NEURAL RESPONSE TO INSULIN RESISTANCE TREATMENTS

对胰岛素抵抗治疗的神经反应

基本信息

批准号：
8639565
负责人：
Jason J Hassenstab
金额：
$ 16.26万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8639565
关键词：
2,4-thiazolidinedione Adult Age Alzheimer&apos s Disease Amyloid beta-Protein Antidiabetic Drugs Award Behavior Therapy Bilateral Biological Markers Blood Pressure Blood Tests Body Composition Body Weight decreased Brain Brain region Cardiac Cardiovascular Diseases Clinical Trials Cognition Cognitive Control Groups Dementia Diet Disease Dorsal Educational workshop Endocrinology Enrollment Epidemic Episodic memory Euglycemic Clamping Event Functional Magnetic Resonance Imaging Functional disorder Glucose Glucose Clamp Goals Health Hippocampus (Brain)Hydrocortisone Individual Instruction Insulin Insulin Resistance Intervention K-Series Research Career Programs Knowledge acquisition Lateral Lead Learning Left Magnetic Resonance Imaging Master&apos s Degree Measures Memory Mentors Metabolic Methodology Monitor Neuropsychological Tests Non-Insulin-Dependent Diabetes Mellitus Obesity Oral Outcome Overweight Participant Patients Performance Pharmaceutical Preparations Pharmacological Treatment Physical activity Pioglitazone Process Psychometrics Quality of life Questionnaires Randomized Reaction Time Regulation Research Research Personnel Risk Short-Term Memory Sleep Apnea Syndromes Statistical Models System Techniques Testing Thiazolidinediones Training United States Universities Vasodilation Waiting Lists Washington Weight Weight Gain aged base cognitive function cognitive system college design executive function experience follow-up improved insulin sensitivity interest medical schools memory encoding middle age neuroimaging neuroinflammation neuropathology neuropsychological nutrition patient oriented prevent programs reconstruction relating to nervous system response responsible research conduct sedentary skill acquisition skills success treatment effect treatment strategy weight maintenance white matter

项目摘要

DESCRIPTION (provided by applicant): This is an application for a Mentored Patient-Oriented Career Development Award (K23). This award will provide the Applicant with advanced skills needed to establish an independent program of research in obesity and metabolic dysfunction using neuroimaging and neuropsychological methodologies. The proposed study will use fMRI, biomarkers of metabolic functioning, and neuropsychological tests to examine changes in cognition and brain response in obese and sedentary middle aged adults undergoing treatment for insulin resistance. We will enroll 75 obese participants who are participating in an existing study of weight reduction at the Nutrition and Obesity Research Center at Washington University Medical School. The participants will be randomly assigned to one of three conditions: 1) Six months of treatment with an oral thiazolidinedione medication (pioglitazone) to increase insulin sensitivity (n=25); 2) Six months of a standardized weight reduction intervention to achieve an 8-10% weight reduction and increased insulin sensitivity (n=25); or 3) A wait-list control group following 6 months of usual diet and weight maintenance (n=25). At baseline and follow- up, all participants will complete glucose clamp testing, body composition assessment, blood tests, blood pressure checks, comprehensive psychometric assessment, brief psychiatric assessment, physical activity questionnaires, and structural and functional MRI. The aims of the study are: 1) To determine if neuropsychological performance will improve as a function of increased insulin sensitivity and 2) To determine whether improved sensitivity to insulin will result in increased neural efficiency as measured by fMRI brain response. The Applicant proposes a comprehensive training plan, combining didactic instruction with established researchers; formal coursework including completion of a Master's Degree in Clinical Investigation; participation in several advanced workshops; participation in ongoing seminars at Washington University Medical School including the Nutrition and Obesity Research Seminar, the Knight Alzheimer's Disease Research Center; and applied training experiences with individual mentors. Specific training goals include advanced knowledge and skill acquisition in neuroimaging methodologies, including task-based fMRI, longitudinal approaches in fMRI, and structural MRI cortical reconstruction techniques. Training in advanced statistical modeling methodologies will also be provided by coursework and workshop participation. Additional coursework will be completed in nutrition, metabolism, endocrinology, multimodal neuroimaging, and the responsible conduct of research. The overall research goal of this proposal is to test the hypothesis that improved insulin sensitivity achieved through weight reduction or thiazolidinedione treatment is accompanied by beneficial changes in cognitive performance and fMRI brain response.

描述（由申请人提供）：这是一份以患者为导向的职业发展奖（K23）的申请。该奖项将为申请人提供使用神经影像学和神经心理学方法建立肥胖和代谢功能障碍独立研究项目所需的先进技能。拟议的研究将使用功能磁共振成像、代谢功能的生物标志物和神经心理学测试来检查接受胰岛素抵抗治疗的肥胖和久坐的中年人的认知和大脑反应的变化。我们将招募 75 名肥胖参与者，他们正在参加华盛顿大学医学院营养与肥胖研究中心现有的一项减肥研究。参与者将被随机分配到以下三种情况之一：1）接受六个月的口服噻唑烷二酮药物（吡格列酮）治疗以增加胰岛素敏感性（n = 25）； 2) 六个月的标准化减重干预，实现体重减轻 8-10% 并提高胰岛素敏感性 (n=25)；或 3) 6 个月正常饮食和体重维持后的等待名单对照组 (n=25)。在基线和随访时，所有参与者将完成葡萄糖钳夹测试、身体成分评估、血液测试、血压检查、综合心理评估、简要精神病学评估、身体活动问卷以及结构和功能 MRI。该研究的目的是：1）确定神经心理学表现是否会随着胰岛素敏感性的增加而改善；2）确定胰岛素敏感性的提高是否会导致通过功能磁共振成像大脑反应测量的神经效率增加。申请人提出全面的培训计划，将教学指导与现有研究人员相结合；正式课程，包括完成临床研究硕士学位；参加多个高级研讨会；参加华盛顿大学医学院正在进行的研讨会，包括营养与肥胖研究研讨会、奈特阿尔茨海默病研究中心；以及个人导师的应用培训经验。具体的培训目标包括神经影像方法学方面的高级知识和技能获取，包括基于任务的功能磁共振成像、功能磁共振成像的纵向方法和结构磁共振成像皮层重建技术。高级统计建模方法的培训也将通过课程作业和研讨会参与提供。额外的课程将完成营养、新陈代谢、内分泌学、多模式神经影像学和负责任的研究行为。该提案的总体研究目标是检验以下假设：通过减轻体重或噻唑烷二酮治疗来改善胰岛素敏感性，同时伴随认知表现和功能磁共振成像大脑反应的有益变化。