Elucidating the Pathophysiology of Gestational Diabetes Mellitus

项目摘要/摘要 伊根博士是一名受过临床内分泌学培训的内科医生，将进行为期四年的指导性研究和 梅奥诊所妊娠期糖尿病(GDM)病理生理学的职业发展计划。她 将完成临床和翻译科学的硕士学位，获得体内操作的经验 在产科人群中进行研究，获得分析和模拟人体生理数据的新技能，以及 培养科学的领导技能和协作关系。这些活动将填补目前在 并允许伊根博士成为一名独立的临床研究员。伊根博士将由一个团队指导 拥有相关专业领域的杰出研究人员，并在指导年轻人方面有良好的记录 教职员工。这个团队将由她的主要导师禤浩焯·维拉博士领导，他的研究重点是 2型糖尿病的发病机制。妊娠期糖尿病是常见的妊娠并发症，而 产后合并高血糖可缓解，是T2 DM的重要危险因素。几乎没有人能理解 妊娠早期孕妇β细胞功能的变化，这可能如何预测妊娠晚期的妊娠期糖尿病，以及发生了什么变化 发生在产后。伊根博士的初步数据表明，α细胞功能在怀孕期间也会发生变化，但 它在妊娠期糖尿病发生和产后糖耐量中的作用尚不清楚。在拟议的活体研究中，Dr。 伊根将确定β细胞(目标1)和α细胞(目标2)功能障碍的程度，以产生妊娠期糖尿病和 检查产后发生的胰岛细胞恢复(或缺乏)。伊根博士将评估妊娠期糖尿病是否可以 在怀孕早期预测，这将有助于更及时的干预。她还将确定剩余的 产后持续一年的葡萄糖代谢缺陷。这些缺陷可能会导致 观察到妊娠期糖尿病妇女加速发展为T2 DM(目标3)。为了实现这些目标，伊根博士 将使用最先进的非侵入性技术研究怀孕和产后的女性 并检查详细的生理数据。根据NIDDK的使命，拟议的研究将涉及 女性糖尿病发展的重要方面，并为未来R01的应用奠定了基础 目标是开发新的糖尿病预防和治疗方法。

PROJECT SUMMARY/ABSTRACT Dr. Egan is a physician trained in clinical endocrinology and will undertake a four-year mentored research and career development program in the pathophysiology of gestational diabetes mellitus (GDM) at Mayo Clinic. She will complete a master’s degree in Clinical and Translational Science, gain experience in the conduct of in vivo studies in an obstetric population, acquire new skills in analysis and modeling of human physiological data, and develop scientific leadership skills and collaborative relationships. These activities will fill current gaps in knowledge and allow Dr. Egan to become an independent clinical investigator. Dr. Egan will be guided by a team of prominent researchers with relevant areas of expertise and an excellent track record in mentoring young faculty. This team will be led by her primary mentor, Dr Adrian Vella, whose research focuses on the pathogenesis of type 2 diabetes mellitus (T2DM). GDM is a common pregnancy complication and while the associated hyperglycemia resolves postpartum, it is a strong risk factor for T2DM. There is little understanding of maternal β-cell function in early pregnancy, how this may predict GDM in later pregnancy, and what changes occur postpartum. Dr. Egan’s preliminary data suggest that α-cell function also changes during pregnancy, but its role in GDM development and postpartum glucose tolerance is unknown. In the proposed in vivo studies, Dr. Egan will determine the degree of β-cell (Aim 1) and α-cell (Aim 2) dysfunction needed to produce GDM and examine the islet cell recovery (or lack thereof) that occurs postpartum. Dr. Egan will assess if GDM can be predicted earlier in pregnancy which would facilitate more timely intervention. She will also identify the residual defects in glucose metabolism that persist at one year postpartum. Such defects could contribute to the accelerated progression to T2DM observed in women with GDM (Aim 3). To accomplish these aims, Dr. Egan will study women during pregnancy and post-partum using state-of-the-art, non-invasive techniques to collect and examine detailed physiologic data. In keeping with the NIDDK mission, the proposed studies will address important aspects of diabetes development in women and provide the foundation for a future R01 application with the goal of developing novel diabetes prevention and treatment approaches.