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WISER Survivor Trial: Combined Effect of Exercise and Weight Loss Interventions on Adiponectin and Leptin Levels in Breast Cancer Survivors with Overweight or Obesity.
Lin, D, Sturgeon, KM, Gordon, BR, Brown, JC, Sears, DD, Sarwer, DB, Schmitz, KH
Nutrients. 2023;(15)
Abstract
Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to leptin (A:L) ratio. The four-arm randomized controlled WISER Survivor trial examined the 12-month intervention effects of exercise, weight loss, and the combination of exercise and weight loss on adipokine levels among breast cancer survivors (n = 339) with overweight or obesity. Compared with Control, the Combination of Exercise and Weight Loss decreased leptin levels (-35.9%; 95% CI: -46.8%, -25.0%) and increased A:L ratio (11.6%; 95% CI: 5.6%, 17.6%) but did not change adiponectin levels (4.1%; 95% CI: -3.1%, 11.2%). Compared with Control, Weight Loss Alone decreased leptin levels (-35.6%; 95% CI: -46.6%, -24.5%) and increased A:L ratio (10.6%; 95% CI: 4.7%, 16.5%) but did not change adiponectin levels (0.9%; 95% CI: -6.0%, 7.9%). Compared with Control, Exercise Alone did not change leptin levels, adiponectin levels, or A:L ratio. In analyses that consolidated intervention groups, compared with Control, weight loss of ≥5% decreased leptin levels (p trend < 0.01) and increased A:L ratio (p trend < 0.01) but did not alter adiponectin levels (p trend = 0.53). Weight loss, with or without exercise, was associated with decreased leptin levels in breast cancer survivors with overweight or obesity. Improvements in the adipokine secretion profile (A:L ratio) were primarily driven by a weight loss-induced change in leptin levels.
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The effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors.
Brown, JC, Sturgeon, K, Sarwer, DB, Troxel, AB, DeMichele, AM, Denlinger, CS, Schmitz, KH
Breast cancer research and treatment. 2023;(1):109-117
Abstract
PURPOSE Cancer and its treatments accelerate biological aging. This analysis tested the hypothesis that exercise and diet reduce oxidative stress and prevent telomere shortening in breast cancer survivors. METHODS In a 2 × 2 factorial design, 342 breast cancer survivors who were insufficiently physically active and had overweight or obesity at enrollment were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. The endpoints of this analysis were the change from baseline to week 52 in 8-iso-prostaglandin F2α (8-iso-PGF2α) and lymphocyte telomere length. RESULTS Baseline telomere length was shorter than age-adjusted normative values (median difference: - 1.8 kilobases; 95% CI - 2.4, - 1.1); equivalent to 21 years (95% CI 17, 25) of accelerated chronological aging. Compared to control, exercise alone did not change 8-iso-PGF2α [9.9%; 95% confidence interval (CI) - 1.0, 20.8] or telomere length (13.8%; 95% CI - 15.6, 43.3). Compared to control, diet alone was associated with reduced 8-iso-PGF2α (- 10.5%; 95% CI - 19.5, - 1.5) but did not change telomere length (12.1%; 95% CI - 17.2, 41.3). Compared to control, exercise plus diet was associated with reduced 8-iso-PGF2α (- 9.8%; 95% CI - 18.7, - 0.9) but did not change telomere length (- 8.5%; 95% CI - 32.1, 15.2). Change in 8-iso-PGF2α did not correlate with change in telomere length (r = 0.07; 95% CI - 0.07, 0.20). CONCLUSION In breast cancer survivors, diet alone or exercise plus diet were associated with reduced oxidative stress but did not change telomere length. This analysis may inform future trials that aim to optimize healthy aging in cancer survivors.
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The effects of exercise and diet on sex steroids in breast cancer survivors.
Brown, JC, Sturgeon, K, Sarwer, DB, Troxel, AB, DeMichele, AM, Denlinger, CS, Schmitz, KH
Endocrine-related cancer. 2022;(8):485-493
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Insufficient physical activity and obesity are associated with an increased risk of cancer recurrence and death in breast cancer survivors. Sex steroid hormones may mediate these associations. This study tested the hypothesis that exercise and diet, as compared to control, favorably change sex steroid hormones. This analysis of data from a subset of participants in a 2 × 2 factorial trial compares 269 postmenopausal breast cancer survivors who were insufficiently physically active and had overweight or obesity and were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. Secondary sex steroid hormone endpoints included estradiol, sex hormone-binding globulin (SHBG), and testosterone. Treatment effects were quantified using a mixed model for repeated measures. Compared to control, exercise alone did not significantly change estradiol (-1.9%; 95% CI: -12.6, 8.8), SHBG (2.4%; 95% CI: -9.9, 14.6), or testosterone (1.2%; 95% CI: -12.2, 14.5). Compared to control, diet alone did not significantly change estradiol (-7.8%; 95% CI: -17.6, 1.9), SHBG (8.2%; 95% CI: -4.2, 20.6), or testosterone (-0.8%; 95% CI: -13.6, 12.0). Compared to control, exercise plus diet did not significantly change estradiol (-6.3%; 95% CI: -16.3, 3.6), SHBG (8.8%; 95% CI: -4.0, 21.7), or testosterone (-5.3%; 95% CI: -18.0, 7.4). In postmenopausal breast cancer survivors who were insufficiently physically active and had overweight or obesity, randomization to exercise alone, diet alone, or exercise plus diet did not statistically significantly change sex steroid hormone concentrations at week 52.
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WISER Survivor Trial: Combined Effect of Exercise and Weight Loss Interventions on Insulin and Insulin Resistance in Breast Cancer Survivors.
D'Alonzo, NJ, Qiu, L, Sears, DD, Chinchilli, V, Brown, JC, Sarwer, DB, Schmitz, KH, Sturgeon, KM
Nutrients. 2021;(9)
Abstract
Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical trial examining the relative effect of exercise, weight loss and combined exercise and weight loss interventions on insulin and insulin resistance. The weight loss and combined intervention groups showed significant reductions in levels of: insulin, C-peptide, homeostatic model assessment 2 (HOMA2) insulin resistance (IR), and HOMA2 beta-cell function (β) compared to the control group. Independent of intervention group, weight loss of ≥10% was associated with decreased levels of insulin, C-peptide, and HOMA2-IR compared to 0-5% weight loss. Further, the combination of exercise and weight loss was particularly important for breast cancer survivors with clinically abnormal levels of C-peptide.
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Lifestyle modifications alone or combined with hormonal contraceptives improve sexual dysfunction in women with polycystic ovary syndrome.
Steinberg Weiss, M, Roe, AH, Allison, KC, Dodson, WC, Kris-Etherton, PM, Kunselman, AR, Stetter, CM, Williams, NI, Gnatuk, CL, Estes, SJ, et al
Fertility and sterility. 2021;(2):474-482
Abstract
OBJECTIVE To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population, and to assess the impact of common PCOS treatments on sexual function. DESIGN Secondary analysis of a randomized controlled trial, oral contraceptive pills and weight loss in PCOS. SETTING Two academic medical centers. PATIENTS Women with PCOS (N = 114) defined by the Rotterdam criteria. INTERVENTIONS Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURES Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores after 16 weeks. RESULTS There was no change in total FSFI or FSDS-R score in any treatment group; however, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period. Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle and Combined treatments. There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores. CONCLUSION(S): Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments for PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial. CLINICAL TRIAL REGISTRATION NUMBER NCT00704912.
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Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS.
Shah, A, Dodson, WC, Kris-Etherton, PM, Kunselman, AR, Stetter, CM, Gnatuk, CL, Estes, SJ, Allison, KC, Sarwer, DB, Sluss, PM, et al
The Journal of clinical endocrinology and metabolism. 2021;(1):108-119
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OBJECTIVE To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic). DESIGN Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29). MATERIALS AND METHODS Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes. RESULTS Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P < 0.001). None of the analytes were significantly affected by Lifestyle, whereas the effects of Combined were similar to OCPs alone, although attenuated. Oxyntomodulin was significantly positively associated with the change in total ovarian volume (rs = 0.27; 95% CI: 0.03, 0.48; P = 0.03) and insulin sensitivity index (rs = 0.48; 95% CI: 0.27, 0.64; P < 0.001), and it was inversely correlated with change in area under the curve (AUC) glucose [rs = -0.38; 95% CI: -0.57, -0.16; P = 0.001]. None of the hormonal changes were associated with live birth, only Activin A was associated with ovulation (risk ratio per 1 ng/mL increase in change in Activin A: 6.0 [2.2, 16.2]; P < 0.001). CONCLUSIONS In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth.
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A randomized trial of exercise and diet on body composition in survivors of breast cancer with overweight or obesity.
Brown, JC, Sarwer, DB, Troxel, AB, Sturgeon, K, DeMichele, AM, Denlinger, CS, Schmitz, KH
Breast cancer research and treatment. 2021;(1):145-154
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PURPOSE Obesity increases the risk of cancer recurrence and death in survivors of breast cancer. This study tested the hypothesis that exercise alone, diet alone, and the combination of exercise plus diet reduce body weight and improve body composition in survivors of breast cancer. METHODS In this 2 × 2 factorial trial, 351 survivors of breast cancer with overweight or obesity were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. Endpoints included body weight and body composition measured by dual-energy x-ray absorptiometry. RESULTS After 52 weeks, compared with control, diet alone [- 5.39 kg (95% CI - 7.24, - 3.55);- 6.0% (95% CI - 8.0, - 3.9)] and exercise plus diet [- 6.68 kg (95% CI - 8.46, - 4.90);- 7.4% (95% CI - 9.4, - 5.4)] reduced body weight; exercise alone did not change body weight. Compared with control, diet alone [- 3.59 kg (95% CI - 5.00, - 2.17)] and exercise plus diet [- 4.28 kg (95% CI - 5.71, - 2.84)] reduced fat mass; exercise alone did not change fat mass. Compared with control, diet alone [- 0.82 kg (95% CI - 1.50, - 0.15)] and exercise plus diet [- 1.24 kg (95% CI - 1.92, - 0.56)] reduced lean mass; exercise alone did not change lean mass. Compared with control, exercise alone, diet alone, and exercise plus diet did not change bone mineral density. CONCLUSION In survivors of breast cancer with overweight or obesity, diet alone or diet plus exercise produced clinically meaningful weight loss at week 52. The majority of weight loss was fat mass.
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A randomized trial of exercise and diet on health-related quality of life in survivors of breast cancer with overweight or obesity.
Brown, JC, Sarwer, DB, Troxel, AB, Sturgeon, K, DeMichele, AM, Denlinger, CS, Schmitz, KH
Cancer. 2021;(20):3856-3864
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BACKGROUND Obesity is a chronic, relapsing, and progressive disease; it is associated with poor health-related quality of life (HRQOL) in survivors of breast cancer. METHODS In this 2 × 2 factorial trial, 351 survivors of breast cancer with overweight or obesity were randomized to 1 of 4 treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. HRQOL end points were measured at baseline and at week 52 using the 36-Item Medical Outcomes Survey-Short Form (SF-36). Repeated measures analysis of covariance quantified the estimated treatment difference (ETD). RESULTS At baseline, participants had a mean (SD) age of 59.4 years (8.7), body mass index of 34.0 kg/m2 (5.9), and 71 participants (20.2%) self-reported fair or poor general health. After 52 weeks, compared with control, the exercise plus diet improved the physical health summary score (ETD: 5.39; 95% CI, 0.55-10.22); exercise alone (ETD: -1.91; 95% CI, -6.60 to 2.79) and diet alone (ETD: 3.16; 95% CI, -1.52 to 7.83) did not change the physical health summary score. Compared with control, exercise alone (ETD: -0.27; 95% CI, -6.60 to 2.79), diet alone (ETD: 3.25; 95% CI, -1.41 to 7.91), and the exercise plus diet (ETD: 1.75; 95% CI, -2.90 to 6.39) did not change the mental health summary score. Exercise alone did not impact any HRQOL subscale; diet alone improved the vitality subscale; exercise plus diet improved the physical functioning, role-physical and vitality subscales. CONCLUSION In survivors of breast cancer with overweight or obesity, exercise plus diet improved select HRQOL end points at week 52.
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Obesity in the Workplace: Impact, Outcomes, and Recommendations.
Yarborough, CM, Brethauer, S, Burton, WN, Fabius, RJ, Hymel, P, Kothari, S, Kushner, RF, Morton, JM, Mueller, K, Pronk, NP, et al
Journal of occupational and environmental medicine. 2018;(1):97-107
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OBJECTIVE To conduct a comprehensive literature review to develop recommendations for managing obesity among workers to improve health outcomes and to explore the impact of obesity on health costs to determine whether a case can be made for surgical interventions and insurance coverage. METHODS We searched PubMed from 2011 to 2016, and CINAHL, Scopus, and Cochrane Registry of Clinical Trials for interventions addressing obesity in the workplace. RESULTS A total of 1419 articles were screened, resulting in 275 articles being included. Several areas were identified that require more research and investigation. CONCLUSIONS Our findings support the use of both lifestyle modification and bariatric surgery to assist appropriate patients in losing weight.
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Project HELP: a Remotely Delivered Behavioral Intervention for Weight Regain after Bariatric Surgery.
Bradley, LE, Forman, EM, Kerrigan, SG, Goldstein, SP, Butryn, ML, Thomas, JG, Herbert, JD, Sarwer, DB
Obesity surgery. 2017;(3):586-598
Abstract
BACKGROUND Weight regain following bariatric surgery is common and potentially compromises the health benefits initially attained after surgery. Poor compliance to dietary and physical activity prescriptions is believed to be largely responsible for weight regain. Patients may benefit from developing specialized psychological skills necessary to engage in positive health behaviors over the long term. Unfortunately, patients often face challenges to physically returning to the bariatric surgery program for support in developing and maintaining these behaviors. Remotely delivered interventions, in contrast, can be conveniently delivered to the patient and have been found efficacious for a number of health problems, including obesity. To date, they have received little attention with bariatric surgery patients. The study aimed to evaluate a newly developed, remote acceptance-based behavioral intervention for postoperative weight regain. METHODS Patients at least 1.5 years out from surgery who experienced postoperative weight regain were recruited to receive the 10-week intervention. Participants were assessed at baseline, mid-treatment, post-treatment, and at 3-month follow-up. RESULTS Support for the intervention's feasibility and acceptability was achieved, with 70 % retention among those who started the program and a high mean rating (4.7 out of 5.0) of program satisfaction among study completers. On average, weight regain was reversed with a mean weight loss of 5.1 ± 5.5 % throughout the intervention. This weight loss was maintained at 3-month follow-up. Significant improvements in eating-related and acceptance-based variables also were observed. CONCLUSIONS This pilot study provides initial support for the feasibility, acceptability, and preliminary efficacy of a remotely delivered acceptance-based behavioral intervention for postoperative weight regain.