Sex Hormones in Postmenopausal Women in the Diabetes Prevention Program

糖尿病预防计划中绝经后妇女的性激素

• 批准号: 8098763
• 负责人: CATHERINE KIM
• 金额: $ 20.17万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8098763
• 关键词: Address; Adipose tissue; Adult; Affect; Aging; Ancillary Study; Androgens; Anthropometry; Biological Factors; Biological Markers; Biology; Body Composition; Body Weight decreased; Caucasians; Caucasoid Race; Chronic; Clinic; Clinical Trials Design; Consent; Data; Data Collection; Deterioration; Diabetes Mellitus; Diabetes prevention; Disease; Enrollment; Epidemiologic Studies; Epidemiologist; Epidemiology; Estradiol; European; Evolution; Exogenous Hormone Therapy; Fasting; Fatty acid glycerol esters; Female; Follicle Stimulating Hormone; Functional disorder; Funding; Future; Glucose; Glucose Intolerance; Goals; Gonadal Steroid Hormones; Health; Hepatic; High Risk Woman; Homeostasis; Hormone replacement therapy; Hormones; Impaired fasting glycaemia; Individual; Insulin; Insulin Resistance; Intervention; Intervention Studies; Investigation; Life; Life Style; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Measures; Mediator of activation protein; Menopause; Metabolism; Metformin; National Institute of Diabetes and Digestive and Kidney Diseases; Native Americans; Nature; Obesity; Observational Study; Organ; Ovarian; Participant; Pathway interactions; Performance; Placebos; Plasma; Play; Population; Population Heterogeneity; Positioning Attribute; Postmenopause; Premenopause; Prevention strategy; Preventive Intervention; Randomized; Randomized Controlled Trials; Research; Research Personnel; Resources; Risk; Role; Serum; Sex Hormone-Binding Globulin; Site; Skeletal Muscle; Socioeconomic Status; Staging; Stratification; Testosterone; Visit; Woman; Women' s Health; Work; abdominal fat; arm; base; clinically significant; cohort; cost effective; diabetes prevention program; diabetes risk; experience; follow-up; glucose metabolism; glucose tolerance; impaired glucose tolerance; insight; insulin secretion; insulin sensitivity; lifestyle intervention; men; novel marker; public health relevance; randomized trial

DESCRIPTION (provided by applicant): Although postmenopause is a universal experience of aging and is defined by permanent changes in ovarian function, we still do not understand how postmenopausal sex hormones affect diabetes risk. Intriguing observations suggest that endogenous sex hormones (ESH) may contribute to glucose intolerance in postmenopausal women. Previous observational studies have been limited by single measures of ESH, and intervention studies are limited by examination of exogenous hormone only, lack of significant glucose changes, lack of measurement of potential confounders such as insulin homeostasis, or examination only in Caucasians of European ancestry. The Diabetes Prevention Program (DPP) was a large randomized controlled trial (n=3,234) of intensive lifestyle intervention and metformin for prevention of diabetes. The DPP enrolled participants with either impaired fasting glucose or impaired glucose tolerance, 45% of whom were non-white, and the DPP also obtained multiple measures of anthropometry, insulin secretion, insulin sensitivity, and fasting and postchallenge glucose. Approximately two-thirds were women, and half of the women were postmenopausal at baseline. Thus, the DPP offers a compelling opportunity to examine the contribution of changes in endogenous sex hormones (ESH) to the evolution of glucose intolerance in postmenopausal women. We propose an ancillary study to the DPP, the Sex Hormones in Postmenopausal Women or SHIP study. Using plasma stored from the baseline data collection and 2 years after randomization, we propose to examine ESH (testosterone, estradiol, sex hormone binding globulin) and follicle stimulating hormone (FSH) in a subset of DPP women without exogenous hormone use (n=865) and DPP women with exogenous hormone use (n=144) using state-of-the art mass spectrometry. Specific Aim 1 is to examine if diabetes prevention interventions are associated with changes in ESH. Specific Aim 2 is to examine if changes in ESH levels are associated with changes in glucose by intervention arm. Specific Aim 3 is to examine whether changes in adiposity, insulin sensitivity, and insulin secretion explain these associations. Investigators and consultants on this proposal are involved in the Study of Women's Health Across the Nation expert in ESH life stage transitions, as well as DPP PIs who have conducted the initial research in ESH that form the basis for this study. The team includes sex hormone biologists, epidemiologists, and diabetologists. The DPP and its follow-up study are supported by the NIDDK. Ongoing management of DPP resources occurs through the DPP Coordinating Center, and the SHIP study will be complementary to ongoing DPP ancillary studies examining androgens in premenopausal women and androgens in men. The DPP's large, well-characterized, racially/ethnically diverse population and stored plasma provide a unique opportunity to assess the relationships among repeated measures of ESH, adiposity, insulin homeostasis, and glucose intolerance. PUBLIC HEALTH RELEVANCE: Postmenopausal women are at high risk for diabetes, and previous studies suggest that endogenous sex hormones (as opposed to hormone replacement therapy) may play a role. However, previous studies have not examined whether changes in sex hormones are associated with changes in glucose tolerance, and whether such changes might be explained by concurrent changes in adiposity and insulin. Previous studies have not examined the influence of diabetes prevention interventions upon sex hormones. To address these gaps, the proposed SHIP ancillary study will leverage the significant data already collected through the DPP. The SHIP study will provide insight into the pathophysiology of glucose intolerance, and the findings will have implications not only for diabetes prevention but also for other diseases that focus on sex hormones as mediators.

描述（由申请人提供）：尽管绝经后是一种普遍的衰老经历，并且由卵巢功能的永久性变化来定义，但我们仍然不了解绝经后性激素如何影响糖尿病风险。有趣的观察结果表明，内源性激素（ESH）可能导致绝经后妇女出现葡萄糖不耐受。先前的观察性研究受到ESH单一测量的限制，而干预研究则受到仅检查外源性激素、缺乏显着的血糖变化、缺乏对胰岛素稳态等潜在混杂因素的测量或仅在欧洲血统的白种人中进行检查的限制。糖尿病预防计划 (DPP) 是一项大型随机对照试验 (n=3,234)，研究强化生活方式干预和二甲双胍预防糖尿病。 DPP 招募了空腹血糖受损或糖耐量受损的参与者，其中 45% 是非白人，DPP 还获得了人体测量、胰岛素分泌、胰岛素敏感性以及空腹和挑战后血糖的多项测量数据。大约三分之二是女性，其中一半女性在基线时已绝经。因此，DPP 提供了一个令人信服的机会来研究内源性激素 (ESH) 的变化对绝经后妇女葡萄糖耐受不良演变的影响。我们建议对 DPP（绝经后妇女性激素或 SHIP 研究）进行一项辅助研究。使用从基线数据收集和随机化后 2 年存储的血浆，我们建议在未使用外源激素的 DPP 女性子集中检查 ESH（睾酮、雌二醇、性激素结合球蛋白）和卵泡刺激素 (FSH)（n=865） ）和使用外源性激素的 DPP 女性 (n=144)，使用最先进的质谱分析法。具体目标 1 是检查糖尿病预防干预措施是否与 ESH 变化相关。具体目标 2 是检查 ESH 水平的变化是否与干预组的血糖变化相关。具体目标 3 是检查肥胖、胰岛素敏感性和胰岛素分泌的变化是否可以解释这些关联。该提案的研究人员和顾问参与了全国妇女健康研究、ESH 生命阶段转变方面的专家，以及 DPP PI，他们进行了 ESH 方面的初步研究，这些研究构成了本研究的基础。该团队包括性激素生物学家、流行病学家和糖尿病学家。 DPP 及其后续研究得到了 NIDDK 的支持。 DPP 资源的持续管理是通过 DPP 协调中心进行的，SHIP 研究将补充正在进行的 DPP 辅助研究，该研究检查绝经前女性的雄激素和男性的雄激素。 DPP 庞大、特征明确、种族/民族多样化的人口和储存的血浆提供了独特的机会来评估 ESH、肥胖、胰岛素稳态和葡萄糖耐受不良的重复测量之间的关系。 公共健康相关性：绝经后妇女患糖尿病的风险很高，之前的研究表明内源性激素（而不是激素替代疗法）可能发挥作用。然而，之前的研究尚未检验性激素的变化是否与糖耐量的变化有关，以及这种变化是否可以通过肥胖和胰岛素的同时变化来解释。之前的研究尚未检验糖尿病预防干预措施对性激素的影响。为了解决这些差距，拟议的 SHIP 辅助研究将利用 DPP 已经收集的重要数据。 SHIP 研究将深入了解葡萄糖不耐症的病理生理学，其研究结果不仅对糖尿病预防有影响，而且对以性激素为介质的其他疾病也有影响。