Characterising the Clinical Heterogeneity of Type 1 Diabetes

Abstract

There is growing evidence that type 1 diabetes is not a single disease with a predictable course, but rather comprises a number of disease phenotypes characterised by distinct immunologic, genetic and metabolic features. Indeed, a recent shift towards onset in patients at lower genetic risk highlights the increasing importance of environmental and metabolic factors in disease pathogenesis. These factors may contribute to the development of microvascular complications and alter mortality risk. This thesis aims to characterise the heterogeneity of type 1 diabetes and its complications by describing four cohorts diagnosed between 1973 and 2014. Findings from this thesis contribute to understanding the heterogeneity of T1D and its disease course, identification of novel risk factors for microvascular complications and early risk factors for increased mortality. These findings may allow appropriate risk stratification and targeted intervention to prevent type 1 diabetes onset, the development of microvascular complications and to reduce mortality