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Semi-Targeted Exposome Strategies to Measure Biomarkers of Exposure and Disease Associated with Type II Diabetes in Asian Indians


The prevalence of type II diabetes (T2D) is escalating worldwide, yet incidence rates differ dramatically between ethnic groups. Some known risk factors of T2D include diet, exercise, and genetic inheritability, yet these factors alone cannot fully explain the differences observed between populations. Better approaches are needed to identify other non-genetic factors, such as toxic chemical exposures, that are related to T2D, particularly in highly-susceptible populations. The exposome is a relatively new concept used to investigate causes of disease due to endogenous and exogenous exposures. This dissertation aims to use semi-targeted exposomics to examine biomarkers of exposure and disease that are associated with T2D. Chapter 1, the introduction, discusses the broader objectives of exposomics, including ideal comparison populations for identifying underlying causes of chronic disease. In the case of T2D, Asian Indians are a population of great interest, with a 3-4-fold higher risk of T2D than European white counterparts. Chapter 2 examines blood concentrations of environmental pollutants in small volumes of plasma in Asian Indian immigrants and a low-risk comparison group, European whites. This study is the first to investigate associations between persistent organic pollutants and T2D in Asian Indians. Chapter 3 describes a method to measure sources of variability in a potential biomarker of T2D, microRNA (miRNA). This study demonstrates the importance of empirically measuring technical and biological sources of variability and using simulations to inform power calculations for new biomarkers of interest. Chapter 4 takes lessons learned from Chapter 3 and applies them to a case-control study on plasma miRNA in Asian Indians. In the concluding Chapter 5, the current state of research on T2D as it relates to blood biomarkers of environmental exposures and disease are described for Asian Indians and other highly susceptible groups.

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