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UNIVERSITY of CALIFORNIA, IRVINE Dietary Patterns and Cardiometabolic Disease Risk DISSERTATION Submitted in Partial Satisfactio UNIVERSITY OF CALIFORNIA, IRVINE Dietary Patterns and Cardiometabolic Disease Risk DISSERTATION submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Epidemiology by Kristin Michelle Hirahatake Dissertation Committee: Assistant Professor Andrew Odegaard, Chair Assistant Professor Luohua Jiang Adjunct Professor Nathan Wong 2018 © 2018 Kristin Hirahatake TABLE OF CONTENTS Page LIST OF FIGURES iv LIST OF TABLES v ACKNOWLEDGEMENTS vii CURRICULUM VITAE viii ABSTRACT ix INTRODUCTION 1 CHAPTER 1: The Natural History of Type 2 Diabetes 3 Normal Glucose Homeostasis 3 Pathogenesis of T2D 4 Epidemiology 9 Risk Factors 10 Diagnosis 13 Treatment 18 Prevention 22 Complications 24 CHAPTER 2: Dietary Patterns and Type 2 Diabetes Risk 26 Overview of Dietary Indices 29 Literature Review of Studies: Dietary Patterns and T2D Risk 32 Overview of Beverages and T2D Risk 36 Literature Review of Studies: Beverage Consumption and T2D Risk 38 CHAPTER 3: Type 2 Diabetes and Cardiovascular Disease 43 Natural History of Cardiovascular Disease 43 T2D and Cardiovascular Disease Risk 46 Dietary Patterns and Cardiovascular Disease Risk in T2D 51 CHAPTER 4: Populations Under Study 70 Coronary Artery Risk Development in Young Adults (CARDIA) 70 Women’s Health Initiative (WHI) 75 CHAPTER 5: Variations on Dietary Patterns and Risk of Incident Type 2 Diabetes 85 Mellitus in Young Adults: the CARDIA Study Introduction 86 Methods 87 Results 94 ii Discussion 98 Tables 104 CHAPTER 6: Artificially-sweetened and Sugar-sweetened Beverages and Risk of 119 Incident Type 2 Diabetes in Young Adults: the CARDIA Study Introduction 121 Methods 122 Results 128 Discussion 131 Tables 137 CHAPTER 7: Diet Quality and Cardiovascular Disease Risk in Postmenopausal 143 Women with Type 2 Diabetes: The Women’s Health Initiative Introduction 145 Methods 146 Results 153 Discussion 155 Tables 162 CHAPTER 8: Summary and Conclusions 176 REFERENCES 177 iii LIST OF FIGURES Page Figure 1.1 Normal Glucose Homeostasis 8 Figure 1.2 The Ominous Octet 8 Figure 3.1 Atherosclerosis Progression 45 iv LIST OF TABLES Page Table 1.1 Type 2 Diabetes Risk Factors 12 Table 1.2 Criteria for Type 2 Diabetes Diagnosis 15 Table 1.3 Categories of Prediabetes 17 Table 1.4 Type 2 Diabetes Medical Nutrition Therapy 20 Table 1.5 Glucose-lowering Medications for Type 2 Diabetes 21 Table 2.1 Cohort Studies of Dietary Patterns and Type 2 Diabetes 33 Table 2.2 Cohort Studies of Artificially Sweetened Beverages and Type 2 38 Diabetes Table 4.1 Women’s Health Initiative Inclusion and Exclusion Criteria 77 Table 4.2 Women’s Health Initiative Participant Baseline Characteristics 80 Table 5.1 Baseline Characteristics of CARDIA Participants by Cumulative 104 Average Dietary Pattern Score Table 5.2 Pearson’s Correlation Between Dietary Pattern Scores 108 Table 5.3 Association between Cumulative Average Dietary Patterns and 109 30-year Diabetes Risk in the CARDIA Study Table 5.1S Description of Dietary Pattern Scores 110 Table 5.2S Description of CARDIA A Priori Diet Quality Score 111 Table 5.3S Nutrient Characteristics by 2015 DGA Diet Score Quartile 115 Table 5.4S Nutrient Characteristics by Paleolithic Score Quartile 116 Table 5.5S Nutrient Characteristics by Low Carbohydrate Score Quartile 117 Table 5.6S Nutrient Characteristics by Empty Calorie Score Quartile 118 v Table 5.7S Association Between Year 20 Percent Empty Calories and T2D 118 Risk in the CARDIA Study Table 6.1 Baseline Characteristics of CARDIA Participants by Quintile 137 of Sweetened Beverage Intake Table 6.2 Association Between Cumulative Average Sweetened Beverage 139 Intake and T2D Risk in the CARDIA Study Table 6.3 Association Between Beverage Consumption Patterns Over 20 140 Years and T2D Risk in the CARDIA Study Table 6.1S Characteristics of CARDIA Participants According to Quintile 141 of Total Sweetened Beverage Consumption Table 6.2S Association of Frequency of Sweetened Beverage Consumption 142 and T2D Risk in the CARDIA Study Table 7.1 Baseline Characteristics of WHI Participants with Prevalent T2D 162 by Dietary Pattern Score Table 7.2 Pearson’s Correlation Between Dietary Pattern Scores 169 Table 7.3 Association Between Dietary Patterns and Incident CVD, Coronary 170 Heart Disease, and Stroke in Women with T2D in the WHI Table 7.1S Nutrient Characteristics by DASH Diet Score Quintile 172 Table 7.2S Nutrient Characteristics by Mediterranean Diet Score Quintile 173 Table 7.3S Nutrient Characteristics by ADA Diet Score Quintile 174 Table 7.4S Nutrient Characteristics by Paleolithic Diet Score Quintile 175 vi ACKNOWLEDGEMENTS I would like to express my most sincere appreciation to my committee chair, Professor Andrew Odegaard, for his mentorship throughout my time as a graduate student. He continually challenged and encouraged me as I worked to master epidemiologic methods and refine my research and analytical skills. I am grateful for his willingness to help me pursue my goals and for his continued support along this journey. I would also like to thank my other dissertation committee members, Professors Luohua Jiang and Nathan Wong, for their guidance and helpful commentary on my manuscripts. Lastly, I could not have completed this dissertation and graduate program without the ongoing support of my loving husband, Chris, and my wonderful family and friends. vii CURRICULUM VITAE Kristin Michelle Hirahatake 2008 B.S. Human Biology, University of California, San Diego 2010-2011 Teaching Assistant, University of California, Davis 2011 M.S. Nutritional Biology, University of California, Davis 2011-2012 Dietetic Internship, Veteran’s Affairs San Diego Healthcare System, La Jolla 2016-2017 Teaching Assistant, University of California, Irvine 2018 PhD Epidemiology, University of California, Irvine FIELD OF STUDY Dietary Patterns and Cardiometabolic Disease Risk PUBLICATIONS Meissen, J. K., Hirahatake, K. M., Adams, S. H., & Fiehn, O. (2015). Temporal metabolomic responses of cultured HepG2 liver cells to high fructose and high glucose exposures. Metabolomics, 11(3), 707-721. Hirahatake, K. M., Slavin, J. L., Maki, K. C., & Adams, S. H. (2014). Associations between dairy foods, diabetes, and metabolic health: potential mechanisms and future directions. Metabolism, 63(5), 618-627. Hirahatake, K.M., Meissen, J.K., Feihn, O., Adams, S.H. Comparative Effects of Fructose and Glucose on Lipogenic Gene Expression and Intermediary Metabolism in HepG2 Liver Cells. PLoS ONE 6 (11): e26583.doi:10.1371/journal.pone.0026583. viii ABSTRACT OF THE DISSERTATION Dietary Patterns and Cardiometabolic Disease Risk By Kristin Michelle Hirahatake Doctor of Philosophy in Epidemiology University of California, Irvine, 2018 Assistant Professor Andrew Odegaard, Chair Diet was recently identified as the largest contributing risk factor across the leading causes of death in the United States. The nature of the diet-disease relationship based on the current body of evidence, however, remains inconclusive. The objective of this dissertation is to further explore the diet-disease relationship, specifically focusing on type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD). This dissertation consists of three separate research projects aiming to investigate the association between 1) contemporary national dietary guidelines and popular adapted dietary trends and 2) sweetened beverage consumption and T2D risk in young adults and 3) diet quality and CVD risk in postmenopausal women with prevalent T2D. In the first and second projects, prospective analyses of 4,627 young adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study with repeated dietary histories were conducted. The first project examined the association between a priori dietary pattern scores created to reflect the 2015 Dietary Guidelines for Americans Scientific Report, a modern-day Paleolithic diet, low carbohydrate diet, CARDIA A Priori Diet Quality Score and diet high in overall consumption of empty calories and T2D risk in young adults over time. The second project examined the association between artificially-sweetened beverage, sugar-sweetened beverage, and total sweetened beverage consumption and T2D risk in young adults in the CARDIA cohort. For the ix third project, a prospective analysis of 5,809 postmenopausal women with prevalent T2D from the Women’s Health Initiative was performed to study the relationship between diet quality as measured by four dietary pattern scores, an alternate Mediterranean (aMed), Dietary Approaches to Stop Hypertension (DASH), Paleolithic, and the American Diabetes Association (ADA) recommendations, and CVD risk over time. Multivariable Cox proportional hazards regression was used to characterize the prospective associations with incident T2D for the first two projects and incident CVD for the third project. Dietary pattern scores reflecting contemporary recommendations and popular patterns were not associated with T2D risk while the A Priori Diet Quality score, which largely aligns with the 2015 DGA, was strongly inversely associated with lower 30-year T2D risk in the CARDIA cohort. Additionally, long-term total-sweetened beverage consumption was associated with an increased risk of T2D, independent of diet quality, lifestyle factors, and BMI in this population; suggesting that whether or not they are causally related to T2D, higher intake of these beverages serves as a strong predictor of higher T2D risk in young adults. The aMed, DASH and ADA dietary patterns, emphasizing fruits, vegetables, whole grains, nuts/seeds,
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