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Oral Glucose Insulin Secretion Test for Identifying Patients with Insulin Resistance David Kershner Walden University

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Oral Glucose Insulin Secretion Test for Identifying Patients with Insulin Resistance David Kershner Walden University Walden University ScholarWorks Walden Dissertations and Doctoral Studies Walden Dissertations and Doctoral Studies Collection 2018 Oral Glucose Insulin Secretion Test for Identifying Patients with Insulin Resistance David Kershner Walden University Follow this and additional works at: https://scholarworks.waldenu.edu/dissertations Part of the Endocrinology Commons, Endocrinology, Diabetes, and Metabolism Commons, and the Epidemiology Commons This Dissertation is brought to you for free and open access by the Walden Dissertations and Doctoral Studies Collection at ScholarWorks. It has been accepted for inclusion in Walden Dissertations and Doctoral Studies by an authorized administrator of ScholarWorks. For more information, please contact [email protected]. Walden University College of Health Sciences This is to certify that the doctoral dissertation by David Kershner has been found to be complete and satisfactory in all respects, and that any and all revisions required by the review committee have been made. Review Committee Dr. Vasileios Margaritis, Committee Chairperson, Public Health Faculty Dr. Jeff Snodgrass, Committee Member, Public Health Faculty Dr. Simone Wilson Salandy, University Reviewer, Public Health Faculty Chief Academic Officer Eric Riedel, Ph.D. Walden University 2018 Abstract Oral Glucose Insulin Secretion Test for Identifying Patients with Insulin Resistance by David Kershner MSPA, MD Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Public Health Walden University August 2018 Abstract Insulin resistance is an increasing public health issue with the current literature, suggesting reduced sensitivity of insulin leads to adult onset diabetes and associated downstream pathologies that reduce life expectancy. The main objectives of this study were to evaluate the ability of the Oral Glucose Insulin Secretion Test (OGIST) to identify insulin resistance and examine differences in the insulin sensitivity based on gender, age, and ethnicity. This study was supported by the insulin resistance theory which focuses on the reduced ability of insulin to bind to the cellular insulin receptor, reducing the sensitivity of insulin. The OGIST lab results of a total of 250 patients, aged 18–65, were included in this study from a major city in the midwestern United States. Binomial logistic regression was used to evaluate the relationship between the dependent variables and the validation independent variables and analyze the possible differences seen in insulin, proinsulin, C-peptide, and HbA1c with age. The OGIST demonstrated the ability to identify elevated levels of insulin, proinsulin, and C-peptide at the end of the first phase insulin secretion to glucose. The results of this study demonstrated patients with insulin resistance exhibited a greater reduction in insulin production with age compared to those without insulin resistance. There were no changes observed between gender or ethnicity. The OGIST was the only test that demonstrated the ability to identify the individual’s insulin sensitivity, β-cell function, and progression to diabetes. The ability of the OGIST to identify both insulin resistance and β-cell function can contribute to positive social change by encouraging further research for the early diagnosis and treatment of insulin resistance and the reduction in adult onset diabetes. Oral Glucose Insulin Secretion Test for Identifying Patients with Insulin Resistance by David Kershner MSPA, MD Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Public Health Walden University August 2018 Acknowledgments I would like to thank my committee for helping me through this process and their insight. I would like to thank Jeffery Snodgrass for being part of my committee and for his help. Susan Nyanzi, PhD, for her encouragement and help. I would like to thank Dr. Vasileios Margaritis for volunteering to be my committee chair at the end of my dissertation. Without his guidance, insight, and help I would not have been able to finish. I would like to thank my beautiful wife, Renee, for her encouragement and patience while I spent many days and nights working on this project. Table of Contents List of Tables .......................................................................................................................v List of Figures ................................................................................................................... vii Chapter 1: Introduction to the Study ....................................................................................1 Background ....................................................................................................................1 Problem Statement .........................................................................................................4 Purpose of the Study ......................................................................................................5 Research Questions ........................................................................................................6 Framework .....................................................................................................................7 Nature of the Study ........................................................................................................8 Definitions......................................................................................................................9 Assumptions .................................................................................................................10 Limitations ...................................................................................................................11 Significance..................................................................................................................12 Summary ......................................................................................................................14 Chapter 2: Literature Review .............................................................................................16 Introduction ..................................................................................................................16 Literature Search Strategy............................................................................................17 Epidemiology of Insulin Resistance ............................................................................18 Insulin Resistance Theory ............................................................................................22 Insulin Resistance ........................................................................................................23 Insulin Resistance Syndrome .......................................................................................24 i Metabolic Syndrome ....................................................................................................24 Current Direct Tests for Insulin Resistance .................................................................25 Oral Glucose Tolerance Test (OGTT) .................................................................. 25 Insulin Tolerance Test (ITT) ................................................................................. 26 Insulin Suppression Test (IST) ............................................................................. 27 The Frequently Sampled Intravenous Glucose Tolerance Test With Minimal Model Analysis (FSIGTT) ......................................................... 28 Glucose Clamp Test (GCT) .................................................................................. 28 Euglycemic-Hyperinsulinemic Clamp Test .......................................................... 29 Peripheral Insulin Sensitivity Index (ISI) ............................................................. 30 Hyperglycemic Clamp .......................................................................................... 30 Surrogate Indexes for Insulin Sensitivity/Resistance ..................................................31 Challenges With the Current Tests for Insulin Resistance ..........................................31 Cost-Effectiveness of Treating Insulin Resistance ......................................................32 Summary and Conclusions ..........................................................................................34 Chapter 3: Research Method ..............................................................................................35 Study Methods .............................................................................................................35 Research Questions and Hypotheses ...........................................................................36 Study Population ..........................................................................................................36 Measurements and Instrumentation .............................................................................37 Proinsulin .............................................................................................................. 39 Insulin ................................................................................................................... 40 ii C-Peptide............................................................................................................... 40 Glycated Hemoglobin (HbA1c) ...........................................................................
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