Factors influencing heterogeneity in anthropometric and metabolic responses to structured lifestyle interventions
Finucane, Francis Martin
Finucane, Francis Martin
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Publication Date
2024-04-16
Type
Thesis
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Abstract
The rising prevalence of obesity is a significant burden on affected individuals, on healthcare systems and on society. Diet and physical activity are critical determinants of body weight and obesity risk, and lifestyle modification is the cornerstone of the therapeutic approach to obesity. However, there is substantial inter-individual variation in responses to lifestyle modification. In this work, I examine some of the factors associated with variations in anthropometric and metabolic responses to structured lifestyle modification programmes. Firstly, I conducted a prospective cohort study of patients with severe obesity completing a structured diet and exercise programme, noting that older patients, males and those with lower levels of depression were more likely to complete the programme, and were more likely to achieve ≥5% weight loss. I found strong and consistent associations between the amount of weight lost and the magnitude of improvements in markers of mental, metabolic and cardiovascular health. Secondly, I completed a post hoc analysis of the Hertfordshire Physical Activity Trial, describing the effect of a supervised, structured 12-week aerobic exercise intervention on objectively measured physical activity energy expenditure in healthy older adults. There was no significant effect of the exercise intervention on overall average physical activity, but there was an effect on the three days of the week that the exercise sessions took place, suggesting that the frequency of exercise bouts, rather than their intensity or duration, may not have been adequate to exact an overall effect of the intervention. Thirdly, I conducted a cohort analysis from the same trial, describing a strong and consistent association between physical activity energy expenditure and body fat, cardiovascular risk and various measures of insulin resistance, in healthy older adults. However, changes in physical activity were only associated with improvements in some of those outcomes, suggesting that the metabolic benefits of physical activity take longer than 12 weeks to become apparent. Fourthly, in a retrospective cohort study of adults with severe obesity completing a milk-based meal replacement programme, I found that a genetic risk score derived from common polymorphisms associated with central fat distribution was inversely associated with the magnitude of weight loss, the first Irish study to confirm a genetic influence on the response to a dietary intervention. Finally, in a prospective cohort study in patients undergoing the milk diet, I described associations between changes in fasting plasma ketone concentrations and weight loss. This has led to securing research funding from Science Foundation Ireland to explore the relevance of physiological ketosis in predicting and mediating responses to clinical interventions for patients with obesity, at CÚRAM.
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NUI Galway