Medicine (Northwest Academic Centre) - Theses
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ItemSun exposure and type 2 diabetes mellitus: Can sun exposure lower type 2 diabetes risk?( 2015)Background: Lower serum 25-hydroxyvitamin D (25OHD) levels have been consistently associated with increased type 2 diabetes mellitus (T2DM) prevalence and incidence in systematic reviews and meta-analyses of observational studies, however this association has not consistently been replicated in vitamin D supplementation trials. This disparity may be due to a number of different factors: lack of power in the trials due to small sample size, insufficient duration of dosing, baseline vitamin D or glycaemic status differing between studies, low supplementation compliance or insufficient vitamin D dose. Alternatively, lower 25OHD levels may be a product, rather than a cause of ill-health, or they may share pathology earlier in life or in disease progression so that supplementing with vitamin D in adulthood has no effect on disease outcome. This body of work presents another explanation: given that sun exposure is the most influential contributor to serum 25OHD levels, observational studies may be reporting an effect of sun exposure, rather than vitamin D, on T2DM. Therefore vitamin D supplementation trials may be failing to capture any additional benefits of sun exposure through non-vitamin D pathways. The aim of this body of work was to investigate the possible association between sun exposure and T2DM endpoints reported in scientific literature as well as in an original analysis. A major objective of the original analysis was to determine whether or not any association found between sun exposure and T2DM incidence was through non-vitamin D pathways. Methods: Following a literature review, a systematic review of observational studies reporting on associations between sun exposure variables and T2DM-related endpoints was conducted. The potential of an association between sun exposure- measured using ambient ultraviolet radiation (UVR), and five-year cumulative incidence of T2DM was explored using a prospective, national diabetes cohort (AusDiab). A causal mediation analysis was undertaken to explore whether or not there were effects of ambient UVR on cumulative T2DM incidence, via non-vitamin D pathways. Results: The systematic review revealed that high-level evidence for an association between sun exposure and T2DM-related outcomes was lacking. There was moderate-level evidence for greater sun exposure reducing T2DM incidence. The opposite was found in the original analysis using the AusDiab cohort: ambient UVR was associated with increased T2DM incidence (OR=1.17, 95% CI: 1.01-1.36, p=0.04). This association was independent of an effect of age, sex, body mass index, physical activity, ethnicity, smoking status and serum 25OHD levels, but was likely to be confounded by area-level determinants of health due to the nature of the exposure variable. The major limitations of this work were that the sun exposure measures were suboptimal. Time-of-year measures were the most common sun exposure variables contained in the systematic review, and ambient UVR at the site of participant recruitment was the proxy for sun exposure in the original analysis. Conclusion: There is likely to be a complex relationship between sun exposure and T2DM. The direction of the association between sun exposure and T2DM incidence, as well as delineation of the mechanistic pathways through which this association may exist, are yet to be confirmed. Future studies are encouraged to use person-level sun exposure measurements, and findings from such studies may influence sun protection policy.
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ItemNovel approaches to an improved understanding of the epidemiology and control of hepatitis B virus infection in Australia( 2009)Background: The most recent estimate for the number of Australians living with chronic hepatitis B virus (HBV) infection is 150,000, with over one million ever having been infected. One in four people with chronic infection will die as a result. Worldwide, the burden of chronic HBV infection is great. As many as 400 million people are chronically infected, and the World Health Organisation estimates that as a result HBV infection is the tenth leading cause of death. Aim: The aim of the research presented in this thesis is to improve the accuracy and relevance of our understanding of the epidemiology and control of HBV infection in Australia, through the development of new methodological approaches to the collection and analysis of relevant epidemiological data. Methods: Three novel approaches were adopted. First, a serosurvey of a randomised, age-structured convenience sample of over 3200 specimens was performed spanning the period from 1995 to 2005 to estimate the prevalence of markers of infection with, and immunity to HBV. Secondly, a comparative analysis of the serosurvey results with national surveillance notifications since 1971 and migration records since 1945 was undertaken. Finally, a complex deterministic mathematical model of HBV infection in Australia was constructed simulating the entire population between 1951 and 2050. Results: The serosurvey indicates that chronic infection with HBV is more common in the Victorian population than existing national serosurvey estimates suggest, and the coverage of immunisation programs (particularly of adolescents) is far from universal. Significant geographic, age, and gender disparities in the prevalence of chronic HBV infection were identified in the serosurvey, which appear in part to relate to historical migration patterns and which could be used to develop a targeted and effective public health response. The comparative analysis of the serosurvey results with notifications and migration data demonstrates coherence of these disparate sources of information, and suggest that knowledge of migration patterns can lead to robust predictions of future notifications. The novel regression model developed implies that at least 50,000 people with chronic HBV infection are undiagnosed. The mathematical model of HBV infection in the Australian population is unique in many respects, and has been validated against external data to provide reassurance regarding the accuracy of the simulated outcomes. Some of these outcomes include an estimated 160,000 Australians living with chronic HBV infection in 2009, increasing by several thousand people every year, and that less than 5 per cent of chronic infections entering the population are able to be addressed by domestic vaccination or other prevention programs. Conclusion: The new insights into the epidemiology of HBV infection in Australia provided by the approaches described all suggest a large and increasing burden of chronic HBV infection. New approaches are needed to provide essential policy outcomes to assist and empower Australians living with chronic HBV infection. If this does not occur, the economic and human costs to our community are likely to become great.