Dose-response effects of exercise on insulin among colon cancer survivors.
ABSTRACT: Physical activity is associated with a lower risk of disease recurrence among colon cancer survivors. The pathways through which physical activity may alter disease outcomes are unknown, but may include changes in metabolic growth factors, such as insulin. Between January 2015 and August 2015, 39 stage I-III colon cancer survivors were randomized to one of the three groups: usual care control, 150?min/week of aerobic exercise (low-dose) and 300?min/week of aerobic exercise (high-dose) for six months. The pre-specified key metabolic growth factor outcome was fasting insulin. Insulin resistance was quantified using the homeostatic model assessment. Mean age was 56.5?±?10.0 years, 51% had stage III disease, 72% were treated with chemotherapy and the mean time since finishing treatment was 10.9?±?6.1 months. Over six months, the low-dose group completed 141.5?±?9.9?min/week of aerobic exercise, and the high-dose group completed 247.2?±?10.7?min/week of aerobic exercise. Fasting insulin concentrations decreased 7.4?±?9.4?pmol/L in the control group, 28.0?±?8.3?pmol/L in the low-dose group and 20.7?±?9.3?pmol/L in the high-dose group (nonlinear Ptrend?=?0.042). Insulin resistance decreased 0.11?±?0.20 in the control group, 0.63?±?0.17 in the low-dose group and 0.43?±?0.19 in the high-dose group (nonlinear Ptrend?=?0.012). Aerobic exercise reduces insulin concentrations and insulin resistance among patients with stage I-III colon cancer. Prescribing 150?min/week of aerobic exercise may be sufficient for reducing insulin concentrations and insulin resistance, which may partially mediate the relationship between physical activity and colon cancer prognosis.
Project description:BACKGROUND:Observational studies suggest that higher volumes of physical activity are associated with a lower risk of disease recurrence among survivors of colon cancer. However, the feasibility and safety of prescribing higher volumes of physical activity to survivors of colon cancer are unknown. Furthermore, the pathways through which exercise may reduce disease recurrence are unknown. PATIENTS AND METHODS:Survivors of stage I to III colon cancer were randomized to usual-care control, 150 minutes per week of aerobic exercise (low-dose), or 300 minutes per week of aerobic exercise (high-dose). Changes in soluble intercellular adhesion molecule-1 and vascular adhesion molecule-1 prognostic biomarkers were examined. RESULTS:From January 2015 to February 2016, 39 patients were enrolled (n = 13 usual-care control; n = 14 low-dose; n = 12 high-dose), and 38 participants completed the study (97% follow-up). Over 6 months, the low-dose group completed 142 minutes per week (92.8% adherence), and the high-dose group completed 247 minutes per week (89.0% adherence) of exercise. Compared with the control group, changes in soluble intercellular adhesion molecule-1 were -134.9 ng/mL (95% confidence interval, -238.1 to -31.6 ng/mL) in the low-dose group and -114.8 ng/mL (95% confidence interval, -222.5 to -7.1 ng/mL) in the high-dose group (linear Ptrend = .023; nonlinear Ptrend = .044). No changes were observed for soluable vascular adhesion molecule-1 (linear Ptrend = .791; nonlinear Ptrend = .604). Non-serious adverse events occurred at similar rates among randomized groups. No serious adverse events occurred. CONCLUSION:Higher volumes of moderate-intensity aerobic exercise, up to 300 minutes per week, are feasible, safe, and elicit favorable changes in prognostic biomarkers among patients recently treated for stage I to III colon cancer. These data can be used to guide clinical recommendations for patients, and inform future trials.
Project description:OBJECTIVE:To examine the dose-response effects of aerobic exercise on health-related quality of life (HRQoL) among colon cancer survivors. METHODS:Thirty-nine stage I to III colon cancer survivors were randomized to 1 of 3 groups: usual-care control, 150 min·wk-1 of aerobic exercise (low-dose) and 300 min·wk-1 of aerobic exercise (high-dose) for 6 months. HRQoL outcomes included the Short Form (SF)-36 physical and mental component summary, Functional Assessment of Cancer Therapy-Colorectal, Pittsburgh Sleep Quality Index, Fear of Cancer Recurrence Inventory, Fatigue Symptom Inventory, and North Central Cancer Treatment Group bowel function questionnaire, assessed at baseline and post intervention. The primary hypothesis was that exercise would improve HRQoL outcomes in a dose-response fashion, such that high-dose aerobic exercise would yield the largest improvements in HRQoL outcomes. RESULTS:Over 6 months, the low-dose group completed 141 ± 10 min·wk-1 of aerobic exercise, and the high-dose group completed 247 ± 11 min·wk-1 of aerobic exercise. Over 6 months, exercise improved the physical component summary score of the SF-36 (Ptrend = 0.002), the Functional Assessment of Cancer Therapy-Colorectal (Ptrend = 0.025), the Pittsburgh Sleep Quality Index (Ptrend = 0.049), and the Fatigue Symptom Inventory (Ptrend = 0.045) in a dose-response fashion. Between-group standardized mean difference effects sizes for the above-described findings were small to moderate in magnitude (0.35-0.75). No dose-response effects were observed for the mental component summary score of the SF-36, the Fear of Cancer Recurrence Inventory, or bowel function. CONCLUSION:Higher doses of aerobic exercise, up to 300 min·wk-1 , improve multiple HRQoL outcomes among stage I to III colon cancer survivors. These findings provide evidence that aerobic exercise may provide multiple health benefits for colon cancer survivors.
Project description:BACKGROUND:Physical activity is associated with a lower risk of disease recurrence among colon cancer survivors. Excess visceral adipose tissue is associated with a higher risk of disease recurrence among colon cancer survivors. The pathways through which physical activity may alter disease outcomes are unknown, but may be mediated by changes in visceral adipose tissue. METHODS:Thirty-nine stage I-III colon cancer survivors were randomised to one of three groups: usual-care control, 150?min?wk-1 of aerobic exercise (low dose) and 300?min?wk-1 of aerobic exercise (high dose) for 6 months. The prespecified key body composition outcome was visceral adipose tissue quantified using dual energy X-ray absorptiometry. RESULTS:Exercise reduced visceral adipose tissue in dose-response fashion (Ptrend=0.008). Compared with the control group, the low- and high-dose exercise groups lost 9.5?cm2 (95% CI: -22.4, 3.5) and 13.6?cm2 (95% CI: -27.0, -0.1) in visceral adipose tissue, respectively. Each 60?min?wk-1 increase in exercise predicted a 2.7?cm2 (95% CI: -5.4, -0.1) reduction in visceral adipose tissue. CONCLUSIONS:Aerobic exercise reduces visceral adipose tissue in dose-response fashion among patients with stage I-III colon cancer. Visceral adipose tissue may be a mechanism through which exercise reduces the risk of disease recurrence among colon cancer survivors.
Project description:<h4>Background</h4>Elevated glucose and insulin levels are major risk factors in the development of cardiometabolic disease. Aerobic exercise is widely recommended to improve glycaemic control, yet its acute effect on glycaemia and glucoregulatory hormones has not been systematically reviewed and analysed in healthy adults.<h4>Objective</h4>To determine the effect of a single bout of continuous aerobic exercise on circulating glucose, insulin, and glucagon concentrations in healthy adults.<h4>Methods</h4>CENTRAL, CINAHL, Embase, Global Health, HMIC, Medline, PubMed, PsycINFO, ScienceDirect, Scopus and Web of Science databases were searched from inception to May 2020. Papers were included if they reported a randomised, crossover study measuring glucose and/or insulin and/or glucagon concentrations before and immediately after a single bout of continuous aerobic exercise (≥ 30 min) compared to a time-matched, resting control arm in healthy adults. The risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Tool and GRADE approach, respectively. Random-effects meta-analyses were performed for glucose, insulin, and glucagon. Sub-group meta-analyses and meta-regression were performed for categorical (metabolic state [postprandial or fasted], exercise mode [cycle ergometer or treadmill]) and continuous (age, body mass index, % males, maximal aerobic capacity, exercise duration, exercise intensity) covariates, respectively.<h4>Results</h4>42 papers (51 studies) were considered eligible: glucose (45 studies, 391 participants), insulin (38 studies, 377 participants) and glucagon (5 studies, 47 participants). Acute aerobic exercise had no significant effect on glucose concentrations (mean difference: - 0.05 mmol/L; 95% CI, - 0.22 to 0.13 mmol/L; P = 0.589; I<sup>2</sup>: 91.08%, large heterogeneity; moderate-quality evidence). Acute aerobic exercise significantly decreased insulin concentrations (mean difference: - 18.07 pmol/L; 95% CI, - 30.47 to - 5.66 pmol/L; P = 0.004; I<sup>2</sup>: 95.39%, large heterogeneity; moderate-quality evidence) and significantly increased glucagon concentrations (mean difference: 24.60 ng/L; 95% CI, 16.25 to 32.95 ng/L; P < 0.001; I<sup>2</sup>: 79.36%, large heterogeneity; moderate-quality evidence). Sub-group meta-analyses identified that metabolic state modified glucose and insulin responses, in which aerobic exercise significantly decreased glucose (mean difference: - 0.27 mmol/L; 95% CI, - 0.55 to - 0.00 mmol/L; P = 0.049; I<sup>2</sup>: 89.72%, large heterogeneity) and insulin (mean difference: - 42.63 pmol/L; 95% CI, - 66.18 to - 19.09 pmol/L; P < 0.001; I<sup>2</sup>: 81.29%, large heterogeneity) concentrations in the postprandial but not fasted state. Meta-regression revealed that the glucose concentrations were also moderated by exercise duration and maximal aerobic capacity.<h4>Conclusions</h4>Acute aerobic exercise performed in the postprandial state decreases glucose and insulin concentrations in healthy adults. Acute aerobic exercise also increases glucagon concentrations irrespective of metabolic state. Therefore, aerobic exercise undertaken in the postprandial state is an effective strategy to improve acute glycaemic control in healthy adults, supporting the role of aerobic exercise in reducing cardiometabolic disease incidence.<h4>Prospero registration number</h4>CRD42020191345.
Project description:BACKGROUND:Physical activity is associated with a lower risk of disease recurrence among colon cancer patients. Circulating tumor cells (CTC) are prognostic of disease recurrence among stage I-III colon cancer patients. The pathways through which physical activity may alter disease outcomes are unknown, but may be mediated by changes in CTCs. METHODS:Participants included 23 stage I-III colon cancer patients randomized into one of three groups: usual-care control, 150 min?wk-1 of aerobic exercise (low-dose), and 300 min?wk-1 of aerobic exercise (high-dose) for six months. CTCs from venous blood were quantified in a blinded fashion using an established microfluidic antibody-mediated capture device. Poisson regression models estimated the logarithmic counts of CTCs. RESULTS:At baseline, 78% (18/23) of patients had ?1 CTC. At baseline, older age (-0.12±0.06; P = 0.04), lymphovascular invasion (0.63±0.25; P = 0.012), moderate/poor histology (1.09±0.34; P = 0.001), body mass index (0.07±0.02; P = 0.001), visceral adipose tissue (0.08±0.04; P = 0.036), insulin (0.06±0.02; P = 0.011), sICAM-1 (0.04±0.02; P = 0.037), and sVCAM-1 (0.06±0.03; P = 0.045) were associated with CTCs. Over six months, significant decreases in CTCs were observed in the low-dose (-1.34±0.34; P<0.001) and high-dose (-1.18±0.40; P = 0.004) exercise groups, whereas no significant change was observed in the control group (-0.59±0.56; P = 0.292). Over six months, reductions in body mass index (-0.07±0.02; P = 0.007), insulin (-0.08±0.03; P = 0.014), and sICAM-1 (-0.07±0.03; P = 0.005) were associated with reductions in CTCs. The main limitations of this proof-of-concept study are the small sample size, heterogenous population, and per-protocol statistical analysis. CONCLUSION:Exercise may reduce CTCs among stage I-III colon cancer patients. Changes in host factors correlated with changes in CTCs. Exercise may have a direct effect on CTCs and indirect effects through alterations in host factors. This hypothesis-generating observation derived from a small pilot study warrants further investigation and replication.
Project description:OBJECTIVE:To examine whether a combined aerobic exercise and resistance exercise is more effective than either aerobic exercise or resistance exercise alone in improving insulin sensitivity and reducing total adiposity and ectopic fat in adolescents. STUDY DESIGN:A total of 118 sedentary adolescents with overweight/obesity (body mass index >85th percentile, 12-17 years) were recruited from October 2013 through April 2017 at Children's Hospital of Pittsburgh. Participants were randomized to 1 of the following 6-month exercise groups (3 d/wk, 180?min/wk): aerobic exercise (n?=?38), resistance exercise (n?=?40), and combined aerobic exercise and resistance exercise (n?=?40). The primary outcome was the change in insulin-stimulated glucose disposal by a 3-hour hyperinsulinemic-euglycemic clamp. The secondary outcomes were changes in liver fat by proton magnetic resonance spectroscopy and intermuscular adipose tissue by computed tomography. RESULTS:Of the 118 participants randomized, 85 participants (72%) completed the study with 90% exercise attendance. Total adiposity reduced similarly in all groups (-2%, P?<?.05). After adjusting for age and sex, insulin-stimulated glucose disposal increased (P?<?.05) in all groups, with the increase in the aerobic exercise group being greater than the resistance exercise group (1.7?±?0.1 vs 0.7?±?0.1?mg/kg/min, P?<?.05) but not different from the combined group (1.2?±?0.1?mg/kg/min). Liver fat was reduced (P?<?.05) in the aerobic exercise (-0.6%) and combined (-0.6%) groups but not in the resistance exercise group (-0.3%, P?>?.05). Intermuscular adipose tissue decreased (P?<?.05) similarly in all groups. CONCLUSION:Combined aerobic exercise and resistance exercise and aerobic exercise alone are similarly beneficial in improving insulin sensitivity and reducing ectopic fat in adolescents with obesity. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01938950.
Project description:The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses.Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables.Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions.Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.
Project description:PURPOSE:This study assessed how individuals compensate for energy expended during a 12-wk aerobic exercise intervention, elucidating potential mechanisms and the role exercise dose plays in the compensatory response. PARTICIPANTS AND DESIGN:Three-arm, randomized controlled trial among sedentary adults age 18 to 40 yr, body mass index of 25 to 35. Groups included six exercise sessions per week, two sessions per week, and sedentary control. METHODS:Rate of exercise energy expenditure was calculated from a graded exercise test averaged across five heart rate zones. Energy compensation was calculated as the difference between expected weight loss (based on exercise energy expenditure) and changes in fat and fat-free mass (DXA). Resting energy expenditure was assessed via indirect calorimetry and concentrations of acylated ghrelin, leptin, insulin, and Glucagon-like peptide 1 (GLP-1) were assessed fasting and postprandial (six timepoints over 2 h). RESULTS:The 6-d·wk group expended more energy (2753.5 kcal) and exercised longer (320.5 min) per week than the 2-d·wk group (1490.7 kcal, 1888.8 min, P < 0.05), resulting in greater fat loss compared with the 2-d or control groups (P < 0.05). Exercise groups did not differ in the % or total kcal compensated. Greater decreases in area under the curve (AUC) for acylated ghrelin predicted greater fat loss, regardless of group, energy expended per week, exercise duration, or exercise intensity. Changes in leptin AUC was the only independent predictor for energy compensation, with a greater decrease in leptin AUC predicting less energy compensation. Exercise frequency, energy expended, duration, or intensity did not influence energy compensation. CONCLUSIONS:Leptin is an important factor in successful weight loss through exercise, with greater postprandial decreases promoting less compensation. Greater amounts of exercise do not influence the compensatory response to an exercise-induced energy deficit.
Project description:Previous studies have demonstrated that an acute bout of aerobic exercise induces a subsequent delayed onset of hypoglycemia among patients with type 1 diabetes. However, the mechanisms of exercise-induced hypoglycemia in type 1 diabetes are still unclear. Streptozotocin (STZ) was injected to 6-week-old male Wistar rats, and three days after STZ injection, animals were randomly assigned into 2 groups: STZ with insulin only (STZ) and STZ with insulin and exercise (STZ+EX). Normal Wistar rats with exercise were used as control (CON+EX). Insulin was intraperitoneally injected (0.5 U/kg) to both STZ groups (-0.5 h), and a bout of aerobic exercise (15 m/min for 30 min) was conducted at euglycemic conditions (0 h). Blood was collected at 0, 1, 3, and 5 h after exercise from the carotid artery. While the blood glucose level was stable during the post-exercise period (0-5 h) in the STZ and CON+EX groups, it decreased significantly only in the STZ+EX group at 3 h. Plasma glucagon, adrenalin, and noradrenalin levels significantly increased at 1 h in the STZ group, whereas significant hormonal responses were observed at 5 h in the STZ+EX group. In skeletal muscle glucose metabolism-related pathway, the level of glucose transporter-4 (GLUT-4) translocation was significantly higher at 1 h in the CON and STZ groups. However, in the STZ+EX group, these activations were maintained by 5 h, indicating a sustained glucose metabolism in the STZ+EX group. A single bout of aerobic exercise induced a delayed onset of hypoglycemia in STZ-treated rats. A prolonged enhancement of GLUT-4 translocation and delayed counter-regulatory hormone responses may have contributed to the induction of hypoglycemia.
Project description:The mechanisms whereby regular exercise reduces chronic inflammation remain unclear. We investigated whether regular aerobic exercise alters basal levels of interleukin (IL)-10 and IL-4 in two randomized trials of physical activity. The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA, n = 320) and the Breast Cancer and Exercise Trial in Alberta (BETA, n = 400) were two-center, two-armed randomized trials in inactive, healthy, postmenopausal women. Both trials included an exercise intervention prescribed five times/week and no dietary changes. In ALPHA, the exercise group was prescribed 225 min/week versus no activity in the controls. BETA examined dose-response effects comparing 300 (HIGH) versus 150 (MODERATE) min/week. Plasma concentrations of IL-10 and IL-4 were measured at baseline, 6, and 12 months. Intention-to-treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. Circulating anti-inflammatory cytokine levels decreased among all groups, with percent change ranging from -3.4% (controls) to -8.2% (HIGH) for IL-4 and -1.6% (controls) to -7.5% (HIGH) for IL-10. No significant group differences were found for IL-4 (ALPHA P = 0.54; BETA P = 0.32) or IL-10 (ALPHA P = 0.84; BETA P = 0.68). Some evidence for moderation of the effect of exercise by baseline characteristics was found for IL-10 but not for IL-4. Results from these two large randomized aerobic exercise intervention trials suggest that aerobic exercise does not alter IL-10 or IL-4 in a manner consistent with chronic disease and cancer prevention.