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Marjan Tabesh Understanding the Relationship between Obesity/ Fat distribution/Metabolic Profiles and Vitamin D Status in Young Women (The Safe-D study) Marjan Tabesh Supervisors Professor John D. Wark Professor Suzanne M. Garland Associate Professor Alison Nankervis Mrs Alexandra Gorelik Submitted in total fulfilment of the requirements of the degree of Doctor of Philosophy March 2018 The University of Melbourne, Faculty of Medicine, Dentistry and Health Sciences, Department of Medicine Royal Melbourne hospital i Table of Contents ABSTRACT ............................................................................................................................... 1 PREFACE AND ACKNOWLEDGEMENTS ........................................................................... 3 DECLARATION ....................................................................................................................... 4 CONTRIBUTION...................................................................................................................... 5 THESIS LAYOUT..................................................................................................................... 7 ABBREVIATIONS ................................................................................................................... 9 PUBLICATIONS AND PRESENTATIONS .......................................................................... 12 GENERAL AIM ...................................................................................................................... 14 Chapter 1 .................................................................................................................................. 15 INTRODUCTION AND LITERATURE REVIEW ............................................................... 15 1.1 Introduction .................................................................................................................... 16 1.1.1 Cardiovascular disease ............................................................................................ 16 1.1.2 Obesity ..................................................................................................................... 17 1.1.3 Body composition .................................................................................................... 19 1.1.4 Diabetes ................................................................................................................... 20 1.1.5 Vitamin D ................................................................................................................ 22 1.1.6 Vitamin D, calcium and parathyroid hormone ........................................................ 26 1.1.7 Mobile health technologies and health outcomes .................................................... 26 1.2 Mechanisms of association of vitamin D and CVD risk factors .................................... 28 1.2.1 Mechanisms of association of vitamin D and lipid profiles .................................... 28 1.2.2 Mechanisms of association of vitamin D and blood pressure ................................. 29 1.2.3 Mechanisms of vitamin D and potential direct effects on atherosclerosis .............. 29 1.2.4 Mechanisms of association between vitamin D and obesity ................................... 30 1.2.5 Mechanisms of association of vitamin D and body composition and fat distribution .......................................................................................................................................... 31 1.2.6 Mechanisms of association of vitamin D and diabetes............................................ 32 1.3 Literature review ............................................................................................................ 33 1.3.1 Vitamin D and obesity ............................................................................................. 35 1.3.2 Vitamin D and body composition/fat distribution ................................................... 42 1.3.3 Vitamin D and vascular health ................................................................................ 44 1.3.4 Vitamin D and inflammation ................................................................................... 46 1.3.5 Vitamin D and lipid profiles .................................................................................... 47 1.3.6 Vitamin D and blood pressure ................................................................................. 50 ii 1.3.7 Vitamin D and diabetes mellitus ............................................................................. 53 1.3.8 Vitamin D deficiency and pregnancy ...................................................................... 57 1.3.9 Effects of behavioural intervention by using mobile health (m-health) on health outcomes ........................................................................................................................... 58 1.4 Importance of the study .................................................................................................. 59 1.5 Rationale......................................................................................................................... 60 1.6 Aims ............................................................................................................................... 62 1.7 Methodological approach and theoretical framework .................................................... 63 Chapter 2 .................................................................................................................................. 65 MATERIALS AND METHODS ............................................................................................. 65 2.1 Study design ................................................................................................................... 66 2.2 Subject selection ............................................................................................................. 67 2.2.1 Inclusion criteria ...................................................................................................... 67 2.2.2 Exclusion criteria ..................................................................................................... 68 2.3 Proposed sample size ..................................................................................................... 70 2.4 Recruitment .................................................................................................................... 71 2.5 Verbal, written and electronic consent ........................................................................... 75 2.6 Trial interventions .......................................................................................................... 76 2.6.1 Behavioural intervention group ............................................................................... 76 2.6.2 Pharmacological intervention group ........................................................................ 77 2.6.3 Control group ........................................................................................................... 77 2.7 Randomisation ................................................................................................................ 78 2.8 Blinding .......................................................................................................................... 78 2.9 Data collection................................................................................................................ 79 2.9.1 Questionnaire data ................................................................................................... 84 2.9.2 Site visit assessment and rationale........................................................................... 86 2.9.3 Blood collection ....................................................................................................... 87 2.9.4 Physical examination ............................................................................................... 91 2.9.5 Skin reflectance ....................................................................................................... 93 2.9.6 Pregnancy test .......................................................................................................... 93 2.9.7 Bone density and body composition scans .............................................................. 93 2.9.8 Sun exposure/SunSmart behaviour .......................................................................... 94 2.9.9 Calculated variables ................................................................................................. 96 2.10 Young Female Health Initiative (YFHI) study ............................................................ 98 iii 2.11 Confounding ................................................................................................................. 98 2.12 Statistical analysis ........................................................................................................ 99 2.13 Data handling ............................................................................................................. 101 2.14 Compliance................................................................................................................. 101 2.15 Withdrawal ................................................................................................................. 102 2.16 Ethics and legal consideration .................................................................................... 103 2.17 Clinically-significant
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