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Effect of diet with or without exercise on abdominal fat in postmenopausal women - a randomised trial.
van Gemert, WA, Peeters, PH, May, AM, Doornbos, AJH, Elias, SG, van der Palen, J, Veldhuis, W, Stapper, M, Schuit, JA, Monninkhof, EM
BMC public health. 2019;(1):174
Abstract
BACKGROUND We assessed the effect of equivalent weight loss with or without exercise on (intra-) abdominal fat in postmenopausal women in the SHAPE-2 study. METHODS The SHAPE-2 study is a three-armed randomised controlled trial conducted in 2012-2013 in the Netherlands. Postmenopausal overweight women were randomized to a diet (n = 97), exercise plus diet (n = 98) or control group (n = 48). Both intervention groups aimed for equivalent weight loss (6-7%) following a calorie-restricted diet (diet group) or a partly supervised intensive exercise programme (4 h per week) combined with a small caloric restriction (exercise plus diet group). Outcomes after 16 weeks are amount and distribution of abdominal fat, measured by magnetic resonance imaging (MRI) with the use of the three-point IDEAL Dixon method. RESULTS The diet and exercise plus diet group lost 6.1 and 6.9% body weight, respectively. Compared to controls, subcutaneous and intra-abdominal fat reduced significantly with both diet (- 12.5% and - 12.0%) and exercise plus diet (- 16.0% and - 14.6%). Direct comparison between both interventions revealed that the reduction in subcutaneous fat was statistically significantly larger in the group that combined exercise with diet: an additional 10.6 cm2 (95%CI -18.7; - 2.4) was lost compared to the diet-only group. Intra-abdominal fat loss was not significantly larger in the exercise plus diet group (- 3.8 cm2, 95%CI -9.0; 1.3). CONCLUSIONS We conclude that weight loss of 6-7% with diet or with exercise plus diet reduced both subcutaneous and intra-abdominal fat. Only subcutaneous fat statistically significantly reduced to a larger extent when exercise is combined with a small caloric restriction. TRIAL REGISTER NCT01511276 (clinicaltrials.gov), prospectively registered.
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Cost-effectiveness analysis of an 18-week exercise programme for patients with breast and colon cancer undergoing adjuvant chemotherapy: the randomised PACT study.
May, AM, Bosch, MJ, Velthuis, MJ, van der Wall, E, Steins Bisschop, CN, Los, M, Erdkamp, F, Bloemendal, HJ, de Roos, MA, Verhaar, M, et al
BMJ open. 2017;(3):e012187
Abstract
OBJECTIVE Meta-analyses show that exercise interventions during cancer treatment reduce cancer-related fatigue. However, little is known about the cost-effectiveness of such interventions. Here we aim to assess the cost-effectiveness of the 18-week physical activity during cancer treatment (PACT) intervention for patients with breast and colon cancer. The PACT trial showed beneficial effects for fatigue and physical fitness. DESIGN Cost-effectiveness analyses with a 9-month time horizon (18 weeks of intervention and 18 weeks of follow-up) within the randomised controlled multicentre PACT study. SETTING Outpatient clinics of 7 hospitals in the Netherlands (1 academic and 6 general hospitals) PARTICIPANTS 204 patients with breast cancer and 33 with colon cancer undergoing adjuvant treatment including chemotherapy. INTERVENTION Supervised 1-hour aerobic and resistance exercise (twice per week for 18 weeks) or usual care. MAIN OUTCOME MEASURES Costs, quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio. RESULTS For colon cancer, the cost-effectiveness analysis showed beneficial effects of the exercise intervention with incremental costs savings of €4321 and QALY improvements of 0.03. 100% of bootstrap simulations indicated that the intervention is dominant (ie, cheaper and more effective). For breast cancer, the results did not indicate that the exercise intervention was cost-effective. Incremental costs were €2912, and the incremental effect was 0.01 QALY. At a Dutch threshold value of €20 000 per QALY, the probability that the intervention is cost-effective was 2%. CONCLUSIONS Our results suggest that the 18-week exercise programme was cost-effective for colon cancer, but not for breast cancer. TRIAL REGISTRATION NUMBER ISRCTN43801571.
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Association between changes in fat distribution and biomarkers for breast cancer.
van Gemert, WA, Monninkhof, EM, May, AM, Elias, SG, van der Palen, J, Veldhuis, W, Stapper, M, Stellato, RK, Schuit, JA, Peeters, PH
Endocrine-related cancer. 2017;(6):297-305
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Abstract
We assessed the associations between changes in total and abdominal fat and changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In the SHAPE-2 trial, 243 postmenopausal overweight women were included. The intervention in this trial consisted of 5-6 kg weight loss either by diet only or exercise plus diet. After 16 weeks, we measured serum sex hormones, inflammatory markers, total body fat (measured by DEXA scan) and intra and subcutaneous abdominal fat (measured by MRI). Associations between changes in different body fat depots and biomarkers were analysed by linear regression using the study cohort irrespective of randomisation to make maximal use of the distribution of changes in fat measures. We found that a loss in total body fat was associated with favourable changes in free oestradiol, free testosterone, leptin and sex hormone binding globulin (SHBG). The loss of intra-abdominal fat was associated with a decrease in free testosterone, hsCRP and leptin, and an increase in SHBG. In the multivariable analysis, the best fitted models for the biomarkers free oestradiol, SHBG leptin and adiponectin included only total body fat. For free testosterone, this was subcutaneous abdominal fat, and for hsCRP and IL-6, only intra-abdominal fat change was important. For IL-6 and adiponectin, however, associations were weak and not significant. We conclude that, in our population of healthy overweight postmenopausal women, loss of fat at different body locations was associated with changes in different types of biomarkers, known to be related to risk of breast cancer.
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Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy.
Van Vulpen, JK, Velthuis, MJ, Steins Bisschop, CN, Travier, N, Van Den Buijs, BJ, Backx, FJ, Los, M, Erdkamp, FL, Bloemendal, HJ, Koopman, M, et al
Medicine and science in sports and exercise. 2016;(5):767-75
Abstract
PURPOSE Fatigue is a common problem among colon cancer patients and typically increases during chemotherapy. Exercise during chemotherapy might have beneficial effects on fatigue. To investigate the short- and long-term effects of an exercise program in colon cancer patients during adjuvant treatment, the Physical Activity During Cancer Treatment study was conducted. METHODS In this multicenter randomized controlled trial, 33 colon cancer patients undergoing chemotherapy (21 men and 12 women) were randomly assigned to either a group receiving an 18-wk supervised exercise program (n = 17) or to usual care (n = 16). The primary outcome was fatigue as measured by the Multidimensional Fatigue Inventory and the Fatigue Quality List. Secondary outcomes were quality of life, physical fitness, anxiety, depression, body weight, and chemotherapy completion rate. Outcome assessment took place at baseline, postintervention (18 wk) and at 36 wk. RESULTS Intention-to-treat mixed linear model analyses showed that patients in the intervention group experienced significantly less physical fatigue at 18 wk and general fatigue at 36 wk (mean between group differences, -3.2; 95% confidence interval [CI], -6.2 to -0.2; effect size [ES], -0.9 and -2.7; 95% CI, -5.2 to -0.1; ES, -0.8, respectively), and reported higher physical functioning (12.3; 95% CI, 3.3-21.4; ES, 1.0) compared with patients in the usual care group. CONCLUSION The Physical Activity During Cancer Treatment trial shows that an 18-wk supervised exercise program in colon cancer patients during chemotherapy is safe and feasible. The intervention significantly reduced physical fatigue at 18 wk and general fatigue at 36 wk. Considering the number of patients included in the present study, replication in a larger study population is required.
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Effect of Weight Loss with or without Exercise on Inflammatory Markers and Adipokines in Postmenopausal Women: The SHAPE-2 Trial, A Randomized Controlled Trial.
van Gemert, WA, May, AM, Schuit, AJ, Oosterhof, BY, Peeters, PH, Monninkhof, EM
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2016;(5):799-806
Abstract
BACKGROUND We investigated the effect of equivalent weight loss, by a hypocaloric diet or mainly exercise, on inflammatory markers and adipokines in overweight postmenopausal women. METHODS Women were randomized to a diet (n = 97), mainly exercise (n = 98), or control group (n = 48). Goal of both interventions was to lose 5 to 6 kg bodyweight by a hypocaloric diet or an exercise program (4 hours/week) combined with a small caloric intake restriction. Outcomes after 16 weeks included serum high-sensitive C-reactive protein (hsCRP), IL6, adiponectin, and leptin. RESULTS Both intervention groups achieved the target weight loss. Controls remained weight stable. Compared with control, hsCRP decreased with mainly exercise [treatment effect ratio (TER) = 0.64] and borderline statistically significant with diet (TER = 0.77). There was a suggestively larger effect of exercise, directly compared with diet (TER = 0.83). Leptin decreased with both interventions: mainly exercise (TER = 0.55) and diet (TER = 0.59), versus control. Effects attenuated and lost significance after adjusting for change in body fat percentage, and to a lesser extent when adjusting for fitness. No effects were seen on IL6 and adiponectin. CONCLUSIONS A 16-week randomized intervention inducing comparable weight loss by a hypocaloric diet or mainly exercise, resulted in favorable effects on serum hsCRP and leptin. We found a possible more beneficial effect on hsCRP with mainly exercise versus diet. These effects of exercise were established by changes in body fat percentage and physical fitness. IMPACT A modest amount of weight loss in postmenopausal women reduces hsCRP and leptin levels which might be associated with a lower breast cancer risk. Cancer Epidemiol Biomarkers Prev; 25(5); 799-806. ©2016 AACR.
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Effect of exercise on insulin sensitivity in healthy postmenopausal women: the SHAPE study.
van Gemert, WA, Monninkhof, EM, May, AM, Peeters, PH, Schuit, AJ
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015;(1):81-7
Abstract
BACKGROUND An inactive lifestyle is a risk factor for several types of cancer. A proposed pathway through which exercise influences cancer risk is via insulin. We aim to investigate the effect of a one-year exercise intervention on insulin sensitivity, and the role of body fat in this association, in healthy, normal to overweight/obese, postmenopausal women. METHODS In the Sex Hormones And Physical Exercise (SHAPE) study, 189 healthy, inactive and postmenopausal women [ages, 50-69 years; body mass index (BMI), 22-40 kg/m(2)] were randomly assigned to a one-year aerobic and strength exercise intervention (150 min/wk), or a control group. Between-group differences in fasting insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA2) over time were estimated using linear mixed models. RESULTS Follow-up measurements of insulin sensitivity were available for 181 (95.8%) and 182 (96.3%) women at 4 and 12 months, respectively. The intention-to-treat analysis showed no significant differences between the two study groups [treatment effect ratio of the exercise group vs. control (β; 95% confidence interval): insulin, β, 1.07 (0.96-1.19); glucose, β, 1.01 (0.99-1.02); and HOMA2, β, 1.07 (0.96-1.20)]. Similar results were found in a per protocol analysis in compliant women, and in a subgroup of women who lost >2% body fat [measured by dual-energy X-ray absorptiometry (DEXA)]. CONCLUSIONS Participation in a one-year aerobic and strength exercise intervention program did not result in changes in insulin sensitivity in healthy postmenopausal and inactive women. IMPACT Our findings suggest that 150 min/wk of exercise, as recommended by current guidelines, is not enough to achieve improvements in insulin sensitivity and subsequent cancer risk, in healthy postmenopausal women.
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Quality of Life after Diet or Exercise-Induced Weight Loss in Overweight to Obese Postmenopausal Women: The SHAPE-2 Randomised Controlled Trial.
van Gemert, WA, van der Palen, J, Monninkhof, EM, Rozeboom, A, Peters, R, Wittink, H, Schuit, AJ, Peeters, PH
PloS one. 2015;(6):e0127520
Abstract
INTRODUCTION This study investigates the effect of a modest weight loss either by a calorie restricted diet or mainly by increased physical exercise on health related quality of life (HRQoL) in overweight-to-obese and inactive postmenopausal women. We hypothesize that HRQoL improves with weight loss, and that exercise-induced weight loss is more effective for this than diet-induced weight loss. METHODS The SHAPE-2 trial was primarily designed to evaluate any additional effect of weight loss by exercise compared with a comparable amount of weight loss by diet on biomarkers relevant for breast cancer risk. In the present analysis we focus on HRQoL. We randomly assigned 243 eligible women to a diet (n = 97), exercise (n = 98), or control group (n = 48). Both interventions aimed for 5-6 kg weight loss. HRQoL was measured at baseline and after 16 weeks by the SF-36 questionnaire. RESULTS Data of 214 women were available for analysis. Weight loss was 4.9 kg (6.1%) and 5.5 kg (6.9%) with diet and exercise, respectively. Scores of the SF-36 domain 'health change' increased significantly by 8.8 points (95% CI 1.6;16.1) with diet, and by 20.5 points (95% CI 13.2;27.7) with exercise when compared with control. Direct comparison of diet and exercise showed a statistically significantly stronger improvement with exercise. Both intervention groups showed a tendency towards improvements in most other domains, which were more pronounced in the exercise group, but not statistically different from control or each other. CONCLUSION In a randomized trial in overweight-to-obese and inactive postmenopausal women a comparable 6%-7% weight loss was achieved by diet-only or mainly by exercise and showed improvements in physical and mental HRQoL domains, but results were not statistically significant in either the diet or exercise group. However, a modest weight loss does lead to a positive change in self-perceived health status. This effect was significantly larger with exercise-induced weight loss than with comparable diet-induced weight loss. TRIAL REGISTRATION ClinicalTrials.gov NCT01511276.
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Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk.
Nimptsch, K, Aleksandrova, K, Boeing, H, Janke, J, Lee, YA, Jenab, M, Bueno-de-Mesquita, HB, Jansen, EH, Tsilidis, KK, Trichopoulou, A, et al
International journal of cancer. 2015;(5):1181-92
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High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
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Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial.
Travier, N, Velthuis, MJ, Steins Bisschop, CN, van den Buijs, B, Monninkhof, EM, Backx, F, Los, M, Erdkamp, F, Bloemendal, HJ, Rodenhuis, C, et al
BMC medicine. 2015;:121
Abstract
BACKGROUND Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. METHODS This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. RESULTS Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95%CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. CONCLUSIONS A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up. TRIAL REGISTRATION Current Controlled Trials ISRCTN43801571, Dutch Trial Register NTR2138. Trial registered on December 9th, 2009.
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Effect of weight loss, with or without exercise, on body composition and sex hormones in postmenopausal women: the SHAPE-2 trial.
van Gemert, WA, Schuit, AJ, van der Palen, J, May, AM, Iestra, JA, Wittink, H, Peeters, PH, Monninkhof, EM
Breast cancer research : BCR. 2015;(1):120
Abstract
INTRODUCTION Physical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise. METHODS Overweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5-6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry. RESULTS Both the diet (-4.9 kg) and mainly exercise (-5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference -1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared. CONCLUSIONS Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormones. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01511276 . Registered on 12 January 2012.