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ItemSubstituting beta cell function in type 1 diabetesMcAuley, Sybil Anne ( 2017)Matching exogenous insulin dosing to the varying metabolic requirements of people with type 1 diabetes is crucial for optimising health and minimising the burden of diabetes self-care. Advances in insulin formulations, insulin delivery systems and glucose monitoring technology have resulted in improvements in glucose control and in increased automation of therapy. However, subcutaneous insulin administration is significantly limited by its non-physiological delivery. Continuous subcutaneous delivery of rapid-acting insulin analogues via pump is well established in clinical care. Despite this, pharmacokinetic and pharmacodynamic responses to small insulin pump basal rate changes—typical of those implemented in clinical practice—have not previously been established. There is additional complexity associated with exercise due to changes in insulin sensitivity, absorption and action. While blood glucose meters represent a proven technology for point glucose measurement, their use is painful, requires user initiation and does not provide predictive information. These shortcomings are in part addressed by continuous glucose monitoring technology; however, the performance of the present generation of glucose sensors has substantial limitations. Hence, maintenance of glucose homeostasis in type 1 diabetes remains a therapeutic challenge. This research investigated the utility of effectively employing insulin pump and glucose sensor technology to optimise metabolic control and improve diabetes outcomes for adults with type 1 diabetes. This thesis shows that after small insulin pump basal rate changes, there are substantial delays until changes in circulating insulin levels occur. Moreover, for small rate changes of equal magnitude, it takes longer to achieve change in circulating insulin after a rate reduction than after an increase. Adjustment of basal insulin delivery to minimise hypoglycaemia with exercise was investigated. Findings demonstrated that very large reductions in basal insulin delivery are required to achieve a timely decrease in circulating insulin for aerobic exercise; when pre-exercise glucose levels are low-normal, supplemental carbohydrate ingestion may also be necessary to avoid hypoglycaemia. In a cross-sectional study, insulin pump users were observed to have more favourable vascular health profiles than those treated with insulin injections; these differences are possibly explained by multiple factors independent of the insulin delivery modality. To improve glucose sensor performance, a novel sensor combining two distinct sensing methodologies was developed and investigated. Feasibility of the novel sensor was confirmed, and its accuracy compared favourably with glucose sensors available at the time the research was undertaken. This thesis expands the current understanding of insulin delivery via pump and glucose sensing technology for people with type 1 diabetes. Until type 1 diabetes prevention and cure are achieved, the optimisation of insulin dose adjustment in parallel with the further development of glucose sensing technology is still required to mimic healthy pancreatic beta cell function.