Effect of Circulating Glucose on Eating Behavior and Brain Activation in Diabetes

描述(申请人提供)：Renata Belfort de Aguiar博士是耶鲁大学内科内分泌科的讲师，对新陈代谢和神经科学之间的转化性临床研究感兴趣。贝尔福·德·阿吉亚尔博士对糖尿病和肥胖症的发病机制特别感兴趣。在德克萨斯州圣安东尼奥的拉尔夫·德弗兰佐博士的实验室担任研究员期间，她被介绍给人类研究中用于测量胰岛素抵抗的技术，包括高胰岛素正血糖钳夹，以及使用葡萄糖示踪剂来评估葡萄糖代谢。随后，在耶鲁大学担任内分泌学临床研究员期间，她加入了罗伯特·舍温博士的实验室，并参与了血糖水平对大脑功能影响的研究。她在舍温博士的监督下进行的研究包括使用胰岛素夹技术、饮食行为问卷(从成瘾研究领域修改而来)，以及通过结合视觉线索和功能磁共振成像(FMRI)测量大脑激活。为了执行这些研究项目，Belfort de Aguiar博士与磁共振研究中心(MRRC)的托德·康斯特布尔教授和耶鲁大学压力中心的Rajita Sinha教授合作。通过使用上述技术，Belfort de Aguiar博士计划研究正常体重、肥胖和2型糖尿病(T2 DM)患者在高、正常和低血糖水平时的情况。当看到视觉提示(食物和非食物图片)时，将使用功能磁共振来测量大脑的激活。贝尔福·德·阿吉亚尔博士还计划评估减肥饮食将如何影响T2 DM受试者的大脑激活。该方案将帮助Belfort de Aguiar博士理解外周血糖水平对食物行为的重要性，这可能与肥胖症和T2 DM治疗策略的制定相关。从她的研究和临床奖学金中获得的专业知识为开发拟议的项目提供了必要的知识，但进一步的行为和神经成像培训将是Belfort de Aguiar博士成为该领域独立内科科学家的基础。贝尔福·德·阿吉亚尔博士计划参加MRRC、耶鲁大学压力中心和耶鲁临床中心调查中心开设的课程，以帮助她获得大脑新陈代谢和功能方面的进一步专业知识，包括：a)脑成像技术的使用(功能磁共振成像、核磁共振波谱和正电子发射断层扫描--均可在耶鲁大学获得)；以及b)行为测量(功能磁共振成像的视觉线索、问卷)。Belfort de Aguiar博士还将受益于与CTSA资助的耶鲁分析科学中心的合作，以协助收集和分析数据。这个具体的项目将给她撰写论文和在科学会议上展示结果的经验，这将有助于她的学术发展，并促进她向完全独立的临床研究员的过渡。如果批准的话 此次获奖，Belfort de Aguiar博士将能够实现她的长期职业目标，即成为神经科学/新陈代谢领域的临床翻译科学家。

DESCRIPTION (provided by applicant): Dr. Renata Belfort De Aguiar is an Instructor in the Department of Internal Medicine, Section of Endocrinology, at Yale University with an interest in translational clinical research at the interface between metabolism and neuroscience. Dr. Belfort De Aguiar is particularly interested in the pathogenesis of diabetes and obesity. During her research fellowship in the laboratory of Dr. Ralph DeFronzo in San Antonio, Texas, she was introduced to techniques used in human studies to measure insulin resistance, including the hyperinsulinemic euglycemic clamp, and the use of glucose tracers to evaluate glucose metabolism. Subsequently, during her clinical fellowship in endocrinology at Yale University, she joined the laboratory of Dr. Robert Sherwin and got involved in studies looking at the influence of blood glucose levels on brain function. The research protocols she has worked under Dr. Sherwin's supervision, involved the use of the insulin clamp technique, eating behavior questionnaires (modified from the addiction research field), and measurement of brain activation by combining visual cues and functional Magnetic Resonance Imaging (fMRI). For the execution of these research projects, Dr. Belfort De Aguiar has collaborated with Professor Todd Constable from the Magnetic Resonance Research Center (MRRC) and Professor Rajita Sinha from the Yale Stress Center. With the use of the techniques described above, Dr. Belfort De Aguiar plans to study normal weight, obese, and patients with type 2 diabetes (T2DM) during high, normal and low blood glucose levels. Brain activation will be measured with fMRI while seeing visual cues (food and non-food pictures). Dr. Belfort De Aguiar also plans to evaluate how weight loss diet will affect brain activation in T2DM subjects. This protocol will help Dr. Belfort De Aguiar to understand the importance of peripheral glucose levels on food behavior, which may be relevant for development of strategies in the treatment of obesity and T2DM. The expertise attained from her research and clinical fellowships have provided the necessary knowledge to develop the proposed project, but further training in behavioral and neuroimaging will be fundamental to Dr. Belfort De Aguiar to become an independent physician scientist in this field. Dr. Belfort De Aguiar is planning to attend courses offered at the MRRC, Yale Stress Center and Yale Clinical Center Investigation to help her gain further expertise in brain metabolism and function including: a) use of brain imaging techniques (fMRI, MRI spectroscopy and positron emission tomography - all available at Yale University); and b) behavioral measurements (visual cues with fMRI, questionnaires). Dr. Belfort De Aguiar will also benefit of the collaboration with the CTSA-funded Yale Center for Analytical Sciences to assist with the collection and analysis of the data. This specific project will give her experience with writing papers and presenting the results at scientific meetings, which will contribute to her academic development, and facilitate her transition to a fully independent clinical investigator. If granted this award, Dr. Belfort De Aguiar will be able to achieve her long term career goal of becoming a clinical translational scientist in the field of neuroscience/metabolism.