[Truncated abstract] Type 1 Diabetes is emerging as a significant public health problem faced by nearly every country in the world. It has major economic and social implications with considerable burden of illness. Approximately 140,000 Australians have been diagnosed with T1DM with an annual increase in incidence rate of 3% per year, comparable to the overall global increase. The management of T1DM requires insulin therapy which places considerable burden on the patient and their carers. Coping with daily insulin injections, dietary changes, modification of physical activity and vigilant monitoring of blood glucose levels, will impact on patient?s quality of life. The optimum goal for the treatment of type 1 diabetes is to safely achieve near-normal glycaemia and failure to maintain this goal accelerates the progression of the devastating long term complications of diabetes. Unfortunately attempts to achieve near normal glycaemia are limited by the risk of excessive lowering of blood glucose levels and hypoglycaemia remains a major barrier to strict glucose control of diabetes. In general this thesis focuses on two fundamental issues related to the epidemiology of severe hypoglycaemia. Namely, methodological consideration when analysing prospective observational data and application of the most robust methodology. A prospective open cohort study of the Princess Margaret Hospital diabetes clinic established in 1992, with 99% case ascertainment was used. This hospital is the only paediatric referral centre for type 1 diabetes and every child diagnosed in the state of Western Australia is treated at this centre. ... The results of this study showed that severe hypoglycaemia remains a major problem and recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycaemia. The study in chapter 7 investigates genetic risk factors related to severe hypoglycaemia. A significant relationship where the presence of the iv deletion (D) allele of the angiotensin-converting enzyme (ACE) increases risk of severe hypoglycaemia has been reported. This study concludes that the presence of D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia. In an attempt to optimize glycemic control, patients may suffer multiple episodes of severe hypoglycaemia which can adversely affect quality of life as well as educational and intellectual disadvantage. The study in chapter 8 investigates the factors related to recurrent severe hypoglycaemia. A rigorous and informative time-to-event approach is used to account for within child correlation, staggered enrolment and timevarying covariates. This allows important risk factors to change over time. Preschool children have an increased risk of experiencing recurrent severe hypoglycaemia. The findings of this thesis highlights the importance of selecting appropriate analytical methodology to identify risk factors associated with severe hypoglycaemia and also to dismiss factors that had previously been thought to be important. This will help in formulating management plans in order to limit the impact of severe hypoglycaemia.

Diss. (sammanfattning) Linköping : Univ. / Härtill 6 uppsatser.