of exercise with appetite control and energy intake has been widely studied due to the ability of exercise-related energy expenditure to influence energy and substrate balance. Many empirical studies have explored appetite and energy intake responses to acute (single) exercise bouts involving a variety of protocols in diverse populations revealing several consistent trends. The balance of evidence suggests that acute moderate-to-vigorous intensity land-based exercise suppresses subjective appetite feelings and the orexigenic hormone acylated ghrelin and elevates the anorexigenic hormones peptide YY and glucagon-like peptide-1. These perturbations are transient and hormone concentrations usually return to resting values in the hours after exercise without evoking compensatory increases in appetite or energy intake on the same day. This evidence counters the popular assertion that exercise transiently increases appetite and may prompt greater energy intake at subsequent meals. The indifference of the appetite control system to acute exercise-induced energy deficits contrasts with the immediate increases in appetite and energy intake provoked by equivalent diet-induced energy deficits. There is, however, considerable inter-individual variability in subjective appetite and hormonal responses to acute exercise with some individuals experiencing greater exercise-induced appetite suppression than others. Current evidence supports the promotion of exercise as a strategy for inducing a short-term energy deficit but the relevance of this for long-term appetite regulation and the control of body mass remains uncertain.

Circulating leukocyte cell-derived chemotaxin 2 and fibroblast growth factor 21 are negatively associated with cardiorespiratory fitness in healthy volunteers.

Leukocyte cell-derived chemotaxin-2 (LECT2) and fibroblast growth factor 21 (FGF21) are hepatokines that are regulated by energy balance and mediate insulin sensitivity and glycaemic control. This cross-sectional study examined the independent associations of cardiorespiratory fitness (CRF), moderate-to-vigorous intensity physical activity (MVPA), and sedentary time with circulating LECT2 and FGF21. Data were combined from two previous experimental studies in healthy volunteers (n = 141, male = 60%, mean ± SD age = 37 ± 19 years, body mass index (BMI) = 26.1 ± 6.3 kg·m-2). Sedentary time and MVPA were measured via an ActiGraph GT3X + accelerometer, while magnetic resonance imaging quantified liver fat. CRF was assessed using incremental treadmill tests. Generalized-linear models examined the association of CRF, sedentary time, and MVPA with LECT2 and FGF21 while controlling for key demographic and anthropometric variables. Interaction terms explored the moderating influence of age, sex, BMI, and CRF. In the fully adjusted models, each SD increase in CRF was independently associated with a 24% (95% CI: -37% to -9%, P = 0.003) lower plasma LECT2 concentration and 53% lower FGF21 concentration (95% CI: -73% to -22%, P = 0.004). Each SD increase in MVPA was independently associated with 55% higher FGF21 (95% CI: 12% to 114%, P = 0.006), and this relationship was stronger in those with lower BMI and higher levels of CRF. These findings demonstrate that CRF and wider activity behaviours may independently modulate the circulating concentrations of hepatokines and thereby influence inter-organ cross-talk.

How can physical activity facilitate a sustainable future? Reducing obesity and chronic disease.

This review examines the ways in which physical activity can contribute to a sustainable future by addressing significant public health issues. The review begins by identifying obesity and ageing as two major challenges facing societies around the world due to the association of both with the risk of chronic disease. Recent developments in the understanding and treatment of obesity are examined followed by an appraisal of the role of exercise alone and in combination with other therapies in preventing and managing obesity. The review then addresses the interaction between exercise and appetite due to the central role appetite plays in the development of overweight and obesity. The final section of the review examines the potential of physical activity to combat age-related chronic disease risk including CVD, cancer and dementia. It is concluded that while bariatric surgery and pharmacotherapy are the most effective treatments for severe obesity, physical activity has a role to play facilitating and enhancing weight loss in combination with other methods. Where weight/fat reduction via exercise is less than expected this is likely due to metabolic adaptation induced by physiological changes facilitating increased energy intake and decreased energy expenditure. Physical activity has many health benefits independent of weight control including reducing the risk of developing CVD, cancer and dementia and enhancing cognitive function in older adults. Physical activity may also provide resilience for future generations by protecting against the more severe effects of global pandemics and reducing greenhouse gas emissions via active commuting.

Effect of Acute Walking on Endothelial Function and Postprandial Lipemia in South Asians and White Europeans.

INTRODUCTION: South Asians (SAs) have an elevated risk of cardiovascular disease (CVD) compared with White Europeans (WEs). Postprandial endothelial function (flow-mediated dilatation (FMD%)) in SA women and SA men with central obesity has not been investigated. Research in other populations has highlighted that a 1% higher FMD% is associated with a ~13% lower risk of future CVD events. We investigated whether FMD% and lipemia, two markers for CVD risk, were higher in SAs versus WEs, whether walking improved FMD% and lipemia, and if there were ethnic differences in the response. METHODS: Lean premenopausal women (study 1; 12 SA, 12 WE) and men with central obesity (study 2; 15 SA, 15 WE) completed two 2-d trials. On day 1, participants walked for 60 min at 60% of their peak oxygen uptake or rested. On day 2, participants rested and consumed two high-fat meals over 8 h. Repeated ultrasound assessments of endothelial function and venous blood samples for CVD risk markers were taken. RESULTS: Compared with WEs, SAs had lower postprandial FMD% (study 1, -1.32%; study 2, -0.54%) and higher postprandial triacylglycerol concentrations (study 1, 0.31 mmol·L -1 ·h -1 ; study 2, 0.55 mmol·L -1 ·h -1 ). Walking improved postprandial FMD% (study 1, 1.12%; study 2, 0.94%) and resulted in no significant change or small reductions in postprandial triacylglycerol concentrations (study 1, -0.01 mmol·L -1 ·h -1 ; study 2, -0.25 mmol·L -1 ·h -1 ). Exercise-induced changes in FMD% and triacylglycerol were consistent between ethnic groups. CONCLUSIONS: Walking mitigated the adverse postprandial effect of a high-fat diet on FMD% to a similar extent in SA and WE women and men, even with no/small improvements in triacylglycerol. This study highlights the importance of exercise to clinically improve FMD% in SAs and WEs.

Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits.

Increasing evidence indicates that exercise has beneficial effects on chronic inflammation, cardiorespiratory function, muscle and bone strength and metabolic markers in adults with chronic kidney disease (CKD), kidney failure or kidney transplants. However, the mechanisms that underlie these benefits have received little attention, and the available clinical evidence is mainly from small, short-duration (<12 weeks) exercise intervention studies. The available data, mainly from patients with CKD or on dialysis, suggest that exercise-mediated shifts towards a less inflammatory immune cell profile, enhanced activity of the NRF2 pathway and reduced monocyte infiltration into adipose tissue may underlie improvements in inflammatory biomarkers. Exercise-mediated increases in nitric oxide release and bioavailability, reduced angiotensin II accumulation in the heart, left ventricular remodelling and reductions in myocardial fibrosis may contribute to improvements in left ventricular hypertrophy. Exercise stimulates an anabolic response in skeletal muscle in CKD, but increases in mitochondrial mass and satellite cell activation seem to be impaired in this population. Exercise-mediated activation of the canonical wnt pathway may lead to bone formation and improvements in the levels of the bone-derived hormones klotho and fibroblast growth factor 23 (FGF23). Longer duration studies with larger sample sizes are needed to confirm these mechanisms in CKD, kidney failure and kidney transplant populations and provide evidence for targeted exercise interventions.

The effect of acute and chronic exercise on hepatic lipid composition.

Exercise is recommended for those with, or at risk of nonalcoholic fatty liver disease (NAFLD), owing to beneficial effects on hepatic steatosis and cardiometabolic risk. Whilst exercise training reduces total intrahepatic lipid in people with NAFLD, accumulating evidence indicates that exercise may also modulate hepatic lipid composition. This metabolic influence is important as the profile of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) dramatically affect the metabolic consequences of hepatic lipid accumulation; with SFA being especially lipotoxic. Relatedly, obesity and NAFLD are associated with hepatic PUFA depletion and elevated SFA. This review summarizes the acute (single bout) and chronic (exercise training) effects of exercise on hepatic lipid composition in rodents (acute studies: n = 3, chronic studies: n = 13) and humans (acute studies: n = 1, chronic studies: n = 3). An increased proportion of hepatic PUFA after acute and chronic exercise is the most consistent finding of this review. Mechanistically, this may relate to an enhanced uptake of adipose-derived PUFA (reflecting habitual diet), particularly in rodents. A relative decrease in the proportion of hepatic MUFA after chronic exercise is also documented repeatedly, particularly in rodent models with elevated hepatic MUFA. This outcome is related to decreased hepatic stearoyl-CoA desaturase-1 activity in some studies. Findings regarding hepatic SFA are less consistent and limited by the absence of metabolic challenge in rodent models. These findings require confirmation in well-controlled interventions in people with NAFLD. These studies will be facilitated by recently validated magnetic resonance spectroscopy techniques, able to precisely quantify hepatic lipid composition in vivo.

Breaking up sitting with short frequent or long infrequent physical activity breaks does not lead to compensatory changes in appetite, appetite-regulating hormones or energy intake.

The aim of this study was to determine the appetite-related responses to breaking up prolonged sitting with physical activity bouts differing in frequency and duration among adult females. Fourteen sedentary females aged 34 ± 13 years with a body mass index of 27.1 ± 6.3 kg/m2 (mean ± SD) took part in a randomised crossover trial with three, 7.5 h conditions: (1) uninterrupted sitting (SIT), (2) sitting with short frequent 2-min moderate-intensity walking breaks every 30 min (SHORT-BREAKS), and (3) sitting with longer duration, less frequent 10-min moderate-intensity walking breaks every 170-180 min (LONG-BREAKS). The intensity and total duration of physical activity was matched between the SHORT-BREAKS and LONG-BREAKS conditions. Linear mixed models were used to compare the outcomes between conditions with significance being accepted as p ≤ 0.05. There were no significant between-condition differences in hunger, satisfaction, prospective food consumption or overall appetite area under the curve (AUC) (all p ≥ 0.801). Absolute ad libitum energy intake and relative energy intake (REI) did not differ significantly between conditions (all p ≥ 0.420). Acylated ghrelin and total peptide YY incremental and total AUC did not differ significantly between conditions (all p ≥ 0.388). Yet, there was a medium effect size for the higher acylated ghrelin incremental AUC in SHORT-BREAKS versus SIT (d = 0.61); the reverse was seen for total AUC, which was lower in SHORT-BREAKS versus SIT (d = 0.69). These findings suggest that breaking up sitting does not lead to compensatory changes in appetite, appetite hormones or energy intake regardless of physical activity bout duration and frequency among adult females.

Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: A systematic review and meta-analysis.

Single bouts of land-based exercise suppress appetite and do not typically alter energy intake in the short-term, whereas it has been suggested that water-based exercise may evoke orexigenic effects. The primary aim was to systematically review the available literature investigating the influence of water-based exercise on energy intake in adults (PROSPERO ID number CRD42022314349). PubMed, Medline, Sport-Discus, Academic Search Complete, CINAHL and Public Health Database were searched for peer-reviewed articles published in English from 1900 to May 2022. Included studies implemented a water-based exercise intervention versus a control or comparator. Risk of bias was assessed using the revised Cochrane 'Risk of bias tool for randomised trials' (RoB 2.0). We identified eight acute (same day) exercise studies which met the inclusion criteria. Meta-analysis was performed using a fixed effects generic inverse variance method on energy intake (8 studies (water versus control), 5 studies (water versus land) and 2 studies (water at two different temperatures)). Appetite and appetite-related hormones are also examined but high heterogeneity did not allow a meta-analysis of these outcome measures. We identified one chronic exercise training study which met the inclusion criteria with findings discussed narratively. Meta-analysis revealed that a single bout of exercise in water increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002). No difference in ad libitum energy intake was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Exercising in cold water (18-20 °C) increased energy intake to a greater extent than neutral water (27-33 °C) temperature (719 [222, 1215] kJ; P < 0.005). The one eligible 12-week study did not assess whether water-based exercise influenced energy intake but did find that cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively. To conclude, if body mass management is a person's primary focus, they should be mindful of the tendency to eat more in the hours after a water-based exercise session, particularly when the water temperature is cold (18-20 °C).

Physical activity is inversely associated with hepatic fibro-inflammation: A population-based cohort study using UK Biobank data.

Background & Aims: Physical activity (PA) is recommended in the management of non-alcoholic fatty liver disease (NAFLD) given its beneficial effects on liver fat and cardiometabolic risk. Using data from the UK Biobank population-cohort, this study examined associations between habitual PA and hepatic fibro-inflammation. Methods: A total of 840 men and women aged 55-70 years were included in this cross-sectional study. Hepatic fibro-inflammation (iron-corrected T1 [cT1]) and liver fat were measured using MRI, whilst body fat was measured using dual-energy X-ray absorptiometry. PA was measured using accelerometry. Generalised linear models examined associations between PA (light [LPA], moderate [MPA], vigorous [VPA], moderate-to-vigorous [MVPA] and mean acceleration) and hepatic cT1. Models were fitted for the whole sample and separately for upper and lower median groups for body and liver fat. Models were adjusted for sociodemographic and lifestyle variables. Results: In the full sample, LPA (-0.08 ms [-0.12 to -0.03]), MPA, (-0.13 ms [-0.21 to -0.05]), VPA (-1.16 ms [-1.81 to -0.51]), MVPA (-0.14 ms [-0.21 to -0.06]) and mean acceleration (-0.67 ms [-1.05 to-0.28]) were inversely associated with hepatic cT1. With the sample split by median liver or body fat, only VPA was inversely associated with hepatic cT1 in the upper median groups for body (-2.68 ms [-4.24 to -1.13]) and liver fat (-2.33 [-3.73 to -0.93]). PA was unrelated to hepatic cT1 in the lower median groups. Conclusions: Within a population-based cohort, device-measured PA is inversely associated with hepatic fibro-inflammation. This relationship is strongest with VPA and is greater in people with higher levels of body and liver fat. Lay summary: This study has shown that people who regularly perform greater amounts of physical activity have a reduced level of inflammation and fibrosis in their liver. This beneficial relationship is particularly strong when more intense physical activity is undertaken (i.e., vigorous-intensity), and is most visible in individuals with higher levels of liver fat and body fat.

Initiation of New Glucose-Lowering Therapies May Act to Reduce Physical Activity Levels: Pooled Analysis From Three Randomized Trials.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS: We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS: Liraglutide (mean -1,144 steps/day; 95% CI -2,069 to -220), empagliflozin (-1,132 steps/day; -1,739, -524), and sitagliptin (-852 steps/day; -1,625, -78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS: The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial.

AIM: To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. MATERIALS AND METHODS: In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/m2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24 weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. RESULTS: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions. CONCLUSIONS: In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy. CLINICAL TRIALS REGISTRATION: NCT02798744, www. CLINICALTRIALS: gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org.

The effect of exercise training on adipose tissue insulin sensitivity: A systematic review and meta-analysis.

This systematic review and meta-analysis determined the impact of exercise training on adipose tissue insulin sensitivity in adults. Its scope extended to studies measuring whole-body and localized subcutaneous adipose tissue insulin sensitivity using validated techniques. Consensus from four studies demonstrates that exercise training improved whole-body adipose tissue insulin sensitivity when measured via stable-isotope lipid tracers (rate of appearance suppression in response to hyperinsulinemia). Meta-analysis of 20 studies (26 intervention arms) employing the adipose tissue insulin resistance index (ADIPO-IR) supported these findings (-10.63 [-14.12 to -7.15] pmol·L-1 × mmol·L-1 ). With ADIPO-IR, this response was greater in studies documenting weight loss and shorter sampling time (≤48 h) post-training. Overall, exercise training did not affect whole-body adipose tissue insulin sensitivity in seven studies (11 intervention arms) measuring the suppression of circulating non-esterified fatty acids in response to insulin infusion (1.51 [-0.12 to 3.14]%); however, subgroup analysis identified an enhanced suppression post-training in trials reporting weight loss. From four microdialysis studies, consensus indicates no effect of exercise training on localized (abdominal/femoral) adipose tissue insulin sensitivity, potentially suggesting that enhanced whole-body responses are related to improvements in central adipose depots. However, heterogeneity within microdialysis protocols dictates that findings must be viewed with caution.