The overall goal of this study is to examine whether depression or antidepressant medication use are positively associated with an increased risk of developing diabetes. In addition, we will explore possible mechanisms including depression and antidepressant medication use on body weight, insulin, fasting glucose, high-density lipoprotein (HDL), triglycerides, and inflammation markers. Postmenopausal women have an increasing prevalence of depression and diabetes and constitute a large percentage of the aging population in the United States. A meta-analysis of nine longitudinal studies found that depressed adults had a 37% increased risk of developing diabetes. This meta-analytic data conflicts with two recent studies, one demonstrated a positive association between any antidepressant use and diabetes risk, while elevated depression scores were not associated with diabetes risk;another study demonstrated that combined use of selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) was associated with a significantly increased risk of diabetes compared with TCA monotherapy. Additional analysis is necessary to examine whether depression itself or specific classes and combinations of antidepressant medication predicts a risk of developing diabetes. We will use data collected from the Women's Health Initiative (WHI) for this investigation. The WHI recruited general healthy postmenopausal women (N=161,808, 18% from ethnic minority groups) aged 50-79 at 40 clinical centers across the U.S from 1993-1998, and followed them until 2005. Antidepressant medication, depression and diabetes status were collected over 7 years of follow-up. The rates of retention and data collection completion were over 95% during the follow-up. At baseline, 15.8% of women had depression scores above the screening cutoff point for depression and 7.7% were taking antidepressant medications. During follow-up, the annual diabetes incidence was 0.64% and the cumulative incidence was 4.6%. The investigation between antidepressant use and diabetes risk have implications for new formulations of antidepressants and for women at heightened risk for diabetes. The methodology of this proposed study will involve several steps: 1) Creating analytical data sets;2) Testing study hypotheses based on the analyses of relationships between depression or antidepressant use and risk of developing diabetes;3) Testing study hypotheses based on the analyses of relationships of depression or antidepressant use with body weight and waist circumference;4) Testing study hypotheses based on the analyses of relationships between depression or antidepressant use and fasting glucose, insulin, HDL, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR);5) Examination the association between depression or antidepressant use and levels of systemic inflammation markers;6) Testing whether risk of diabetes from depression or antidepressant medication use is mediated by body weight, waist circumference, fasting glucose, insulin, HOMA-IR, HDL cholesterol, triglycerides, and proinflammatory cytokines;and 7) Final report and manuscript preparation.

Public Health Relevance

Project Narrative Postmenopausal women have an increasing prevalence of depression and diabetes and constitute a large percentage of the aging population in the United States. Using data collected from the Women's Health Initiative, we will investigate whether depression or antidepressant medication use are positively associated with an increased risk of developing diabetes. In addition, we will explore possible mechanisms. Approximately 11% of American women are taking antidepressant medication. The investigation between antidepressant use and diabetes risk have implications for new formulations of antidepressants and for women at heightened risk for diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK083700-01A1
Application #
7788392
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Staten, Myrlene A
Project Start
2010-02-05
Project End
2012-01-31
Budget Start
2010-02-05
Budget End
2011-01-31
Support Year
1
Fiscal Year
2010
Total Cost
$220,010
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Tabung, Fred K; Steck, Susan E; Ma, Yunsheng et al. (2015) The association between dietary inflammatory index and risk of colorectal cancer among postmenopausal women: results from the Women's Health Initiative. Cancer Causes Control 26:399-408
Frisard, Christine; Gu, Xiangdong; Whitcomb, Brian et al. (2015) Marginal structural models for the estimation of the risk of Diabetes Mellitus in the presence of elevated depressive symptoms and antidepressant medication use in the Women's Health Initiative observational and clinical trial cohorts. BMC Endocr Disord 15:56
Sambamoorthi, Usha; Ma, Yunsheng; Findley, Patricia A et al. (2013) Antidepressant use, depression, and new-onset diabetes among elderly Medicare beneficiaries. J Diabetes 5:327-35
Ma, Yunsheng; Balasubramanian, Raji; Pagoto, Sherry L et al. (2013) Relations of depressive symptoms and antidepressant use to body mass index and selected biomarkers for diabetes and cardiovascular disease. Am J Public Health 103:e34-43
Ma, Yunsheng; Hébert, James R; Balasubramanian, Raji et al. (2013) All-cause, cardiovascular, and cancer mortality rates in postmenopausal white, black, Hispanic, and Asian women with and without diabetes in the United States: the Women's Health Initiative, 1993-2009. Am J Epidemiol 178:1533-41
Ma, Yunsheng; Culver, Annie; Rossouw, Jacques et al. (2013) Statin therapy and the risk for diabetes among adult women: do the benefits outweigh the risk? Ther Adv Cardiovasc Dis 7:41-4
Ma, Yunsheng; Hébert, James R; Manson, Joann E et al. (2012) Determinants of racial/ethnic disparities in incidence of diabetes in postmenopausal women in the U.S.: The Women's Health Initiative 1993-2009. Diabetes Care 35:2226-34
Culver, Annie L; Ockene, Ira S; Balasubramanian, Raji et al. (2012) Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med 172:144-52
Ma, Yunsheng; Balasubramanian, Raji; Pagoto, Sherry L et al. (2011) Elevated depressive symptoms, antidepressant use, and diabetes in a large multiethnic national sample of postmenopausal women. Diabetes Care 34:2390-2
Ma, Yunsheng; Chiriboga, David E; Pagoto, Sherry L et al. (2010) Association between Depression and C-Reactive Protein. Cardiol Res Pract 2011:286509