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

简介（由申请人提供）：Renata Belfort De Aguiar博士是耶鲁大学内分泌科内科讲师，对代谢和神经科学界面的转化临床研究感兴趣。Belfort De Aguiar博士对糖尿病和肥胖的发病机制特别感兴趣。在德克萨斯州圣安东尼奥市Ralph DeFronzo博士的实验室做研究期间，她接触到了用于人体研究的测量胰岛素抵抗的技术，包括高胰岛素正糖钳，以及使用葡萄糖示踪剂来评估葡萄糖代谢。随后，在耶鲁大学内分泌学的临床研究期间，她加入了罗伯特·谢温博士的实验室，参与了血糖水平对脑功能影响的研究。她在Sherwin博士的监督下进行的研究方案包括使用胰岛素钳技术，饮食行为问卷（从成瘾研究领域修改），以及通过结合视觉线索和功能性磁共振成像（fMRI）来测量大脑激活。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Todd Constable教授和耶鲁压力中心的Rajita Sinha教授合作。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（T2DM）患者在高血糖、正常血糖和低血糖水平。当看到视觉线索（食物和非食物图片）时，将用功能磁共振成像测量大脑活动。Belfort De Aguiar博士还计划评估减肥饮食如何影响2型糖尿病患者的大脑活动。该方案将帮助Belfort De Aguiar博士了解外周血糖水平对饮食行为的重要性，这可能与肥胖和2型糖尿病治疗策略的发展有关。从她的研究和临床研究中获得的专业知识为发展拟议的项目提供了必要的知识，但进一步的行为和神经影像学培训将是Belfort De Aguiar博士成为该领域独立内科科学家的基础。Belfort De Aguiar博士计划参加MRRC、耶鲁压力中心和耶鲁临床研究中心提供的课程，以帮助她在脑代谢和功能方面获得进一步的专业知识，包括：a)使用脑成像技术（fMRI、MRI光谱学和正电子发射断层扫描——所有这些都在耶鲁大学提供）；b)行为测量（功能磁共振成像视觉线索，问卷调查）。Belfort De Aguiar博士也将受益于与ctsa资助的耶鲁大学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，并促进她过渡到一个完全独立的临床研究者。如果授予

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.