Depression, antidepressant use and risk of diabetes in the WHI

描述(由申请人提供)：这项研究的总体目标是检查抑郁症或抗抑郁药物的使用是否与糖尿病风险的增加呈正相关。此外，我们将探索可能的机制，包括抑郁和抗抑郁药物的使用对体重、胰岛素、空腹血糖、高密度脂蛋白(HDL)、甘油三酯和炎症标志物的影响。绝经后妇女患抑郁症和糖尿病的比例越来越高，在美国老龄化人口中占很大比例。一项对九项纵向研究的荟萃分析发现，抑郁的成年人患糖尿病的风险增加37%。这一荟萃分析数据与最近的两项研究相矛盾，一项研究表明任何抗抑郁药的使用与糖尿病风险之间存在正相关，而抑郁评分升高与糖尿病风险无关；另一项研究表明，与TCA单一治疗相比，联合使用选择性5-羟色胺再摄取抑制剂(SSRI)和三环抗抑郁药(TCA)与显著增加糖尿病风险有关。有必要进行额外的分析，以检查抑郁症本身或特定类别和组合的抗抑郁药物是否预示着患糖尿病的风险。我们将使用从妇女健康倡议(WHI)收集的数据进行这项调查。从1993年到1998年，WHI在美国40个临床中心招募了年龄在50-79岁的普通健康绝经后女性(N=161,808，18%来自少数族裔)，并对她们进行了跟踪调查，直到2005年。随访7年以上，收集抗抑郁药物、抑郁和糖尿病状况。随访期保留率和资料收集完成率均在95%以上。在基线水平，15.8%的女性抑郁评分高于抑郁症筛查分界点，7.7%的女性正在服用抗抑郁药物。随访期间糖尿病年发病率为0.64%，累积发病率为4.6%。抗抑郁药物使用与糖尿病风险之间的研究对抗抑郁药物的新配方和糖尿病风险较高的女性具有重要意义。这项研究的方法论将涉及几个步骤：1)创建分析数据集；2)基于抑郁症或抗抑郁剂的使用与糖尿病发病风险之间的关系的分析来测试研究假设；3)基于抑郁症或抗抑郁剂的使用与体重和腰围的关系的分析来测试研究假设；4)基于抑郁或抗抑郁剂的使用与空腹血糖、胰岛素、高密度脂蛋白、甘油三酯和胰岛素抵抗的稳态模型评估(HOMA-IR)之间的关系的分析来测试研究假设；5)检查抑郁症或抗抑郁剂的使用与全身炎症标志物水平之间的关联；6)测试是否体重、腰围、空腹血糖、胰岛素、HOMA-IR、高密度脂蛋白胆固醇、甘油三酯和促炎细胞因子与糖尿病的风险有关；7)最终报告和手稿准备。 公共卫生相关性： 项目简介绝经后妇女患抑郁症和糖尿病的比例越来越高，在美国老龄化人口中占很大比例。使用从妇女健康倡议收集的数据，我们将调查抑郁症或抗抑郁药物的使用是否与糖尿病风险的增加呈正相关。此外，我们还将探索可能的机制。大约11%的美国女性正在服用抗抑郁药物。抗抑郁药物使用与糖尿病风险之间的研究对抗抑郁药物的新配方和糖尿病风险较高的女性具有重要意义。

DESCRIPTION (provided by applicant): 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.