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 博士埃根是一名接受过临床内分泌学培训的医生，他将进行一项为期四年的指导研究， 职业发展计划在妊娠糖尿病（GDM）的病理生理学在马约诊所。她 将完成临床和转化科学硕士学位，获得体内 在产科人口的研究，获得分析和人体生理数据建模的新技能， 培养科学的领导能力和协作关系。这些活动将填补目前的空白， 知识，使埃根博士成为一名独立的临床研究者。埃根医生将由一个团队 具有相关专业知识的杰出研究人员，以及在指导年轻人方面的出色记录 教师。该团队将由她的主要导师Adrian Vella博士领导，他的研究重点是 2型糖尿病（T2 DM）的发病机制。GDM是一种常见的妊娠并发症， 产后相关高血糖消退，是T2 DM的强危险因素。几乎没有人理解 妊娠早期母体β细胞功能的变化，这如何预测妊娠后期的GDM，以及发生了什么变化 发生在产后。埃根博士的初步数据表明，α细胞的功能在怀孕期间也会发生变化，但 其在GDM发展和产后葡萄糖耐量中作用尚不清楚。在拟议的体内研究中，Dr. 埃根将确定β细胞（Aim 1）和α细胞（Aim 2）功能障碍的程度， 检查产后发生的胰岛细胞恢复（或缺乏）。埃根博士将评估GDM是否可以 在怀孕早期预测，这将有助于更及时的干预。她还将确认 产后一年仍存在的葡萄糖代谢缺陷。这些缺陷可能会导致 在GDM女性中观察到加速进展为T2 DM（目标3）。为了实现这些目标，埃根博士 将研究妇女在怀孕期间和产后使用国家的最先进的，非侵入性技术，以收集 并检查详细的生理数据为了与NIDDK的使命保持一致，拟议的研究将涉及 女性糖尿病发展的重要方面，并为未来的R 01应用提供基础 目的是开发新的糖尿病预防和治疗方法。