[Relationship between Resistin Hormone, Metabolic Parameters, Body Mass Index and Resistin Polymorphism Gene in persons with Type 2 Diabetes Mellitus]

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ACKNOWLEDGEMENT

I would take this opportunity to thank my research supervisor, family and friends for their support and guidance without which this research would not have been possible.

DECLARATION

I, [type your full first names and surname here], declare that the contents of this dissertation/thesis represent my own unaided work, and that the dissertation/thesis has not previously been submitted for academic examination towards any qualification. Furthermore, it represents my own opinions and not necessarily those of the University.

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ABSTRACT

Type 2 diabetes (T2D) is a complex metabolic disease characterized by elevated blood glucose levels in response to systemic insulin resistance. Over 23 million (10-13%) U.S. adults were estimated to be living with T2D, and approximately 1.6 million new cases are diagnosed each year. The estimated cost from medical expenditures and lost productivity in the U.S. totaled $174 billion in 2007—this is considered an underestimate as nearly one-third of all diabetes cases are presumably undiagnosed. Worldwide, the burden of disease is growing even more rapidly than in the U.S. As a whole, these data suggest that current prevention strategies fall short of staving off the rising numbers of T2D. Thus, new preventive and therapeutic strategies are needed. The major risk factors for T2D are well known (e.g., age, obesity). However, the biological framework through which these risk factors translate into biological dysfunction is poorly understood. Understanding the details of this framework can lead to newer, more targeted strategies for preventing the development of T2D. We then examined whether individuals who later developed T2D had higher levels of these markers at baseline. Second, for protein markers that have been implicated with the development of disease, one can employ a “candidate gene approach,” which is a targeted approach for examining the association between chromosomal regions of interest (e.g., the gene coding for a protein marker that has been associated with disease) and development of disease. Furthermore, available data on genotypes, plasma intermediate phenotypes, and disease outcome allow for estimation of the potential causal relation between plasma intermediate markers and disease risk through instrumental variable analysis following the principles of Mendelian randomization (i.e., the use of genetic variants as randomized instruments for estimating the potential unconfounded association between an intermediate phenotype and disease). Lastly, with the recent advances in genotyping technology, millions of single nucleotide polymorphisms (SNPs) spanning the genome can be examined simultaneously for their associations with T2D risk.

ABSTRACTIV

CHAPTER 1: INTRODUCTION8

Introduction8

Background9

Significance13

Problem Statement14

Thesis Statement15

Purpose of the Study15

Aims and Objectives15

Hypothesis15

Research Questions16

CHAPTER 2: LITERATURE REVIEW17

The Relationship between Diabetes and Obesity17

Obesity as the Indicator of Poor Socioeconomic Status21

Obesity as the Indicator of Poor Cognitive Functioning21

Obesity as the Indicator of Poor Academic Performance23

Treatment for Obesity24

Diabetes as the Indicator of Poor Socioeconomic Status25

Diabetes as the Indicator of Poor Cognitive Functioning27

Diabetes as the Indicator of Poor Academic Performance28

Diabetes and its Prevalence29

Complications of diabetes33

Managing Diabetes35

Biomarkers and their usefulness43

Heart failure management through biomarkers44

Latest biomarker discoveries45

CHAPTER 3: METHODOLOGY47

Research Design47

Study population47

Type 2 diabetes ascertainment50

Assays of Biological Markers50

Genotyping ...