Elucidating the Pathophysiology of Gestational Diabetes Mellitus

阐明妊娠糖尿病的病理生理学

• 批准号: 10738361
• 负责人: Aoife Maria Egan
• 金额: $ 19.06万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10738361
• 关键词: Acceleration; Affect; Alpha Cell; Area; Autopsy; Beta Cell; C-Peptide; Cell physiology; Clinic; Clinical Endocrinology; Clinical Investigator; Clinical Sciences; Compensation; Data; Defect; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Discipline of obstetrics; Faculty; Fasting; Fetal Growth; First Pregnancy Trimester; Foundations; Functional disorder; Future; Gestational Diabetes; Glucagon; Glucose; Goals; Health; Human; Hyperglycemia; Impairment; Individual; Insulin; Intervention; Islet Cell; Islets of Langerhans; Knowledge; Late pregnancy; Leadership; Master of Science; Measurement; Measures; Mediating; Mentors; Metabolic; Methodology; Mission; Modeling; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Oral; Overweight; Pathogenesis; Pathway interactions; Physicians; Physiological; Population; Postpartum Period; Pregnancy; Pregnancy Complications; Prevention; Prevention strategy; Program Development; Prospective Studies; Prospective, cohort study; Recovery; Reproducibility; Research; Research Personnel; Residual state; Resolution; Risk; Risk Factors; Role; Sampling; Sensitivity and Specificity; Techniques; Testing; Time; Tracer; Training; Translational Research; United States; Woman; Work; adverse pregnancy outcome; blood glucose regulation; career development; clinical risk; cohort; early pregnancy; effective intervention; experience; glucose disposal; glucose metabolism; glucose production; glucose tolerance; glycemic control; high risk; human data; human model; improved; in vivo; indexing; insight; insulin secretion; insulin sensitivity; islet; novel; novel strategies; post pregnancy; research and development; risk stratification; skills; tool; treatment strategy

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.

项目摘要/摘要 伊根（Egan）博士是接受临床内分泌学培训的物理培训，将进行四年的修订研究和 Mayo诊所妊娠糖尿病（GDM）病理生理学的职业发展计划。她 将完成临床和转化科学的硕士学位，并获得体内行为的经验 在产科人群中的研究，在人类生理数据的分析和建模方面获得新技能，以及 发展科学领导能力和协作关系。这些活动将填补当前空白 知识并允许Egan博士成为独立的临床研究者。埃根博士将由团队指导 具有专家相关领域的著名研究人员和精神上的良好记录 学院。该团队将由她的主要导师阿德里安·维拉（Adrian Vella）领导，他的研究重点是 2型糖尿病（T2DM）的发病机理。 GDM是常见的妊娠并发症，而 相关的高血糖可以解决产后，这是T2DM的强大危险因素。几乎没有理解 孕妇在怀孕初期的母体β细胞功能，这如何预测后期怀孕的GDM，以及什么变化 发生产后。 Egan博士的初步数据表明，怀孕期间的α细胞功能也会发生变化，但 它在GDM发育中的作用和产后葡萄糖耐受性尚不清楚。在拟议的体内研究中，博士 EGAN将确定产生GDM和 检查发生产后发生的胰岛细胞恢复（或缺乏）。 Egan博士将评估GDM是否可以 预测在怀孕早期，这将有助于更及时的干预。她还将确定残留 产后一年的葡萄糖代谢缺陷。这样的缺陷可能有助于 在GDM女性中观察到的加速对T2DM的进展（AIM 3）。为了实现这些目标，埃根博士 将在怀孕期间使用最先进的非侵入性技术来研究妇女 并检查详细的生理数据。为了与NIDDK任务保持一致，拟议的研究将解决 妇女糖尿病发展的重要方面，为未来的R01申请奠定了基础 目的是开发新型糖尿病预防和治疗方法。