Behavioral and Pharmacoepidemiological Risk Factors and Mediators for Type Ii Diabetes Mellitus
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BEHAVIORAL AND PHARMACOEPIDEMIOLOGICAL RISK FACTORS AND MEDIATORS FOR TYPE II DIABETES MELLITUS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Victoria A. Zigmont, BS, MPH Graduate Program in Public Health The Ohio State University 2015 Dissertation Committee: Susan Olivo-Marston, PhD, MPH, Advisor Stephen Clinton, MD, PhD Randall Harris, MD, PhD Gail Kaye, PhD, RD, LD, PLCC Abigail Shoben, PhD Copyright by Victoria A. Zigmont 2015 ABSTRACT BACKGROUND: Type II diabetes mellitus (T2DM) is a serious and relevant public health problem. Lifestyle programs like the Diabetes Prevention Program (DPP) can delay a patient’s progression to T2DM. Identifying which patients are likely to enroll in these programs and tailoring recruitment approaches to those with perceived barriers is one way to increase engagement in health promotion. Previous literature on antidepressant use and T2DM has raised concerns that antidepressant use is associated with T2DM, however these studies have been variable in quality. Similarly, while statins are one of the most widely prescribed medications in the United States; concern has been raised that they are associated with incident T2DM. The effect of statin use on glycemic control in nondiabetic patients is currently unclear. METHODS: Three retrospective cohort studies were conducted among individuals in the Midwest enrolled in an insurance plan from 2011 through 2014. These studies combined data from medical and pharmacy claims, annual biometric screenings and a health survey. The goal of the first study was to identify differences between prediabetic patients who did and did not volunteer to enroll in a worksite DPP. Covariates were compared for prediabetics who did and did not elect to participate in the DPP using multivariable logistic regression (n=2,158). Generalized linear mixed models with random intercepts were then used to compare biometric trajectories for the two groups. The goal of studies two and three was to identify if antidepressant or statin users who were members of this ii insurance cohort were at risk for elevated HbA1c or T2DM development. The second study was restricted to patients with indications for antidepressant use (n=2,063) and the third study was among patients with indications for statin use (n=7,064). The methods were identical for studies two and three. Elevated glycosylated hemoglobin A1c (HbA1c) was compared for nondiabetic antidepressant, or statin, users and nonusers after applying inverse probability weighting with logistic regression for the outcome of elevated HbA1c (>6.0). To evaluate the risk of T2DM development, Cox proportional hazard models with time varying antidepressant, or statin, use compared incident T2DM diagnoses among antidepressant or statin users and nonusers. Comparisons were also made by duration of use and class for antidepressant, or statin, users and nonusers and intensity of dose was compared for statin users. RESULTS: The first analysis identified that prediabetics were more likely to express interest in the DPP if they were female, African American, older, free of hypertension, had more doctor visits, or lower self-efficacy to make healthy lifestyle changes. The second analysis found no differences in elevated HbA1c, or new onset T2DM, across antidepressant users, or duration of use. The third analysis found no differences in elevated HbA1c, however new onset of T2DM was highest among statin users who had been taking statins for 2 years or longer; no differences were observed by statin class. CONCLUSION: Current recruitment strategies are reaching individuals who are not representative of the greater prediabetic population. Targeted recruitment efforts for underrepresented groups are currently underway. A higher prevalence of elevated HbA1c was not observed among nondiabetic users of antidepressants or statins after controlling for baseline differences across groups. Additionally these findings indicate that the iii elevated T2DM risk among statin users may be isolated to a group of patients with higher T2DM risk, and for antidepressant users, an elevated risk of T2DM was not observed. iv DEDICATION To my loving husband Jason who has been endlessly supportive of my love for research and data. Thank you for being awesome and sticking by me. To my parents David and Elizabeth, and brother, Alex, for their support of my academic endeavors and for reminding me when it’s time to get back on track. v ACKNOWLEDGEMENTS There are many people who have helped me in the past years on this journey to getting my PhD. Thank you to the faculty at the Ohio State University College of Public Health; you have been instrumental in sculpting me into the researcher that I am today. Thank you to my advisor Dr. Susan Olivo-Marston, for her continued guidance, encouragement, mentorship and patience throughout this dissertation. Thank you for the academic freedom you have given me throughout this process. To my Committee: Dr. Abigail Shoben, Dr. Randall Harris, Dr. Gail Kaye, and Dr. Steven Clinton, thank you for your time, expertise, guidance and thoughtful feedback throughout this journey. Thank you to Dr. Judy Schwartzbaum for being a wonderful sounding board to brainstorm methodology questions and to Dr. Bo Lu for sharing your causal inference expertise with me. Thank you to Dr. Richard Snow for mentorship and guidance, and for allowing me to apply these projects to practice and to improving patient care. Thank you to my good friend Allahna Esber and my colleagues at OhioHealth who have been there for a much needed coffee break. To my mentors, Dr. Sandra Bulmer, and Dr. Jeffrey Shannon whose guidance and skilled teaching encouraged me to pursue a PhD. vi VITA 2003 – 2007 ................................................... B.S. Chemistry and Physiology & Neurobiology, University of Connecticut 2008 ............................................................... Organic Chemist, Pfizer Inc. Central Nervous System Chemistry, Groton, CT 2008 – 2009 ................................................... High School Science Teacher, Westhill High School, Stamford, CT 2009 – 2010 ................................................... Research Assistant Volunteer, Hepatic Insulin Resistance in Type II Diabetes, VA Hospital, West Haven, CT 2010 – 2011 ................................................... Graduate Assistant Coordinator, EHTP Department of Public Health, Southern Connecticut State University 2010 – 2012 ................................................... M.P.H. Health Promotion Department of Public Health Southern Connecticut State University 2011 – 2012 ................................................... Research Assistant, The Rudd Center for Food Policy and Obesity, New Haven, CT vii 2011 – 2012 ................................................... Graduate Research Fellow, Department of Public Health, Southern Connecticut State University 2012 – 2013 ................................................... Graduate Research Associate and Program Coordinator, Comprehensive Comprehensive Cancer Center The Ohio State University Medical Center 2013 – 2014 ................................................... Graduate Research Associate and Teaching Assistant, Division of Epidemiology College of Public Health The Ohio State University 2014 to present .............................................. Clinical Database Informatist, Department of Clinical Transformation, OhioHealth viii PUBLICATIONS Zigmont, V.A., Garrett A., Peng J., Seweryn M., Rempala G., Harris R., Holloman C., Karavodin L., Gundersen T., Ahlbom A., Feychting M., Johannesen T., Grimsrud T., and Schwartzbaum J. (2015). Association between Prediagnostic Serum 25- Hydroxyvitamin D Concentration and Glioma Risk among Older Men. Nutrition and Cancer. 67, 1120-30. Zigmont, V.A. and Bulmer S. M. (2015). The Impact of Caloric Knowledge on College Student's Fast Food Purchasing Intentions. The American Journal of Health Education, 46, 2, 70-78. Duplantier, A. J., Becker, S. L., Bohanon, M. J., Borzilleri, K. A., Chrunyk, B. A., Downs, J. T., Hu, L. H., El-Kattan, A., James, L. C., Liu, S., Lu, J., Maklad, N., Mansour, M. N., Mente, S., Piotrowski, M. A., Sakya, S. M., Sheehan, S., Steyn, S. J., Strick, C. A., Williams, V. A., & Zhang, L. (2009). 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