published_or_final_version / Community Medicine / Master / Master of Public Health

Type 1 diabetes is an autoimmune disease due to the interaction of genetic and non-genetic factors, leading to an immune response against insulin secreting islet cells. Concordance rates for type 1 diabetes in monozygotic twins vary widely and no single environmental factor has been shown to cause the disease. Therefore, epigenetics has been suggested to play a role in diabetes aetiology. Preliminary results identified DNA methylation changes in CD14+ monocytes from childhood-onset type 1 diabetes which antedated the disease. Following on from this work, this present study was carried out to investigate whole-genome DNA methylation profiles in CD14+CD16- monocytes, CD4+ T cells, CD19+ B cells and buccal cells from 24 monozygotic twin pairs discordant for type 1 diabetes. DNA methylation was profiled using Illumina Infinium HumanMethylation450K BeadChip and analysed using the ChAMP pipeline. Bisulfite sequencing was also carried out on CD4+ cells from four monozygotic twin pairs also discordant for type 1 diabetes. Through bioinformatics analyses, 258 cell-type specific differentially-methylated positions were identified from the 450K BeadChip and 125 differentially-methylated regions from bisulfite sequencing. DNA methylation was also shown to be stable, as similar methylation differences found in the preliminary study, were again detected in the same twin pairs sampled years later. As DNA methylation is a stable marker, it could be used as a biomarker. β-cell death in diabetes releases DNA with unmethylated CpG sites in the insulin promoter region into the blood circulation. To detect these differences, an assay was also developed testing serum samples from monozygotic twin pairs. The data presented provided comprehensive DNA methylation profiles in type 1 diabetes from this discovery cohort. The methylation signature found will then be validated in diabetic, pre-diabetic and control singletons. This in turn will provide data for later functional analyses to identify genes associated with type 1 diabetes risk.

Chronic conditions and their management have become a major global public health problem which poses a serious challenge for both health care systems and affected individuals. Type 2 diabetes is one such condition affecting almost 200 million people around the world, a number that is expected to double by 2020. As with most chronic conditions its management requires significant and permanent changes in people???s daily life practices as well as a strict medication regimen. Recent research demonstrates that it is possible to control the complications of diabetes, and even to prevent its development in predisposed individuals by following recommended treatments. Yet studies show that only 2% of people living with diabetes heed their treating team???s advice. This signals a serious discordance between scientifically generated information and its place in the daily lives of people living with diabetes. This study sought to discover how to change the factors that prevent people with type 2 diabetes from following their recommended treatments. Firstly a participant observation process in four diabetes education centres was used to define the characteristics of the context in which people with diabetes and their treating teams interacted. This was followed by a nine-month participatory action process in two of the four centres in which participants defined the problematic areas in the management of their diabetes and devised plans to tackle these problems. They then attempted to implement these plans while exploring how and why their plans did or did not work. The findings indicate that the decision to follow recommended treatments is far from being a matter of individual choice. Rather it is heavily influenced by a complex interaction of numerous factors that people with diabetes have limited power to change. This study reveals that the management of chronic conditions such as diabetes could be enhanced where operational and practical knowledge about the condition is provided to people living with the disorder by health care providers responsive to patients??? perspectives, and where patients, providers and policy-makers recognise that health is a resource constructed in the wider social context, whose every element needs to be harnessed in encouraging people to make healthier life decisions.

Thesis (M.S.)--Florida State University, 2004. / Advisor: Dr. Deborah Frank, Florida State University, School of Nursing. Title and description from dissertation home page (viewed 6/16/04). Includes bibliographical references.

Dissertation (Ph.D.) - Simon Fraser University, 2005. / Dissertation (School of Kinesiology) / Simon Fraser University. Includes bibliographical references.

Thesis (M.P.H.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 43-47).

Thesis (M.P.H.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 44-46).

Thesis (M.P.H.)--University of Queensland, 2002. / Includes bibliographical references.

No description available.

No description available.