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- All Subjects: Cardiovascular Health
- All Subjects: Chemotherapy
- Creators: Angadi, Siddhartha
- Creators: Al-Nakkash, Layla
- Creators: Bolch, Charlotte
Description
Walking interventions focused on increasing step counts are typically associated with salutary effects on glycemia, fasting insulin, insulin resistance and blood lipids which may be in turn associated with improvements in cardiorespiratory fitness (peak oxygen uptake – VO2peak) and vascular stiffness. We hypothesized that a novel 4-month, behavioral economics-based walking intervention would have favorable effects on glucose homeostasis and blood lipids and that these in turn would be related to VO2peak and vascular stiffness (carotid femoral pulse wave velocity – cfPWV).
We carried out secondary analyses on a subsample of sedentary, overweight/obese adults who participated in a 4-month, 2x2, randomized-controlled walking intervention examining the effects of goal setting (static v. adaptive goals) and rewards (immediate v. delayed) on steps/day (N=96). Fasting blood samples (n=58) were collected from participants before and after the intervention. Premenopausal females were in the follicular phase of their menstrual cycles. Lipid and glucose levels were measured using an automated chemistry analyzer, while insulin was measured using radio-immunoassay. Homeostatic model of insulin resistance (HOMA-IR) was calculated using the following formula (HOMA-IR=glucose x insulin / 405). We examined associations [partial correlations (adjusted for age)] between changes in blood biomarkers and VO2peak and cfPWV, irrespective of group, and we used linear mixed models to examine between-group differences in levels of and change in biomarker outcomes.
Groups did not differ in overall levels of, or degree of change in, biomarker outcomes (all p>0.05). Mean changes, irrespective of group, in biomarkers were as follows: glucose Δ= 0.74± 4.5mg/dl; insulin Δ= 0.09 ± 4.1 µU/ml; total cholesterol Δ= 0.24 ± 20.6 mg/dl; HDL-C Δ= 0.27 ± 5.1 mg/dl; LDL-C Δ= 1.3 ± 19.9 mg/dl; triglycerides Δ= 1.7 ± 27.2 mg/dl; HOMA-IR Δ = -.0548 ± 1.05). We found no significant associations between change in biomarker levels and change in VO2peak or change in cfPWV (all correlation coefficients < 0.15; p > 0.05).
A 4-month, behavioral economics-based mHealth intervention focused on increasing steps/day did not bring about favorable changes on markers of glycemia, insulin resistance and blood lipids.
We carried out secondary analyses on a subsample of sedentary, overweight/obese adults who participated in a 4-month, 2x2, randomized-controlled walking intervention examining the effects of goal setting (static v. adaptive goals) and rewards (immediate v. delayed) on steps/day (N=96). Fasting blood samples (n=58) were collected from participants before and after the intervention. Premenopausal females were in the follicular phase of their menstrual cycles. Lipid and glucose levels were measured using an automated chemistry analyzer, while insulin was measured using radio-immunoassay. Homeostatic model of insulin resistance (HOMA-IR) was calculated using the following formula (HOMA-IR=glucose x insulin / 405). We examined associations [partial correlations (adjusted for age)] between changes in blood biomarkers and VO2peak and cfPWV, irrespective of group, and we used linear mixed models to examine between-group differences in levels of and change in biomarker outcomes.
Groups did not differ in overall levels of, or degree of change in, biomarker outcomes (all p>0.05). Mean changes, irrespective of group, in biomarkers were as follows: glucose Δ= 0.74± 4.5mg/dl; insulin Δ= 0.09 ± 4.1 µU/ml; total cholesterol Δ= 0.24 ± 20.6 mg/dl; HDL-C Δ= 0.27 ± 5.1 mg/dl; LDL-C Δ= 1.3 ± 19.9 mg/dl; triglycerides Δ= 1.7 ± 27.2 mg/dl; HOMA-IR Δ = -.0548 ± 1.05). We found no significant associations between change in biomarker levels and change in VO2peak or change in cfPWV (all correlation coefficients < 0.15; p > 0.05).
A 4-month, behavioral economics-based mHealth intervention focused on increasing steps/day did not bring about favorable changes on markers of glycemia, insulin resistance and blood lipids.
ContributorsHook, Benjamin E. (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
As the 7th leading cause of death in the world, with over 1.6 millions deaths attributed to it in 2016 alone, diabetes mellitus has been a rising global health concern. Type 1 diabetes is caused by lack of insulin production whereas type 2 diabetes is caused by insulin resistance. Both types of diabetes lead to increased glucose levels in the body if left untreated. This, in turn, leads to the development of a host of complications, one of which is ischemic heart disease. Accounting for the death of 16% of the world’s population, ischemic heart disease has been the leading cause of death since 2000. As of 2019, deaths from this disease have risen from 2 million to over 8.9 million globally. While medicine exists to counter the negative outcomes of diabetes mellitus, lower income nations suffer from the lack of availability and high costs of these medications. Therefore, this systematic review was performed to determine whether a non-medicinal treatment could provide similar therapeutic benefits for individuals with diabetes. Genistein is a phytoestrogen found in soy-based products, which has been potentially linked with preventing diabetes and improving diabetes-related symptoms such as hyperglycemia and abnormal insulin levels. We searched PubMed and SCOPUS using the terms ‘genistein’, ‘diabetes’, and ‘glucose’ and identified 32 peer-reviewed articles. In general, preclinical studies demonstrate that genistein decreases body weight as well as circulating glucose and triglycerides concentrations while increasing insulin levels and insulin sensitivity. It also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies of genistein in general reported no significant relationship between genistein and body mass, circulating glucose, serum insulin, A1C concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity, delay type 2 diabetes onset and improve serum triglyceride levels. In summary, preclinical and clinical studies suggest that genistein may help delay onset of type 2 diabetes and improve several symptoms associated with the disease. By translating these findings into clinical settings, genistein may offer a cost effective natural approach at mitigating complications associated with diabetes, although additional research is required to confirm these findings.
ContributorsJain, Rijul (Author) / Sweazea, Karen (Thesis director) / Al-Nakkash, Layla (Committee member) / Bolch, Charlotte (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-04-16
Description
Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and loss of cardiorespiratory fitness. These negative outcomes have implications for early morbidity and mortality. The purpose of this thesis was to test the hypothesis that high-intensity exercise preconditioning (exercise commenced prior to initiating chemotherapy and continued throughout treatment cycles) preserves health-related outcomes in breast cancer patients treated with anthracycline-containing chemotherapy. Here, we present a subset of preliminary data from an ongoing trial (NCT02842658) that is focused on VO2peak and skeletal muscle outcomes from the first 10 participants that have enrolled in the trial. Breast cancer patients (N=10; 50 ± 11 y; 168 ± 4 cm; 92 ± 37 kg; 32.3 ± 12.3 kg/m2) scheduled to receive anthracycline-containing chemotherapy were randomly assigned to one of two interventions: 1) exercise preconditioning, (3 days per week of supervised exercise throughout treatment) or 2) standard of care (attention-control). Pre-testing occurred 1-2 week prior to chemotherapy. The interventions were initiated 1 week prior to chemotherapy and continued throughout anthracycline treatment. Post-testing occurred 3-7 days following the last anthracycline treatment. VO2peak (L/min) was reduced by 16% in the control group (P < 0.05), whereas VO2peak was preserved in the exercise preconditioning group. Trends for greater preservation and/or improvement in the exercise preconditioning group were also observed for lean body mass and peak heart rate. Hand grip strength was not changed in either group (P > 0.05). Both groups demonstrated an increase in ultrasound-derived echogenicity measures of the vastus lateralis (P < 0.05), indicating changes in the composition of the skeletal muscle during treatment. These preliminary data highlight that exercise preconditioning may serve as a strategy to preserve cardiorespiratory fitness and perhaps lean mass during anthracycline treatment of breast cancer. There remains a need for larger, definitive clinical trials to identify strategies to prevent the array of chemotherapy-induced toxicities that are observed in breast cancer patients treated with anthracyclines.
ContributorsCasey, Kathleen (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Dickinson, Jared (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05