The effect of exercise timing on glycaemic control in individuals with Type 2 diabetes mellitus

Background: Tight glycaemic control is a key target for the management of Type 2 diabetes mellitus (T2DM). Exercise is regarded as an important adjunct treatment and a principal lifestyle consideration for T2DM management. However, the association between the timing of exercise performance and both the timing of meal consumption and diurnal time has only been recently considered having an important role in maintaining glycaemic control. The overarching aim of this thesis therefore was to investigate the importance of exercise time on glycaemic control in individuals with T2DM and at risk of T2DM. Specific Aims: Within this thesis, two systematic reviews were completed to understand the effect of exercise timing on both acute and chronic glycaemic control measures. The aim of Systematic Review One (Chapter 2) was to review the literature related to exercise timing, relative to meal consumption, and glycaemic control in individuals with T2DM. While the aim of Systematic Review Two (Chapter 3) was to assess the literature related to the diurnal timing of exercise performance and glycaemic control in T2DM individuals. In addition, a training study was conducted to examine the chronic effect of the diurnal timing of exercise performance (morning vs. evening) on glycaemic control measures. The study sought to determine the impact of diurnal exercise timing on i) glycaemic control and insulin sensitivity measures (Study Part One: Chapter 4) and; ii) postprandial glucose (PPG) and insulin (PPI) responses (Study Part Two: Chapter 5) in overweight non-T2DM/T2DM individuals enrolled into a 12-week supervised multi-modal exercise training program. Methods: Systematic searches of online databases were performed to identify articles published in English from inception to October 2017 for both systematic reviews. Thereafter, two authors independently extracted data and evaluated the quality of studies using the Cochrane Collaboration Data Collection Form and Cochrane Collaboration Risk of Bias Assessment Tool respectively. A qualitative synthesis was performed on the included studies with the results summarized in tables for both systematic reviews (Chapter 2 and 3). In addition, a training study was conducted to examine the chronic effect of the diurnal timing of exercise performance (morning vs. evening) on glycaemic control measures. In the training study (Chapter 4 and 5), individuals completed a 12-week supervised multi-modal exercise training program (3 days per week; each session: 30 minutes walking protocol and 4 resistance-based exercises for 3 sets of 12-18 repetitions). Results: In Systematic Review One (Chapter 2), a total of 19 (346 participants) randomized controlled trials (RCTS) that employed either an acute crossover (n = 17) or longitudinal parallel-groups (n = 2) design were included in the qualitative synthesis. The main findings of this review were that postprandial exercise performed between 30 to 60 minutes after meal consumption appears to more consistently improve glycemia (glucose concentrations and glucose-AUC) and insulin-AUC when compared to an acute exercise bout performed prior to a meal. In Systematic Review Two (Chapter 3), 18 studies (321 participants: 17 crossover and 2 parallel-groups) were included for qualitative analysis. Comparisons of the studies indicate greater improvements in glucose concentrations when exercise was performed in the morning, however, similar improvements in glucose-AUC were seen for both morning and evening groups. In addition to the large heterogeneity in study design of the included studies, the observations from both systematic reviews were largely based on indirect comparisons between the studies given the limited number of studies that directly investigated the timing of exercise (meal consumption: 3 trials; diurnal timing: nil). Thus, it remains inconclusive to whether i) postprandial exercise is more effective in improving glycaemic control when compared to pre-prandial exercise and ii) morning or evening exercise is more effective for glycaemic control management in T2DM individuals. However, there were no group differences for any variables (all p ≥ 0.4). With regards to the impact of manipulating the diurnal timing of exercise performance on long term glycaemic control (Study Part One: Chapter 4), 12-weeks of multi-modal exercise training significantly reduced (main effect of time: all p < 0.01) glycosylated haemoglobin (amEX vs pmEX: -0.27 vs. -0.25%), fasting glucose (amEX vs pmEX: -0.9 vs. -1.18 mmol/L), fasting insulin (amEX vs pmEX: -23.8 vs. -22.35 pmol/L), HOMA2-IR (both groups: -0.5) and fructosamine (amEX vs. pmEX: -34.5 vs. -29.6 ± 51.2 μmol/L). However, these reductions were not different between the intervention groups for any variables (all p ≥ 0.4). Thus, irrespective of the diurnal timing of exercise training, 12-weeks of multi-modal exercise training significant improved glycaemic control in both overweight non-T2DM and T2DM individuals. However, the diurnal (morning versus evening) timing of exercise training did not result in additional benefits to glycaemic outcomes. Given that tight glycaemic control necessitates the management of both fasting glucose and PPG concentrations, with accumulating evidence suggesting that PPG excursions better predict death from all causes and cardiovascular disease (CVD) compared to fasting glucose alone, Study Part Two (Chapter 5) showed similar results to that of Study Part One with regards to PPG and PPI responses. 12-weeks of multi-modal exercise training significantly reduced (main effect of time, p < 0.01) PPG and PPI concentrations during the mixed meal tolerance test (MMTT), with no group differences observed (p = 0.69). However, a significantly greater reduction in PPG-iAUC was observed for the pmEX group (-78.56 mmol/L) when compared to the amEX group (-33.22 mmol/L) at post-intervention (p = 0.03). Although a trend may exist to indicate that evening exercise performance may have a greater impact on PPG responses, results from Study Part Two indicate similar findings to that of Study Part One, in that the performance of a multi-modal training program is an effective method to improve PPG and PPI responses. However, the diurnal timing of exercise performance may not provide any additional benefits. Conclusions: The findings presented in this thesis provide evidence for effect of strategically manipulating the diurnal timing of exercise performance on glycaemic control for both overweight non-T2DM and T2DM individuals. Despite the diurnal manipulation of exercise timing not indicating any additional benefits for glycaemic control management, this thesis may have provided plausible explanations effect of diurnal timing of exercise on components of glucose variability observed by a T2DM individual on a daily basis. Specifically, morning exercise may potentially lower glucose excursions experienced during the extended dawn phenomenon while evening exercise may potentially allow for an overall reduction in glucose excursions throughout the day by lowering the early morning ‘spike’ in glucose resulting from the dawn phenomenon. This results provides a clinically meaningful explanation for strategically manipulating the timing of exercise performance for glycaemic control management in T2DM individuals, given that, failing to address both the dawn and extended dawn phenomenon has been proposed to potentially contribute to inadequate glycaemic control and increase the progression of diabetes related complications. More importantly, this thesis the performance of regular exercise based on current exercise guidelines is an effective management tool for i) improving glycaemic control and insulin sensitivity; ii) reducing body anthropometric measures and; iii) improving cardiovascular health. This indicates that the consistent performance of exercise is a vital component for both the prevention and management of T2DM.