The role of diet and exercise in insulin action and glycaemic control
Creators: name: Lockhead, Zak
Publisher: name: Loughborough University
Year: 2022
Subjects: classificationCode: 420799
subject: Sports science and exercise not elsewhere classified

description: Excessive caloric intake and/or insufficient physical activity has increased global levels of obesity, which is a significant risk factor for several comorbidities including insulin resistance and type 2 diabetes. However, at present, the pathogenesis of insulin resistance is not fully understood. Lipid excess can rapidly impair whole-body insulin sensitivity and glycaemic control. As a result, the model of high-fat overfeeding has frequently been applied in rodents and humans to study the early progression of insulin resistance. To date, few studies have overfed with excessive carbohydrate. This is problematic, as work cannot determine whether it is caloric overload or specific macronutrient intake that leads to negative alterations in metabolic health. Accordingly, the early metabolic consequence of high-carbohydrate/high- sugar overfeeding requires further investigation. In addition, regular exercise can be an important lifestyle modification for improving metabolic health and preventing insulin resistance. It is well known that regular endurance exercise can lead to greater insulin sensitivity. However, less is known about the effect of chronic resistance exercise on insulin sensitivity and glycaemic control. Therefore, the aims of this thesis were to investigate the effect of high-fat and high-carbohydrate overfeeding on insulin sensitivity and glycaemic control and to examine the chronic effects of endurance- and resistance- exercise on metabolic health.In Chapter 3, a 14 d hyperenergetic (130% estimated energy requirement), high-fat (67% total fat) or high-carbohydrate (72% total carbohydrate) diet was used to examine the effect of overfeeding with different macronutrients on whole-body insulin sensitivity and glycaemic control. Overfeeding led to significant increases in body mass and significant increases in fasting insulin resistance (assessed via fasting serum insulin and HOMA-IR) regardless of the type of macronutrient consumed. Samples from this study were analysed in Chapter 4, in which we assessed the hepatokine response to overfeeding. LECT2 increased in response to both dietary interventions. Notably, the increase in LECT2 was significantly correlated with decreases in fasting insulin sensitivity, implicating this hepatokine in early reductions in metabolic health. In contrast, FGF21 was unresponsive to overfeeding. In chapter 5, endurance- and resistance-trained participants were recruited for comparison of fasting metabolic health profiles. We observed that whole-body insulin sensitivity, glycaemic control and lipid profile was similar between both types of athlete. Furthermore, all metabolic markers were within the healthy reference range, suggesting that both exercise modalities may be a viable lifestyle modification for maintaining/improving metabolic health.Collectively, the studies in this thesis demonstrate that short-term energy excess, rather than the specific type of macronutrient consumed, can lead to deteriorations in whole-body insulin sensitivity in response to 14 d of overfeeding. Our work also suggests that the hepatokine LECT2 may be implicated in early overfeeding-induced decreases in insulin sensitivity. Furthermore, we have demonstrated that metabolic health was similar between endurance- and resistance-trained participants, suggesting that both exercise modalities may reduce risk of insulin resistance.