Metabolic Flexibility in Children with Obesity: Exercise as a Dynamic Stimulus to Assess Metabolic Health

Abstract

The research in this thesis was completed to advance our knowledge about metabolic flexibility under exercise conditions in children with obesity. The primary objectives of the studies were to determine the validity and reliability of a novel metabolic flexibility test to screen for risk factors associated with type 2 diabetes, including impaired glucose tolerance, dysglycemia, and insulin resistance (Chapter 3 and Chapter 4), and to investigate the effect of 7 days of exercise training on insulin resistance and metabolic flexibility in children with obesity (Chapter 5). Compared to children with normal glucose tolerance, children identified with impaired glucose tolerance did not have reduced metabolic flexibility, which was measured by calculating exogenous carbohydrate oxidative efficiency during exercise (Chapter 3). Despite greater insulin resistance in the children with impaired glucose tolerance, metabolic flexibility was not significantly different between groups. Bivariate analyses showed that metabolic flexibility was not associated with fasting glucose, insulin resistance or beta-cell function in the entire group of participants (Chapter 4). However, when the children were separated by sex, metabolic flexibility was inversely associated with insulin resistance and directly associated with whole body insulin sensitivity index and beta-cell function in boys but not in girls (Chapter 4). The metabolic flexibility test demonstrated good reliability based on an intraclass correlation coefficient of 0.692 (Chapter 4). After 7 days of exercise training in a group of children with obesity, insulin resistance and metabolic flexibility did not improve as hypothesized (Chapter 5). An unexpected observation was the large inter-individual variability in these responses in the early stages of exercise therapy. Altogether, the studies presented in this thesis were the first to examine metabolic flexibility under exercise conditions at baseline and in response to exercise training in children. The studies were also the first to investigate the relationship of metabolic flexibility with fasting glucose and insulin resistance in children, and to assess the reliability of test results when repeating the non-invasive metabolic flexibility test on a separate day. By increasing our general knowledge of metabolic flexibility testing in children, we can better evaluate the clinical utility of the test to screen for risk factors associated with type 2 diabetes in the future.