Disease progression in newly diagnosed Type 2 Diabetes Mellitus patients: a statistical analysis using Clinical Practice Research Datalink (CPRD)

Abstract Type 2 Diabetes Mellitus is a serious disease with a long duration and considerable associated morbidity. It affects a significant proportion of populations around the world irrespective of economic status and its prevalence is increasing despite the efforts of clinicians, researchers, public health professionals and policy makers. Most epidemiologic research has focused on exploring the risk factors associated with this disease. However the present research aims to increase understanding of the progression of the disease from initial diagnosis to death. Aims The aims of this thesis, from a clinical perspective, are to (a) evaluate the trajectory of blood pressure as the disease progresses from initial diagnosis to death in a large longitudinal database of newly diagnosed type 2 diabetes mellitus patients;, (b) within sub-cohorts based on body mass index at time of diagnosis, explore HbA1c trajectories from diagnosis to death, particularly the association with treatment intensity; (c) examine the 'obesity paradox'; and (d) investigate gender specific effects of smoking on the risks of cardiovascular diseases. In addition the thesis explores methodological issues arising with the use of large longitudinal datasets, in particular issues relating to missing data and the effectiveness of multiple imputation as a technique to correct for this.