Beta Cell Restoration through Fat Mitigation

通过减脂恢复β细胞

• 批准号: 8247932
• 负责人: Thomas A Buchanan
• 金额: $ 68.4万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-23 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247932
• 关键词: Abdomen; Address; Adipose tissue; Adult; Adverse effects; Agreement; Allergens; Behavior Therapy; Behavioral; Beta Cell; Biological; Biological Preservation; Biology; Body Weight decreased; Body fat; Bypass; Cell physiology; Cells; Cellular biology; Chronic; Clinical; Clinical Markers; Clinical Research; Clinical Trials; Critiques; DEXA; Deltastab; Deterioration; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Face; Failure; Fasting; Fatty acid glycerol esters; Financial compensation; Funding; Future; Health; Hispanic Americans; Hispanics; Human; Individual; Inflammation; Insulin Resistance; Knowledge; Life Style; Link; Long-Term Effects; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Medical; Metabolic; Methods; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Outcome; Pancreas; Pattern; Pharmaceutical Preparations; Pioglitazone; Positioning Attribute; Prediabetes syndrome; Prevention strategy; Primitive foregut structure; Published Comment; Randomized; Research; Risk Factors; Secure; Testing; United States National Institutes of Health; Weight; Weight Gain; Work; adiponectin; arm; bariatric surgery; base; clinical care; cost; cost effective; diabetes risk; effective therapy; falls; improved; insulin secretion; obesity treatment; operation; peer; prevent; primary outcome; programs; prospective; protective effect; response marker; restoration; success; therapeutic target

DESCRIPTION (provided by applicant): The long-term objective of our research program is to understand causes of and develop treatments for the progressive ¿-cell disease that causes type 2 diabetes (T2D). Our prior work and research by others provides important evidence that metabolic effects of obesity cause ¿-cell failure. Lifestyle changes and medications that alter body fat or its biology appear to slow or stop p-cell deterioration in some people, but not most. We hypothesize that substantial weight loss induced by gastric banding will be more effective than the best available medication, pioglitazone, in preserving or restoring ¿-cell function. We propose a 2-arm, unblinded study to compare gastric banding to treatment with pioglitazone over a 24-month period in moderately obese Hispanic adults with pre- or mild T2D. The primary outcome will be change in ¿-cell compensation for insulin resistance, which we will compare between groups. We will also examine other potential markers of ¿-cell health. Secondary analyses will examine potential mediators of treatment-specific effects and look for more general mediators of ¿-cell restoration or preservation. The main focus will be on mediators related to obesity. We will also examine fasting glycemia as a potential mediator of ¿-cell restoration or preservation. Clinically, the project will serve as a test of concept for use of gasric banding relatively early in the spectrum of obesity and ¿-cell disease. Biologically, the results will provide crucial information on potential mediators of ¿-cell failure and its arrest or reversa in the context of obesity. Those mediators will guide the development of more effective treatment and monitoring for the ¿-cell disease that causes T2D. We have secured agreement from Allergen to fund clinical care in the gastric band arm, so our approach is cost-effective for NIH. We bring field-leading expertise in ¿-cell biology and preservation in humans. In the end, we believe we can make important new contributions to the field of T2D, as well as to the consortium that will be formed out of this RFA to advance clinical and biological knowledge in that field. PUBLIC HEALTH RELEVANCE (provided by applicant): This project is will compare two leading treatments, one surgical (gastric banding) and one medical (pioglitazone) for their impact on moderately obese Hispanic Americans with prediabetes or mild type 2 diabetes. The results will help to develop more effective approaches to treat and prevent type 2 diabetes and better ways to monitor the success of treatment. NOTE: The following critiques were prepared by the reviewers assigned to this application. These commentaries may not necessarily reflect the position of the reviewers at the close of the group discussion or the final majority opinion of the group, although the reviewers were asked to amend their critiques if their positions changed during the discussion. The resume and other initial sections of the summary statement are the authoritative representations of the final outcome of group discussion. If there is any discrepancy between the peer reviewers' commentaries and the numerical score on the face page of this summary statement, the numerical score should be considered the most accurate representation of the final outcome of the group discussion

描述（由应用程序提供）：我们的研究计划的长期目标是了解导致2型糖尿病（T2D）的渐进性»细胞疾病的原因和开发治疗方法。我们先前的工作和其他人的研究提供了重要的证据，表明肥胖的代谢作用会导致细胞衰竭。改变体内脂肪或其生物学的生活方式改变和药物似乎在某些人中似乎会减慢或停止P细胞检测，但并非大多数。我们假设，胃结束引起的大量体重减轻将比最好的可用药物Pioglitazone在保存或恢复 - 细胞功能方面更有效。我们提出了一项2臂，无盲的研究，以将胃伴侣与吡格列酮进行比较，在24个月的中度肥胖西班牙裔成年人中，具有前或轻度T2D的治疗。主要结果将是对胰岛素抵抗的细胞补偿的变化，我们将在两组之间进行比较。我们还将检查其他潜在标记 - 细胞健康。次要分析将检查特定治疗特异性效应的潜在介体，并寻找更多的通用介质 - 细胞恢复或保存。主要重点将放在与肥胖有关的介体上。我们还将研究禁食性血症作为``细胞恢复或保存''的潜在介体。在临床上，该项目将在肥胖症和细胞疾病的范围内相对较早地使用加油带的概念测试。从生物学上讲，结果将提供有关–细胞失败的潜在介体及其在肥胖症背景下的逮捕或逆转的关键信息。这些介体将指导开发更有效的治疗方法，并监测导致T2D的细胞疾病。我们已经确保了过敏原协议以资助胃臂臂的临床护理，因此我们的方法对NIH具有成本效益。 我们在人类的细胞生物学和保存中带来了领域领先的专业知识。最后，我们认为我们可以为T2D领域做出重要的新贡献，以及将从该RFA中形成的财团，以促进该领域的临床和生物学知识。 公共卫生相关性（由适用提供）：该项目将比较两种领先的治疗方法，一种外科手术（胃结合）和一项医学（吡格列酮）对中度肥胖的西班牙裔美国人患有糖尿病或轻度2型糖尿病的影响。结果将有助于开发更有效的方法来治疗和预防2型糖尿病，并更好地监测治疗成功的方法。 注意：分配给本申请的审阅者准备了以下批判性。这些评论可能不一定反映审稿人在小组讨论结束时的立场或小组的最终多数意见，尽管要求审稿人在讨论期间是否改变了他们的职位，以修改其批判性。摘要声明的简历和其他初始部分是小组讨论最终结果的权威表示。如果同伴审阅者的评论与本摘要声明面对面的数值分数之间存在任何差异，则应将数值分数视为小组讨论最终结果的最准确表示