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: 7983696
• 负责人: CATHERINE KIM
• 金额: $ 75.02万
• 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/7983696
• 关键词: Address; Adipose tissue; Adult; Affect; Aging; Ancillary Study; Androgens; Anthropometry; Arts; 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; Follow-Up Studies; 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; Osteoporosis; 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; diabetes prevention program; diabetes risk; experience; glucose metabolism; glucose tolerance; impaired glucose tolerance; insight; insulin secretion; insulin sensitivity; lifestyle intervention; men; novel marker; public health relevance; randomized trial; Address; Adipose tissue; Adult; Affect; Aging; Ancillary Study; Androgens; Anthropometry; Arts; 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; Follow-Up Studies; 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; Osteoporosis; 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; diabetes prevention program; diabetes risk; experience; 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）：尽管绝经后是衰老的普遍经验，并且是由卵巢功能的永久变化定义的，但我们仍然不了解绝经后性激素如何影响糖尿病的风险。有趣的观察表明，内源性激素（ESH）可能导致绝经后妇女的葡萄糖不耐症。先前的观察性研究受到了ESH的单一测量的限制，干预研究仅受外源激素的检查，缺乏明显的葡萄糖变化，缺乏对潜在混杂因素（例如胰岛素稳态）的测量或仅在欧洲血统的白种人中进行检查。糖尿病预防计划（DPP）是一项大型随机对照试验（n = 3,234），即强化生活方式干预和预防糖尿病的二甲双胍。 DPP招募的禁食葡萄糖或葡萄糖耐受性受损的参与者，其中45％是非白人，而DPP还获得了人体测量法，胰岛素分泌，胰岛素敏感性，禁食和挑战后葡萄糖的多种测量方法。大约三分之二的是女性，一半的妇女是基线后的绝经后。因此，DPP提供了一个令人信服的机会，可以检查内源性激素（ESH）对绝经后妇女葡萄糖不耐症的进化的贡献。我们向DPP提出了一项辅助研究，即绝经后妇女的性激素或船舶研究。使用基线数据收集的血浆和随机分组后的2年，我们建议检查ESH（睾丸激素，雌激素，性激素结合球蛋白）和卵泡刺激激素（FSH）中的DPP女性中没有外源激素使用（n = 865）（n = 865）的DPP女性（n = 865），以及使用量身强激素的DPP妇女使用量的ESH，并使用了使用量的ESH激素（n = 865）和使用量的spetion spete n = 144）。具体目的1是检查预防糖尿病是否与ESH的变化有关。具体目标2是检查ESH水平的变化是否与干预组的葡萄糖变化有关。具体目的3是检查肥胖，胰岛素敏感性和胰岛素分泌的变化是否解释了这些关联。有关该提案的研究人员和顾问参与了全国妇女健康专家的ESH Life阶段过渡的研究，以及在ESH中进行了初步研究的DPP PI，这是本研究的基础。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资源的持续管理通过DPP协调中心进行，船舶研究将与正在进行的DPP辅助研究相辅相成，研究了男性绝经前女性和雄激素的雄激素。 DPP的大型，良好的，种族/种族的种群和存储的血浆提供了一个独特的机会，可以评估ESH重复测量，肥胖，胰岛素稳态和葡萄糖不耐症之间的关系。 公共卫生相关性：绝经后妇女患糖尿病的风险很高，先前的研究表明，内源性激素（而不是激素替代疗法）可能起作用。但是，以前的研究尚未检查性激素的变化是否与葡萄糖耐受性的变化有关，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。先前的研究尚未检查糖尿病预防干预措施对性激素的影响。为了解决这些差距，拟议的船舶辅助研究将利用已经通过DPP收集的重要数据。该船研究将洞悉葡萄糖不耐症的病理生理学，这些发现不仅对预防糖尿病有影响，而且还对其他针对性激素作为介体的疾病也有影响。