Maturity onset diabetes of the young: novel insights into the diagnosis, optimal treatment and clinical progression of the condition using biomarkers and new technology.

Our improved understanding of the pathophysiology of diabetes has resulted in an increased complexity in diagnosing the disorder. Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant disorder which represents 2-3% of all cases of diabetes. Traditionally, MODY was associated with a lean phenotype, a lack of pancreatic auto-antibodies and absent features of the metabolic syndrome. However, it is now appreciated that clinical features both between and within MODY pedigrees are heterogeneous. The presence of novel spontaneous mutations further complicates the diagnosis. The description of MODY as a clinical entity is a relatively new phenomenon; as a result the natural progression of the disorder remains ambiguous. In this candidature, I study aspects of the natural progression and clinical management of MODY from the fetal state through the neonatal period into adolescence and finally look at the development of micro and macrovascular complications including atherosclerotic burden in this cohort. The challenge of differentiating MODY from the more common diabetes forms has resulted in much research activity seeking a biomarker which can accurately diagnose MODY. miRNAs offer an exciting possibility in biomarker development. In this thesis I also present the novel findings of urinary miRNAs in MODY mutation carriers. The overarching aim of this thesis is to improve our understanding and the clinical management of this unique population.