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Effect of Total Body Iron on Metabolic Dysfunction Among U.S. Females in the Nhanes 2003-2010, Aged 12-49

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Effect of Total Body Iron on Metabolic Dysfunction Among U.S. Females in the Nhanes 2003-2010, Aged 12-49 University of Louisville ThinkIR: The University of Louisville's Institutional Repository Electronic Theses and Dissertations 12-2017 Effect of total body iron on metabolic dysfunction among U.S. females in the Nhanes 2003-2010, aged 12-49. Joseph Michael Carhart University of Louisville Follow this and additional works at: https://ir.library.louisville.edu/etd Part of the Epidemiology Commons Recommended Citation Carhart, Joseph Michael, "Effect of total body iron on metabolic dysfunction among U.S. females in the Nhanes 2003-2010, aged 12-49." (2017). Electronic Theses and Dissertations. Paper 2827. https://doi.org/10.18297/etd/2827 This Doctoral Dissertation is brought to you for free and open access by ThinkIR: The University of Louisville's Institutional Repository. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of ThinkIR: The University of Louisville's Institutional Repository. This title appears here courtesy of the author, who has retained all other copyrights. For more information, please contact [email protected]. EFFECT OF TOTAL BODY IRON ON METABOLIC DYSFUNCTION AMONG U.S. FEMALES IN THE NHANES 2003-2010 SURVEY, AGED 12-49 By Joseph Michael Carhart MA, University of Louisville, 2010 BS, Morehead State University, 2000 A Dissertation Submitted to the Faculty of the School of Public Health and Information Sciences of the University of Louisville in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Public Health Science Department of Epidemiology and Population Health University of Louisville Louisville, Kentucky December 2017 EFFECT OF TOTAL BODY IRON ON METABOLIC DYSFUNCTION AMONG U.S. FEMALES IN THE NHANES 2003-2010 SURVEY, AGED 12-49 By Joseph Michael Carhart MA, University of Louisville, 2010 BS, Morehead State University, 2000 A Dissertation Approved on December 05, 2017 by the following Dissertation Committee: Dr. Frank D. Groves Dr. Kathy B. Baumgartner Dr. Richard N. Baumgartner Dr. Shesh N. Rai Dr. Stephen J. Winters ii DEDICATION This Dissertation is dedication to my parents Mrs. Maguana Carhart-Qualls and Mr. Michael Qualls who have provided me with invaluable support and educational opportunities. iii ACKNOWLEDGMENTS I would like to thank my advisor and dissertation director, Dr. Frank Groves, for his guidance, patience and humor during our research. I would also like to thank the other committee members for their guidance and commentary over the past 6 years. Moreover, I would like to express my thanks and gratitude to my wife, Andrea, for her patience and understanding during those times when I would say “Just a little bit longer. I can see the light at the end of the tunnel” and yet it seemed quite often that no end was in sight. This entire process has thus been a team-effort and I am happy to say that we have finally made it. iv ABSTRACT EFFECT OF TOTAL BODY IRON ON METABOLIC DYSFUNCTION AMONG U.S. FEMALES IN THE NHANES 2003-2010 SURVEY, AGED 12-49 Joseph M. Carhart December 05, 2017 Experimental and epidemiological studies have reported positive associations between iron parameters and metabolic dysfunction including: Type 2 diabetes mellitus (T2DM) (1-6), metabolic syndrome (7-15), non-alcoholic fatty liver disease (NAFLD) (16-22) and insulin resistance (23,24) with a number of studies showing that reductions in total body iron via dietary modification (e.g., reducing red meat intake) or phlebotomy lead to increases in insulin sensitivity (25), decreases in insulin resistance (26), and reductions in the prevalence of complications associated with T2DM (5, 27), metabolic syndrome (28) and NAFLD (22, 29). Moreover, the risk associated with these outcomes and total body iron differ between males and females and it has been hypothesized that the divergence in risk of disease due to total body iron is related to the female reproductive lifespan (e.g., age at menarche, parity, oral contraceptive use and age at menopause). Regardless of study design, serum ferritin and transferrin saturation have consistently been used in these investigations to estimate total iron stores, which are affected by inflammation and demonstrate diurnal variation. v The aim of the current study was to examine the clinical utility of an index of iron repletion developed by JD Cook et al. in 1993 (i.e. FeCOOK), which is unaltered by inflammation or liver function in a nationally-representative, community-dwelling, non- institutionalized group of females participating in continuous NHANES from 2003 to 2010 and to examine the association between the index and metabolic dysfunction. The current results highlight the clinical utility of FeCOOK in assessing the iron status in females of reproductive age. I did not observe a statistically significant association between metabolic dysfunction and continuously-scaled FeCOOK. However, when FeCOOK was modeled in accordance with common reporting patterns (i.e., categorically), significant, positive associations between increasing FeCOOK and metabolic dysfunction were observed among all females, and this pattern persisted after stratification by ethnicity and menopausal status. Further research is warranted to examine the clinical utility of FeCOOK among other cohorts. Moreover, additional research using FeCOOK is recommended in order to replicate these findings among a larger sample comprised of both males and older females. vi TABLE OF CONTENTS ACKNOWLEDGMENTS…………………………………………………..……………iv ABSTRACT……………………………………………………………….………………v LIST OF TABLES…………………………………………………………….…...…….xx LIST OF FIGURES ........................................................................................................ xxii CHAPTER 1: INTRODUCTION ........................................................................................1 Aim 1 ...........................................................................................................................3 Aim 2 ...........................................................................................................................3 Hypothesis 2A.1 ...............................................................................................3 Hypothesis 2A.2 ...............................................................................................3 Hypothesis 2A.3 ...............................................................................................3 Hypothesis 2A.4 ...............................................................................................3 Hypothesis 2A.5 ...............................................................................................3 Hypothesis 2B.1 ...............................................................................................4 Hypothesis 2B.2 ...............................................................................................4 Hypothesis 2B.3 ...............................................................................................4 Aim 3 ...........................................................................................................................4 Aim 4 ...........................................................................................................................4 Hypothesis 4A.1 ...............................................................................................5 Hypothesis 4A.2 ...............................................................................................5 vii Hypothesis 4A.3 ...............................................................................................5 Hypothesis 4A.4 ...............................................................................................5 CHAPTER 2: OVERVIEW OF IRON METABOLISM AND IRON STATUS IN HUMAN POPULATIONS ......................................................................................6 Systemic iron metabolism .............................................................................................6 Cellular iron metabolism..............................................................................................11 Iron status in human populations .................................................................................12 CHAPTER 3: IRON IN HUMAN HEALTH AND DISEASE .........................................23 Iron in human health ....................................................................................................23 Functional dependencies on iron .....................................................................23 Iron in human disease ..................................................................................................28 Iron in infectious disease .............................................................................................28 Iron in chronic disease .................................................................................................31 Iron and cardiovascular disease .......................................................................33 Iron and cancer .................................................................................................37 Iron and cerebrovascular disease .....................................................................40 Iron and chronic obstructive pulmonary disease .............................................41 Iron and Alzheimer's disease ...........................................................................42 CHAPTER 4: LITERATURE REVIEW: IRON AND METABOLIC DYSFUNCTION Iron and Type 2 diabetes mellitus ................................................................................44
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