An Aerobic Cooldown After Morning, Fasted Resistance Exercise Has Limited Impact on Post-exercise Hyperglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Study.

OBJECTIVES: Expert guidelines recommend an aerobic cooldown to lower blood glucose for the management of post-exercise hyperglycemia. This strategy has never been empirically tested. Our aim in this study was to compare the glycemic effects of performing an aerobic cooldown vs not performing a cooldown after a fasted resistance exercise session. We hypothesized that the cooldown would lower blood glucose in the 30 minutes after exercise and would result in less time in hyperglycemia in the 6 hours after exercise. METHODS: Participants completed 2 identical resistance exercise sessions. One was followed by a low-intensity (30% of peak oxygen consumption) 10-minute cycle ergometer cooldown, and the other was followed by 10 minutes of sitting. We compared the changes in capillary glucose concentration during these sessions and continuous glucose monitoring (CGM) outcomes over 24 hours post-exercise. RESULTS: Sixteen participants completed the trial. Capillary glucose was similar between conditions at the start of exercise (p=0.07). Capillary glucose concentration decreased by 0.6±1.0 mmol/L during the 10-minute cooldown, but it increased by 0.7±1.3 mmol/L during the same time in the no-cooldown condition. The resulting difference in glucose trajectory led to a significant interaction (p=0.02), with no effect from treatment (p=0.7). Capillary glucose values at the end of recovery were similar between conditions (p>0.05). There were no significant differences in CGM outcomes. CONCLUSIONS: An aerobic cooldown reduces glucose concentration in the post-exercise period, but the small and brief nature of this reduction makes this strategy unlikely to be an effective treatment for hyperglycemia occurring after fasted exercise.

Effects of Exercise on Motivational Outcomes in Rectal Cancer Patients During and After Neoadjuvant Chemoradiation: A Phase II Randomized Controlled Trial.

OBJECTIVES: Understanding exercise motivation in rectal cancer patients during and after neoadjuvant chemoradiation therapy is important to improve adherence and achieve potential benefit. We report the motivational effects of exercise from the Exercise During and After Neoadjuvant Rectal Cancer Treatment trial. DATA SOURCES: We randomized 36 rectal cancer patients to supervised high-intensity interval training during neoadjuvant chemoradiation therapy followed by unsupervised moderate-to-vigorous exercise after therapy, or usual care. Using the theory of planned behavior, we assessed motivation, perceived benefits/harms, and perceived barriers for exercise during and after therapy. Supervised exercise during neoadjuvant chemoradiation therapy was experienced as meaningfully (d≥0.33) more controllable (p=0.08, d=0.60), more enjoyable (p=0.25, d=0.45), and less difficult (p=0.45, d=-0.38) than anticipated. Unsupervised exercise after therapy was experienced as meaningfully more enjoyable (p=0.047, d=0.50) and less difficult (p=0.43, d=-0.36), but also less controllable (p=0.14, d=-0.80) than anticipated. Common self-reported benefits of exercise both during and after neoadjuvant chemoradiation therapy were cardiovascular endurance, physical functioning, and quality of life. Common self-reported harms were exacerbation of treatment side effects. Frequently reported barriers to exercise during therapy were side effects of treatment, whereas exercise barriers after therapy were lack of motivation and lingering side effects. CONCLUSION: Exercise during and after therapy generally had positive effects on exercise motivation, however, perceived harms and barriers related to treatment side effects were identified. IMPLICATIONS FOR NURSING PRACTICE: Nurses can help rectal cancer patients initiate and maintain exercise during and after neoadjuvant chemoradiation by discussing the potential benefits, harms, and barriers to exercise.

Interaction of exercise and meal timing on blood glucose concentrations.

PURPOSE OF REVIEW: Exercise and diet are among the most studied behaviors that can affect blood glucose concentrations. Despite multiple studies examining these interventions in different populations and contexts, inconsistencies across studies have led to variable expectations. The purpose of this review is to more specifically examine how the timing of when exercise is performed in relation to meals can modify changes in glucose concentrations or insulin sensitivity. When possible, studies in type 2 diabetes are emphasized, but recent research in type 1 diabetes, obesity, and athletes is also considered. RECENT FINDINGS: The effect of a single bout of exercise performed after an overnight fast is often comparable to that of postprandial exercise on 24 h mean glucose concentrations. However, there is recent evidence to suggest that in some situations, but not all, longer term metabolic adaptations can be more favorable when exercise is regularly performed in the fasted state. SUMMARY: Exercise after an overnight fast can have different effects on glucose metabolism compared with postprandial exercise. The shorter term and longer term changes following fasting exercise can be relevant to those who are seeking greater glucoregulatory benefit from their exercise sessions, such as people with diabetes.

The Effect of Starting Blood Glucose Levels on Serum Electrolyte Concentrations during and after Exercise in Type 1 Diabetes.

Fear of hypoglycemia is a major exercise barrier for people with type 1 diabetes (PWT1D). Consequently, although guidelines recommend starting exercise with blood glucose (BG) concentration at 7-10 mmol/L, PWT1D often start higher, potentially affecting hydration and serum electrolyte concentrations. To test this, we examined serum and urine electrolyte concentrations during aerobic exercise (cycling 45 min at 60%VO2peak) in 12 PWT1D (10F/2M, mean ± SEM: age 29 ± 2.3 years, VO2peak 37.9 ± 2.2 mL·kg-1·min-1) with starting BG levels: 8-10 (MOD), and 12-14 (HI) mmol/L. Age, sex, and fitness-matched controls without diabetes (CON) completed one exercise session with BG in the normal physiological range. Serum glucose was significantly higher during exercise and recovery in HI versus MOD (p = 0.0002 and p < 0.0001, respectively) and in MOD versus CON (p < 0.0001). During exercise and recovery, MOD and HI were not significantly different in serum insulin (p = 0.59 and p = 0.63), sodium (p = 0.058 and p = 0.08), potassium (p = 0.17 and p = 0.16), calcium (p = 0.75 and 0.19), and magnesium p = 0.24 and p = 0.09). Our findings suggest that exercise of moderate intensity and duration with higher BG levels may not pose an immediate risk to hydration or serum electrolyte concentrations for PWT1D.

Implementation of weekday time-restricted eating to improve metabolic health in breast cancer survivors with overweight/obesity.

OBJECTIVE: This study aimed to evaluate the implementation of telephone-based delivery of weekday-only time-restricted eating (TRE), its preliminary efficacy for metabolic outcomes, and concurrent lifestyle changes. METHODS: Twenty-two breast cancer survivors aged 60+ years with overweight/obesity completed an 8-week feasibility study of 12 to 8 p.m. weekday-only ad libitum TRE. The intervention was delivered by one registered dietitian call, twice-daily automated text messages asking about eating start and stop times, and three support phone calls. Magnetic resonance imaging, venipuncture, and 3 days of diet records and accelerometry were performed at baseline and after intervention. RESULTS: Participants had a mean age of 66 (SD 5) years with BMI of 31.8 (4.8) kg/m2 . Intervention implementation was successful, including excellent adherence (98%), participant acceptability, and a low symptom profile and cost ($63/participant). There were no significant changes in individual components of metabolic syndrome, lipid profile, or hemoglobin A1c , despite clinically relevant changes occurring within individual participants. Magnetic resonance imaging-derived hepatic steatosis and thigh myosteatosis did not change. Dietary intake changes included reduced energy (-22%) and protein (-0.2 g/kg). Physical activity and sleep did not change. CONCLUSIONS: Eight weeks of telephone-delivered weekday TRE is a feasible, acceptable, low-symptom, and low-cost intervention. Future studies may consider a longer intervention length for more consistent metabolic improvements and counseling to enhance protein intake.

Systematic Review and Meta-analysis of Blood Glucose Response to High-intensity Interval Exercise in Adults With Type 1 Diabetes.

OBJECTIVES: Exercise-induced hyperglycemia is recognized in type 1 diabetes (T1D) clinical guidelines, but its association with high-intensity intermittent exercise (HIIE) in acute studies is inconsistent. In this meta-analysis, we examined the available evidence of blood glucose responses to HIIE in adults with T1D. The secondary, aim was to examine predictors of blood glucose responses to HIIE. We hypothesized that there would be no consistent effect on blood glucose from HIIE, unless examined in the context of participant prandial status. METHODS: We conducted a literature search using key words related to T1D and HIIE. Studies were required to include at least 6 participants with T1D with a mean age >18 years, involve an HIIE intervention, and contain pre- and postexercise measures of blood glucose. Analyses of extracted data were performed using a general inverse variance statistical method with a random effects model and a weighted multiple regression. RESULTS: Nineteen interventions from 15 reports were included in the analysis. A mean overall blood glucose decrease of -1.3 mmol/L (95% confidence interval [CI], -2.3 to -0.2 mmol/L) was found during exercise, albeit with high heterogeneity (I2=84%). When performed after an overnight fast, exercise increased blood glucose by +1.7 mmol/L (95% CI, 0.4 to 3.0 mmol/L), whereas postprandial exercise decreased blood glucose by -2.1 mmol/L (95% CI, -2.8 to -1.4 mmol/L), with a statistically significant difference between groups (p<0.0001). No associations with fitness (p=0.4), sex (p=0.4), age (p=0.9), exercise duration (p=0.9), or interval duration (p=0.2) were found. CONCLUSION: The effect of HIIE on blood glucose is inconsistent, but partially explained by prandial status.

Effects of exercise during and after neoadjuvant chemoradiation on symptom burden and quality of life in rectal cancer patients: a phase II randomized controlled trial.

PURPOSE: We previously demonstrated that exercise during and after neoadjuvant chemoradiation (NACRT) for rectal cancer may improve the rate of pathologic complete/near complete response. Here, we report the effects of exercise on symptom management and quality of life (QoL). METHODS: Rectal cancer patients (N = 36) were randomized to a supervised high-intensity interval training program during NACRT followed by unsupervised continuous exercise after NACRT or usual care. Patient-reported outcomes were assessed at baseline, post-NACRT, and presurgery including symptom burden (M.D. Anderson Symptom Inventory) and QoL (European Organisation for Research and Treatment of Cancer QLQ- C30 and -CR29). RESULTS: During NACRT, exercise significantly worsened stool frequency (adjusted between-group difference, 25.8; 95% CI, 4.0 to 47.6; p = 0.022), role functioning (adjusted between-group difference, -21.3; 95% CI, -41.5 to -1.1; p = 0.039), emotional functioning (adjusted between-group difference, -11.7; 95% CI, -22.0 to -1.4; p = 0.028), and cognitive functioning (adjusted between-group difference, -11.6; 95% CI, -19.2 to -4.0; p = 0.004) compared to usual care. After NACRT, exercise significantly worsened diarrhea (adjusted between-group difference, 1.2; 95% CI, 0.1 to 2.3; p = 0.030) and embarrassment (adjusted between-group difference, 19.7; 95% CI, 7.4 to 32.1; p = 0.003) compared to usual care. CONCLUSIONS: Exercise exacerbated some symptoms and worsened QoL during NACRT; however, most negative effects dissipated after NACRT. Larger trials are necessary to confirm these findings. IMPLICATIONS FOR CANCER SURVIVORS: If the clinical benefit of exercise is confirmed, then the modest symptom exacerbation during NACRT may be considered tolerable. However, in the absence of any clinical benefit, exercise may be contraindicated in this clinical setting.

Remission of type 2 diabetes and improved diastolic function by combining structured exercise with meal replacement and food reintroduction among young adults: the RESET for REMISSION randomised controlled trial protocol.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) onset before 40 years of age has a magnified lifetime risk of cardiovascular disease. Diastolic dysfunction is its earliest cardiac manifestation. Low energy diets incorporating meal replacement products can induce diabetes remission, but do not lead to improved diastolic function, unlike supervised exercise interventions. We are examining the impact of a combined low energy diet and supervised exercise intervention on T2DM remission, with peak early diastolic strain rate, a sensitive MRI-based measure, as a key secondary outcome. METHODS AND ANALYSIS: This prospective, randomised, two-arm, open-label, blinded-endpoint efficacy trial is being conducted in Montreal, Edmonton and Leicester. We are enrolling 100 persons 18-45 years of age within 6 years' T2DM diagnosis, not on insulin therapy, and with obesity. During the intensive phase (12 weeks), active intervention participants adopt an 800-900 kcal/day low energy diet combining meal replacement products with some food, and receive supervised exercise training (aerobic and resistance), three times weekly. The maintenance phase (12 weeks) focuses on sustaining any weight loss and exercise practices achieved during the intensive phase; products and exercise supervision are tapered but reinstituted, as applicable, with weight regain and/or exercise reduction. The control arm receives standard care. The primary outcome is T2DM remission, (haemoglobin A1c of less than 6.5% at 24 weeks, without use of glucose-lowering medications during maintenance). Analysis of remission will be by intention to treat with stratified Fisher's exact test statistics. ETHICS AND DISSEMINATION: The trial is approved in Leicester (East Midlands - Nottingham Research Ethics Committee (21/EM/0026)), Montreal (McGill University Health Centre Research Ethics Board (RESET for remission/2021-7148)) and Edmonton (University of Alberta Health Research Ethics Board (Pro00101088). Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial. TRIAL REGISTRATION NUMBER: ISRCTN15487120.

Effects of supervised high-intensity interval training on motivational outcomes in men with prostate cancer undergoing active surveillance: results from a randomized controlled trial.

BACKGROUND: Understanding the motivational effects of supervised aerobic high-intensity interval training (HIIT) may help men with prostate cancer undergoing active surveillance initiate and maintain exercise behavior, however, few studies have addressed this question. This report explored exercise motivation in men with prostate cancer undergoing active surveillance participating in a randomized exercise trial. METHODS: The Exercise during Active Surveillance for Prostate Cancer (ERASE) trial randomized 52 men with prostate cancer on active surveillance to the HIIT exercise group or the usual care (UC) group. The exercise program was supervised aerobic HIIT conducted three times per week for 12 weeks. The motivation questions were developed using the Theory of Planned Behavior and included motivational constructs, anticipated and experienced outcomes, and barriers to HIIT during active surveillance. RESULTS: The HIIT group attended 96% of the planned exercise sessions with 100% compliance to the exercise protocol. Motivation outcome data were obtained in 25/26 (96%) participants in the HIIT group and 25/26 (96%) participants in the UC group. At baseline, study participants were generally motivated to perform HIIT. After the intervention, the HIIT group reported that HIIT was even more enjoyable (p < 0.001; d = 1.38), more motivating (p = 0.001; d = 0.89), more controllable (p < 0.001; d = 0.85), and instilled more confidence (p = 0.004; d = 0.66) than they had anticipated. Moreover, compared to UC, HIIT participants reported significantly higher perceived control (p = 0.006; d = 0.68) and a more specific plan (p = 0.032; d = 0.67) for performing HIIT over the next 6 months. No significant differences were found in anticipated versus experienced outcomes. Exercise barriers were minimal, however, the most often reported barriers included pain or soreness (56%), traveling to the fitness center (40%), and being too busy and having limited time (36%). CONCLUSION: Men with prostate cancer on active surveillance were largely motivated and expected significant benefits from a supervised HIIT program. Moreover, the men assigned to the HIIT program experienced few barriers and achieved high adherence, which further improved their motivation. Future research is needed to understand long-term exercise motivation and behavior change in this setting. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03203460 . Registered on June 29, 2017.

A Randomized Trial of the Effects of Exercise on Anxiety, Fear of Cancer Progression and Quality of Life in Prostate Cancer Patients on Active Surveillance.

PURPOSE: We examined the effects of exercise on prostate cancer-specific anxiety, fear of cancer progression, quality of life and psychosocial outcomes in patients with prostate cancer on active surveillance. MATERIALS AND METHODS: The ERASE (Exercise during Active Surveillance for Prostate Cancer) Trial randomized 52 patients with prostate cancer undergoing active surveillance to high-intensity interval training (HIIT, 26 patients) or usual care (UC, 26 patients). The HIIT group performed a 12-week, thrice weekly, supervised, aerobic HIIT program. The UC group did not exercise. Patient-reported outcomes were assessed at baseline and after intervention, including prostate cancer-specific anxiety (Memorial Anxiety Scale for Prostate Cancer), fear of cancer progression (Fear of Cancer Recurrence Inventory), prostate cancer symptoms (Expanded Prostate Cancer Index Composite), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core) and psychological health outcomes (eg fatigue, stress and self-esteem). Analysis of covariance was used to compare between-group differences. RESULTS: Fifty of 52 participants (96%) completed patient-reported outcome assessments at 12 weeks. Adherence to HIIT was 96%. Compared to UC, HIIT significantly improved total prostate cancer-specific anxiety (adjusted between-group mean difference -2.7, 95% confidence interval, range -5.0 to -0.4, p=0.024), as well as the fear of progression subscale (p=0.013), hormonal symptoms (p=0.005), perceived stress (p=0.037), fatigue (p=0.029) and self-esteem (p=0.007). CONCLUSIONS: A 12-week supervised HIIT program may improve prostate cancer-specific anxiety, fear of cancer progression, hormone symptoms, stress, fatigue and self-esteem in men with prostate cancer on active surveillance. Larger trials are needed to confirm the effects of HIIT on patient-reported outcomes in the active surveillance setting.

A high-protein total diet replacement alters the regulation of food intake and energy homeostasis in healthy, normal-weight adults.

PURPOSE: Dietary intake can affect energy homeostasis and influence body weight control. The aim of this study was to compare the impact of high-protein total diet replacement (HP-TDR) versus a control (CON) diet in the regulation of food intake and energy homeostasis in healthy, normal-weight adults. METHODS: In this acute randomized controlled, cross-over study, participants completed two isocaloric arms: a) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat; b) CON: 55% carbohydrate, 15% protein, and 30% fat. The diets were provided for 32 h while inside a whole-body calorimetry unit. Appetite sensations, appetite-related hormones, and energy metabolism were assessed. RESULTS: Forty-three healthy, normal-weight adults (19 females) participated. Appetite sensations did not differ between diets (all p > 0.05). Compared to the CON diet, the change in fasting blood markers during the HP-TDR intervention was smaller for peptide tyrosine-tyrosine (PYY; - 18.9 ± 7.9 pg/mL, p = 0.02) and greater for leptin (1859 ± 652 pg/mL, p = 0.007). Moreover, postprandial levels of glucagon-like peptide 1 (1.62 ± 0.36 pM, p < 0.001) and PYY (31.37 ± 8.05 pg/mL, p < 0.001) were higher in the HP-TDR. Significant correlations were observed between energy balance and satiety (r = - 0.41, p = 0.007), and energy balance and PFC (r = 0.33, p = 0.033) in the HP-TDR. CONCLUSION: Compared to the CON diet, the HP-TDR increased blood levels of anorexigenic hormones. Moreover, females and males responded differently to the intervention in terms of appetite sensations and appetite-related hormones. TRIAL REGISTRATION: NCT02811276 (retrospectively registered on 16 June 2016) and NCT03565510 (retrospectively registered on 11 June 2018).

Associations between body mass index and bladder cancer survival: Is the obesity paradox short-lived?

INTRODUCTION: We investigated the associations of pre-surgical body mass index (BMI) with bladder cancer outcomes in patients treated with radical cystectomy. METHODS: We retrospectively analyzed data from 488 bladder cancer patients treated with radical cystectomy between 1994 and 2007 and followed up until 2016. Cox regression with step function (time-segment analysis) was conducted for overall survival because the proportional hazard assumption was violated. RESULTS: Of 488 bladder cancer patients, 155 (31.8%) were normal weight, 186 (38.1%) were overweight, and 147 (30.1%) were obese. During the median followup of 59.5 months, 363 (74.4%) patients died, including 197 (40.4%) from bladder cancer. In adjusted Cox regression analyses, BMI was not significantly associated with bladder cancer-specific survival for overweight (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.10, p=0.16) or obese (HR 0.76, 95% CI 0.52-1.09, p=0.13) patients. In the Cox regression with step function for overall survival, the time interaction was significant overall (p=0.020) and specifically for over-weight patients (p=0.006). In the time-segment model, the HR for overweight during the first 63 months was 0.66 (95% CI 0.49-0.90, p=0.008), whereas it was 1.41 (95% CI 0.89-2.23, p=0.14) after 63 months. Although not statistically significant, a similar pattern was observed for obese patients. CONCLUSIONS: Our findings suggest that overweight and obese bladder cancer patients had better outcomes within the first five years after radical cystectomy; however, there were no differences in longer-term survival. These data suggest that the obesity paradox in bladder cancer patients treated with radical cystectomy may be short-lived.

Bladder cancer and exeRcise trAining during intraVesical thErapy-the BRAVE trial: a study protocol for a prospective, single-centre, phase II randomised controlled trial.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of newly diagnosed bladder cancers. The treatment for NMIBC involves surgical removal of the tumour followed by 6 weekly instillations of immunotherapy or chemotherapy directly into the bladder (ie, intravesical therapy). NMIBC has a high rate of recurrence (31%-78%) and progression (15%). Moreover, bladder cancer and its treatment may affect patient functioning and quality of life. Exercise is a safe and effective intervention for many patient with cancer groups, however, no studies have examined exercise during intravesical therapy for NMIBC. The primary objective of the Bladder cancer and exeRcise trAining during intraVesical thErapy (BRAVE) trial is to examine the safety and feasibility of an exercise intervention in patients with bladder cancer undergoing intravesical therapy. The secondary objectives are to investigate the preliminary efficacy of exercise on health-related fitness and patient-reported outcomes; examine the social cognitive predictors of exercise adherence; and explore the potential effects of exercise on tumour recurrence and progression. METHODS AND ANALYSIS: BRAVE is a phase II randomised controlled trial that aims to include 66 patients with NMIBC scheduled to receive intravesical therapy. Participants will be randomly assigned to the exercise intervention or usual care. The intervention consists of three supervised, high-intensity interval training sessions per week for 12 weeks. Feasibility will be evaluated by eligibility, recruitment, adherence and attrition rates. Preliminary efficacy will focus on changes in cardiorespiratory fitness and patient-reported outcomes from baseline (prior to intravesical therapy) to pre-cystoscopy (3 months). Cancer outcomes will be tracked at 3 months, and 1-year follow-up by cystoscopy. Analysis of covariance will compare between-group differences at post-intervention (pre-cystoscopy) for all health-related fitness and patient-reported outcomes. ETHICS AND DISSEMINATION: The study was approved by the Health Research Ethics Board of Alberta-Cancer Committee (#20-0184). Dissemination will include publication and presentations at scientific conferences and public channels. TRIAL REGISTRATION NUMBER: NCT04593862; Pre-results.

Blood glucose concentration is unchanged during exposure to acute normobaric hypoxia in healthy humans.

Normal blood [glucose] regulation is critical to support metabolism, particularly in contexts of metabolic stressors (e.g., exercise, high altitude hypoxia). Data regarding blood [glucose] regulation in hypoxia are inconclusive. We aimed to characterize blood [glucose] over 80 min following glucose ingestion during both normoxia and acute normobaric hypoxia. In a randomized cross-over design, on two separate days, 28 healthy participants (16 females; 21.8 ± 1.6 years; BMI 22.8 ± 2.5 kg/m2 ) were randomly exposed to either NX (room air; fraction of inspired [FI ]O2 ~0.21) or HX (FI O2 ~0.148) in a normobaric hypoxia chamber. Measured FI O2 and peripheral oxygen saturation were both lower at baseline in hypoxia (p < 0.001), which was maintained over 80 min, confirming the hypoxic intervention. Following a 10-min baseline (BL) under both conditions, participants consumed a standardized glucose beverage (75 g, 296 ml) and blood [glucose] and physiological variables were measured at BL intermittently over 80 min. Blood [glucose] was measured from finger capillary samples via glucometer. Initial fasted blood [glucose] was not different between trials (NX:4.8 ± 0.4 vs. HX:4.9 ± 0.4 mmol/L; p = 0.47). Blood [glucose] was sampled every 10 min (absolute, delta, and percent change) following glucose ingestion over 80 min, and was not different between conditions (p > 0.77). In addition, mean, peak, and time-to-peak responses during the 80 min were not different between conditions (p > 0.14). There were also no sex differences in these blood [glucose] responses in hypoxia. We conclude that glucose regulation is unchanged in young, healthy participants with exposure to acute steady-state normobaric hypoxia, likely due to counterbalancing mechanisms underlying blood [glucose] regulation in hypoxia.

Effects of Exercise on Cardiorespiratory Fitness and Biochemical Progression in Men With Localized Prostate Cancer Under Active Surveillance: The ERASE Randomized Clinical Trial.

IMPORTANCE: Men with prostate cancer who are undergoing active surveillance are at an increased risk of cardiovascular death and disease progression. Exercise has been shown to improve cardiorespiratory fitness, physical functioning, body composition, fatigue, and quality of life during and after treatment; however, to date only 1 exercise study has been conducted in this clinical setting. OBJECTIVE: To examine the effects of exercise on cardiorespiratory fitness and biochemical progression in men with prostate cancer who were undergoing active surveillance. DESIGN, SETTING, AND PARTICIPANTS: The Exercise During Active Surveillance for Prostate Cancer (ERASE) trial was a single-center, 2-group, phase 2 randomized clinical trial conducted at the University of Alberta, Edmonton, Canada. Eligible patients were recruited from July 24, 2018, to February 5, 2020. Participants were adult men who were diagnosed with localized very low risk to favorable intermediate risk prostate cancer and undergoing active surveillance. They were randomized to either the high-intensity interval training (HIIT) group or usual care group. All statistical analyses were based on the intention-to-treat principle. INTERVENTIONS: The HIIT group was asked to complete 12 weeks of thrice-weekly, supervised aerobic sessions on a treadmill at 85% to 95% of peak oxygen consumption (V̇o2). The usual care group maintained their normal exercise levels. MAIN OUTCOMES AND MEASURES: The primary outcome was peak V̇o2, which was assessed as the highest value of oxygen uptake during a graded exercise test using a modified Bruce protocol. Secondary and exploratory outcomes were indicators of biochemical progression of prostate cancer, including prostate-specific antigen (PSA) level and PSA kinetics, and growth of prostate cancer cell line LNCaP. RESULTS: A total of 52 male patients, with a mean (SD) age of 63.4 (7.1) years, were randomized to either the HIIT (n = 26) or usual care (n = 26) groups. Overall, 46 of 52 participants (88%) completed the postintervention peak V̇o2 assessment, and 49 of 52 participants (94%) provided blood samples. Adherence to HIIT was 96%. The primary outcome of peak V̇o2 increased by 0.9 mL/kg/min in the HIIT group and decreased by 0.5 mL/kg/min in the usual care group (adjusted between-group mean difference (1.6 mL/kg/min; 95% CI, 0.3-2.9; P = .01). Compared with the usual care group, the HIIT group experienced decreased PSA level (-1.1 µg/L; 95% CI, -2.1 to 0.0; P = .04), PSA velocity (-1.3 µg /L/y; 95% CI, -2.5 to -0.1; P = .04), and LNCaP cell growth (-0.13 optical density unit; 95% CI, -0.25 to -0.02; P = .02). No statistically significant differences were found in PSA doubling time or testosterone. CONCLUSIONS AND RELEVANCE: The ERASE trial demonstrated that HIIT increased cardiorespiratory fitness levels and decreased PSA levels, PSA velocity, and prostate cancer cell growth in men with localized prostate cancer who were under active surveillance. Larger trials are warranted to determine whether such improvement translates to better longer-term clinical outcomes in this setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03203460.

Feasibility, Safety, and Preliminary Efficacy of Exercise During and After Neoadjuvant Rectal Cancer Treatment: A Phase II Randomized Controlled Trial.

BACKGROUND: Neoadjuvant chemoradiation (NACRT) improves outcomes for patients with rectal cancer; however, there are dose-limiting toxicities and only a 15% to 27% pathologic complete response (pCR) rate. Exercise may help manage toxicities and improve treatment response, but feasibility and early efficacy have not been established. EXERT was a phase II trial designed to establish the feasibility and safety of exercise and provide the first evidence of efficacy. MATERIALS AND METHODS: Patients with rectal cancer scheduled to receive NACRT were randomly assigned to usual care (n = 18) or exercise (n = 18) involving supervised exercise during NACRT and unsupervised exercise after NACRT. The primary outcome was cardiorespiratory fitness (VO2 peak). Clinical outcomes included treatment toxicities, treatment completion, and treatment response. RESULTS: Median attendance at supervised exercise sessions during NACRT was 82%, and median self-reported exercise after NACRT was 90 min/wk. From baseline to post-NACRT, VO2 peak increased by 0.4 mL·kg-1·min-1 in the exercise group and decreased by 0.8 mL·kg-1·min-1 in the usual care group (P = .47). There were no significant differences between groups for grade 3/4 toxicities or treatment completion. Of 18 patients in the exercise group, 10 (56%) achieved pCR/near pCR compared with 3 of 17 (18%) in the usual care group (P = .020). CONCLUSION: Exercise during and after NACRT is feasible for many patients with rectal cancer and may improve pCR despite limited fitness improvements. Larger trials are warranted to confirm if exercise is an effective intervention for improving treatment outcomes in this clinical setting.

Consumption of a High-Protein Meal Replacement Leads to Higher Fat Oxidation, Suppression of Hunger, and Improved Metabolic Profile After an Exercise Session.

The aim of this study was to compare the impact of a high-protein meal replacement (HP-MR) versus a control (CON) breakfast on exercise metabolism. In this acute, randomized controlled, cross-over study, participants were allocated into two isocaloric arms: (a) HP-MR: 30% carbohydrate, 43% protein, and 27% fat; (b) CON: 55% carbohydrate, 15% protein, and 30% fat. Following breakfast, participants performed a moderate-intensity aerobic exercise while inside a whole-body calorimetry unit. Energy expenditure, macronutrient oxidation, appetite sensations, and metabolic blood markers were assessed. Forty-three healthy, normal-weight adults (24 males) participated. Compared to the CON breakfast, the HP-MR produced higher fat oxidation (1.07 ± 0.33 g/session; p = 0.003) and lower carbohydrate oxidation (-2.32 ± 0.98 g/session; p = 0.023) and respiratory exchange ratio (-0.01 ± 0.00; p = 0.003) during exercise. After exercise, increases in hunger were lower during the HP-MR condition. Changes in blood markers from the fasting state to post-exercise during the HP-MR condition were greater for insulin, peptide tyrosine-tyrosine, and glucagon-like peptide 1, and lower for low-density lipoprotein cholesterol, triglyceride, and glycerol. Our primary findings were that an HP-MR produced higher fat oxidation during the exercise session, suppression of hunger, and improved metabolic profile after it.

A high-protein total diet replacement increases energy expenditure and leads to negative fat balance in healthy, normal-weight adults.

BACKGROUND: High-protein diets and total diet replacements are becoming increasingly popular for weight loss; however, further research is needed to elucidate their impact on the mechanisms involved in weight regulation. OBJECTIVE: The aim of this inpatient metabolic balance study was to compare the impact of a high-protein total diet replacement (HP-TDR) versus a control diet (CON) on select components of energy metabolism in healthy adults of both sexes. METHODS: The acute intervention was a randomized, controlled, crossover design with participants allocated to 2 isocaloric arms: 1) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat achieved through a nutritional supplement; 2) CON: 55% carbohydrate, 15% protein, and 30% fat. Participants received the prescribed diets for 32 h while inside a whole-body calorimetry unit (WBCU). The first dietary intervention randomly offered in the WBCU was designed to maintain energy balance and the second matched what was offered during the first stay. Energy expenditure, macronutrient oxidation rates and balances, and metabolic blood markers were assessed. Body composition was measured at baseline using DXA. RESULTS: Forty-three healthy, normal-weight adults (19 females and 24 males) were included. Compared with the CON diet, the HP-TDR produced higher total energy expenditure [(EE) 81 ± 82 kcal/d, P <0.001], protein and fat oxidation rates (38 ± 34 g/d, P <0.001; 8 ± 20 g/d, P = 0.013, respectively), and a lower carbohydrate oxidation rate (-38 ± 43 g/d, P <0.001). Moreover, a HP-TDR led to decreased energy (-112 ± 85 kcal/d; P <0.001), fat (-22 ± 20 g/d; P <0.001), and carbohydrate balances (-69 ± 44 g/d; P <0.001), and increased protein balance (90 ± 32 g/d; P <0.001). CONCLUSIONS: Our primary findings were that a HP-TDR led to higher total EE, increased fat oxidation, and negative fat balance. These results suggest that a HP-TDR may promote fat loss compared with a conventional isocaloric diet. These trials were registered at clinicaltrials.gov as NCT02811276 and NCT03565510.