Couper, JenniferPeña Vargas, AlexiaAnderson, Jemma Jay Angela2021-12-052021-12-052021https://hdl.handle.net/2440/133561The antecedents of clinical cardiovascular disease begin in childhood and accelerate during puberty. Early vascular changes are measurable in children and adolescents who are at increased risk of cardiovascular disease. Vascular health can be measured non invasively using ultrasound. Flow mediated dilatation (FMD) and Glyceryl Trinitrate mediated dilatation (GTN) are measures of endothelial and smooth muscle vascular function respectively. FMD and GTN correlate with coronary atherosclerosis and to traditional cardivovascualr risk factors. Aortic and carotid intima media thickness (aIMT/cIMT) are measures of vascular structure. Intima media thickness of the arteries is a surrogate marker for clinical cardiovascular disease and predicts future cardiovascular events. Type 1 diabetes (T1D) confers a higher risk of cardiovascular morbidity and mortality, even with modern insulin regimens. The increased risk of cardiovascular disease in T1D is multifactorial. It is related to glycaemic control but also to increased insulin resistance. In addition, the population shift to a higher body mass index also affects those with T1D and increases their vascular risk. Therefore I aimed to investigate lifestyle factors which may correlate with vascular health in youth with T1D and whether metformin, an insulin sensitising agent, would improve vascular health over 12 months in children and adolescents with T1D. The specific lifestyle factors investigated included measures of diet, based on a validated food frequency questionnaire, and exercise, using a wearable activity monitor (Senswear device). The metformin intervention was delivered in a randomised, double blind, placebo controlled trial over 12 months in 90 children and adolescents with T1D. There were two relationships identified between lifestyle factors and vascular health. Daily step count, a surrogate marker for activity levels, related to aIMT in youth with T1D. Those with a higher daily step count had better aIMT. Higher dietary sodium intake related to worse vascular smooth muscle function (GTN) in children with T1D. The total dietary sodium intake was also higher than the recommended daily intake with no children having dietary sodium within the recommended levels. Increasing activity and reduction in dietary sodium are practical ways, which may improve vascular health in children and adolescents with T1D. Longitudinal studies are needed to further investigate the relationship between activity, diet and cardiovascular disease prevention in people with T1D. I found that metformin had several measurable outcomes in children and adolescents with T1D. Firstly, it had no impact on FMD which was our primary outcome measure. It did improve GTN which indicates a modest effect on vascular function. There was no change in IMT over 12 months. There was also a reduction in insulin dose over 12 months, in estimated insulin resistance and a transient reduction in HbA1c. These results add to the body of knowledge on using metformin as an adjunct therapy in children and adolescents with T1D. To date, studies have consistently shown a reduction in daily insulin dose and insulin sensitivity in treated individuals with mixed results in relation to vascular health and HbA1c. The benefits of metformin and its good safety profile warrant further consideration of its use during and beyond pubertyenType 1 diabetesvascular healthadolescentchildmetforminexercisedietsodiiumThesis