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Title: Body composition, endocrine abnormalities, and cardiovascular risk in survivors of childhood bone marrow transplantation with total body irradiation : the impact of an exercise intervention
Author: Davis, Nikki Louise
ISNI:       0000 0004 5924 1044
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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Survivors of bone marrow transplant (BMT) with total body irradiation (TBI) in childhood are known to suffer late-effects due to toxicities of malignancy and its treatments including chemotherapy, glucocorticoids and TBI. Well described late-effects include short stature, gonadal failure, growth hormone deficiency (GHD), fatigue and reduced quality oflife (QOL). Emerging late-effects include increased central adiposity, reduced lean mass, increased risk of metabolic syndrome and cardiovascular mortality. Many features are shared with the GHD phenotype but the effects of growth hormone (GH) treatment are unknown. Aims of the research were as follows: - To describe the BMT/TBI phenotype in more detail in reference to body composition, insulin resistance, cytokines and cardiovascular risk markers. To investigate the GH axis in further detail using overnight growth hormone profiles, IGF-l generation tests, and the response to GH treatment over the first year. To examine the HP A axis using overnight cortisol profiles. To investigate the effects of an exercise intervention on body composition, insulin resistance, and cardiovascular risk. Results confirmed increased adiposity and reduced lean mass in BMT/TBI survivors with and without GHD and ameliorated by GH treatment. Increased risk of diabetes, metabolic syndrome and dyslipidaemia were demonstrated. Data showed a high prevalence of GHD in BMT/TBI survivors after adjustment for adiposity and that this persisted into adulthood and evolved with time since BMT/TBI. GH treatment resulted in improved height velocity and body composition but not improved metabolic and cardiovascular risk factors. There were no differences in response to GH treatment between BMT/TBI survivors and controls. The HPA axis studies showed novel changes in BMT/TBI survivors with clear gender differences in free cortisol index levels, including raised overnight levels in male survivors and blunted morning levels in female survivors. The exercise intervention showed improvements in fitness and insulin resistance but not body composition or cardiovascular risk markers. Further studies are required to investigate the mechanism of the development of diabetes and the metabolic syndrome in this group and further secondary prevention strategies are required to improve long-term cardiovascular outcomes
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available