Specific limitations are addressed in respective experimental chapters. The findings in this thesis are based upon a series of acute, relatively short-term studies, which require careful interpretation if translated directly into clinical practice. It is important to consider that any short-term effect of an intervention needs to be maintained over a longer period of time, and thus this body of work would benefit from longer observational studies assessing the impact of the strategies employed under true free-living conditions and without experimental control parameters. It is suggested that the recommendations generated from this thesis be advertised in-clinic and promoted to type 1 diabetes patients with further follow-up assessment to determine whether such recommendations are effective within a real-world setting, and to establish whether these recommendations impact upon exercise participation, adherence, and improvements in glycaemic control.
Although typical of the vast majority of applied, laboratory-based exercise studies in type 1 diabetes (Bussau et al. 2006, Bussau et al. 2007, West et al. 2010, West et al. 2011, West et al. 2011, Yardley et al. 2012, Davey et al. 2013, Turner et al. 2013, Yardley et al. 2013, Turner et al. 2014, Turner et al. 2014), the sample size employed across chapters was relatively small. However, a power assessment revealed that the number of patients recruited in chapter 3 was sufficient to achieve a statistical power of 80 %, with chapters 4 and 5 achieving a statistical power of 73 %. In addition, this study recruited relatively young, male patients, all in excellent glycaemic control and who were already actively engaged in regular exercise. Caution should be taken when inferring results obtained from this series of studies to the wider diabetes community who may be older, less well controlled, less accustomed to exercise, and treated on different insulin regimens than those employed herein. Indeed, reduced compliance in some patients may make these recommendations difficult to translate and implement. A further limitation is that the strategies employed within this thesis are based upon one exercise model. The glycaemic, metabolic, hormonal and inflammatory responses in type 1 diabetes patients contrast greatly across exercise
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modalities and intensities, and it would therefore be inappropriate to apply these findings to a range of different exercises. Nevertheless, these limitations should not detract from the clinical importance of these findings as patients and clinicians can tailor these strategies based on individual glycaemic responses, treatment regimens, and exercise preferences.
It would be advantageous to follow on from this body of work by investigating wider markers of glycaemic control and diabetes management. Although a fairly broad ranging and comprehensive assessment of the deeper implications arising from these interventions was conducted, due to financial resources, it was only possible to measure two inflammatory cytokines, with a limited number of hormones and metabolites. It would be of great interest, and of potential importance, to determine the deeper physiological mechanisms behind these findings, with an investigation into liver and muscle to determine specific effects on both glucose output and storage, as well as the interplay between these tissues in their role for late-onset hypoglycaemia. To strengthen the clinical application of these strategies it would be beneficial to investigate more global pathological markers for cardiovascular health, such as lipoproteins, hypertension, and endothelial progenitor cells.
6.7 Conclusions
The findings in this thesis have demonstrated:
1. Reducing the dose of rapid-acting insulin administered after exercise, whilst under conditions of heavily reduced pre-exercise rapid-acting insulin dose protects patients for a total of 8 hours after exercise. During this time, patients may experience periods of post- prandial hyperglycaemia, but are not exposed to other metabolic, counter-regulatory hormonal or inflammatory disturbances. Beyond this time, risk of late-onset hypoglycaemia remains. This fully addresses aims 1 and 2 (section 1.10).
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2. The composition of foods consumed after evening exercise carry important implications for type 1 diabetes patients. Specifically, consuming foods that elicit a low GI in the post- exercise period, whilst employing reductions in pre- and post-exercise rapid-acting insulin, reduces post-prandial hyperglycaemia whilst maintaining protection from early-onset hypoglycaemia for a total of 8 hours after exercise. During this time, a high GI meal was shown to increase inflammatory markers, whereas a low GI meal completely prevented this rise and was not associated with any other metabolic or counter-regulatory disturbance. Beyond this time, risk of late-onset nocturnal hypoglycaemia remains. In addition, acute prandial adjustments to rapid-acting insulin and food composition carry implications for appetite, whereby a low GI post-exercise meal induces greater sensations of hunger and lower feelings of satiety early into the post-prandial period. This fully addresses aims 3, 4, and 5 (section 1.10).
3. Combining acute prandial adjustments in rapid-acting insulin and food composition with a reduction in the amount of basal dose administered over the course of an exercise day offers complete protection from hypoglycaemia for a total of 24 hours after exercise. In addition, this strategy does not augment ketonaemia, does not raise inflammatory markers IL-6 and TNF-α above fasted rested concentrations, and is not associated with any other hormonal or metabolic disturbances. In addition, this strategy carries important implications for next day glycaemic control and appetite regulation. This fully addresses aims 6 and 7 (section 1.10).
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Aerobic exercise (~45 minutes of moderate-to- vigorous intensity)
Figure 6.0. Schematic of recommended course of action for preventing exercise-induced hypoglycaemia. Breakfast: carbohydrate- based meal (1.3g.carbohydrate.kg-1) Lunch: carbohydrate-based meal (1.3g.carbohydrate.kg-1) 60 minutes pre-exercise: carbohydrate-based meal (1.0g.carbohydrate.kg-1) 60 minutes post-exercise: carbohydrate-based meal (1.0g.carbohydrate.kg-1) Reduced pre-exercise: rapid-acting insulin analogue (~25% dose) Reduced post-exercise rapid-acting insulin analogue (50% dose)
Omit rapid-acting insulin analogue
240 minutes post-exercise: carbohydrate-based bedtime snack (0.3g.carbohydrate.kg-1)
Full dose of rapid-acting insulin analogue Full dose of rapid-acting
insulin analogue Reduced total basal insulin
administration (~80% dose)
Breakfast: carbohydrate- based meal (1.3g.carbohydrate.kg-1)
Full dose of rapid-acting insulin analogue Resume normal basal
insulin administration (~100% dose) Sleep
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CHAPTER 7
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