POLYCYSTIC OVARY SYNDROME: ROLE OF INSULIN RESISTANCE

职位描述(申请人提供)：这位职业生涯中期的K24调查员 以患者为本的研究奖申请是为了支持继续 约翰·E·内斯特勒博士作为临床研究员和研究人员的发展 门托。内斯特勒博士是弗吉尼亚联邦大学的医学教授 弗吉尼亚大学医学院，一直是一位富有成效的患者- 其研究重点一直是血管紧张素转换酶的病理生理学作用 多囊卵巢综合征(PCOS)的胰岛素抵抗 影响6%-10%的育龄妇女。内斯特勒博士还有一个 建立了对年轻临床研究人员的指导记录。这个 内斯特勒博士研究的广泛长期目标一直是进行这两项工作 探索胰岛素抵抗作用的机制和翻译研究 在多囊卵巢综合征中。本申请书中建议的具体研究，包括 目前由NIH R01拨款和U54拨款资助，旨在1)到 确定慢性胰岛素减少对自发性和自发性高血压发生率的影响 克罗米芬诱导多囊卵巢综合征患者排卵的研究 对克罗米芬诱导无效；2)确定是否减少 血清胰岛素浓度对促性腺激素分泌的影响 动力学(即，降低促黄体激素脉冲幅度和/或脉冲 在患有多囊卵巢综合征的肥胖和/或消瘦女性中)；以及3)探索 胰岛素抵抗会导致不良的心血管风险 在绝经前有多囊卵巢综合征病史的绝经后妇女。 这些研究将在综合临床研究中心进行，使用 最先进的方法，例如每10分钟采一次血 基于聚类、去卷积分析和近似的激素脉搏分析 和Reaven的稳态血糖(SSPG)技术 纵向监测胰岛素敏感性。K24奖将促进 这些研究的完成，同时也使内斯特勒博士有可能 以促进他作为临床研究人员的个人成长，并增加他的 辅导活动。它将通过为内斯特勒博士提供更多的 受保护时间，因行政职责减少和 临床服务职责。作为K24奖的结果，内斯特勒博士 能够将80%的精力投入到研究、进一步的个人培训中 临床研究，以及对年轻研究人员的培训和指导。

DESCRIPTION (provided by applicant): This K24 Mid-Career Investigator in Patient-Oriented Research Award application is to support the continue development of Dr. John E. Nestler as a clinical investigator and research mentor. Dr. Nestler is Professor of Medicine at Virginia Commonwealth University's Medical College of Virginia, and has been a productive patient- oriented researcher whose research focus has been the pathophysiologic role of insulin resistance in the polycystic ovary syndrome (PCOS), a disorder that affects 6-10% of women of childbearing age. Dr. Nestler also has an established track record of mentorship of young clinical investigators. The broad long-term objective of Dr. Nestler's studies has been to conduct both mechanistic and translational studies exploring the role of insulin resistance in PCOS. The specific studies proposed in this application, which are currently funded by an NIH R0l grant and a U54 grant, are designed 1) to determine the effects of chronic insulin reduction on rates of spontaneous and clomiphene-induced ovulation in women with PCOS who were previously found to be refractory to clomiphene induction; 2) to determine whether reducing the serum insulin concentration beneficially influences gonadotropin secretory dynamics (i.e., decreases luteinizing hormone pulse amplitude and/or pulse frequency) in obese and/or lean women with PCOS; and 3) to explore whether insulin resistance causes an adverse cardiovascular risk profile in postmenopausal women with a history of PCOS during the premenopausal period. These studies will be conducted on the General Clinical Research Center using state-of-the-art methodologies, such as every 10 minute blood sampling for hormone pulse analysis by Cluster, Deconvolution Analysis and Approximate Entropy, and Reaven's steady-state plasma glucose (SSPG) technique for longitudinally monitoring insulin sensitivity. The K24 award will facilitate the completion of these studies, while also making it possible for Dr. Nestler to enhance his personal growth as a clinical investigator and to increase his mentoring activities. It will do so by providing Dr. Nestler with increased protected time, resulting from a decrease in administrative duties and clinical service responsibilities. As a result of the K24 award, Dr. Nestler will be able to devote 80% effort to research, further personal training in clinical research, and the training and mentorship of young investigators.