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（由申请人提供）：我们研究计划的长期目标是了解导致 2 型糖尿病 (T2D) 的进行性 ¿ 细胞疾病的原因并开发治疗方法。我们之前的工作和其他人的研究提供了重要的证据，证明肥胖的代谢影响会导致 细胞衰竭。生活方式的改变和改变体脂或其生物学特性的药物似乎可以减缓或阻止某些人的 P 细胞退化，但对大多数人来说却不是这样。我们假设，在保留或恢复 细胞功能方面，胃束带引起的显着体重减轻将比现有的最佳药物吡格列酮更有效。我们提出了一项 2 组、非盲研究，对患有前期或轻度 T2D 的中度肥胖西班牙裔成年人进行 24 个月内胃束带治疗与吡格列酮治疗的比较。主要结果将是胰岛素抵抗的细胞补偿的变化，我们将在各组之间进行比较。我们还将检查其他潜在的细胞健康标志。二次分析将检查治疗特异性效应的潜在介质，并寻找更一般的细胞恢复或保存介质。主要关注点是与肥胖相关的介质。我们还将检查空腹血糖作为细胞恢复或保存的潜在介质。在临床上，该项目将作为在肥胖和细胞疾病谱系中较早使用胃带的概念测试。从生物学角度来看，这些结果将提供有关肥胖背景下 β 细胞衰竭及其停滞或逆转的潜在介质的重要信息。这些介质将指导开发更有效的治疗和监测导致 T2D 的 细胞疾病。我们已获得 Allergen 的同意，为胃束带臂的临床护理提供资金，因此我们的方法对于 NIH 来说是具有成本效益的。 我们带来了人类细胞生物学和保存领域领先的专业知识。最后，我们相信我们能够为 T2D 领域以及由本次 RFA 组成的联盟做出重要的新贡献，以推进该领域的临床和生物学知识。 公共健康相关性（由申请人提供）：该项目将比较两种主要治疗方法，一种是手术治疗（胃束带术）和一种药物治疗（吡格列酮）对患有糖尿病前期或轻度 2 型糖尿病的中度肥胖西班牙裔美国人的影响。研究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，以及更好的方法来监测治疗的成功。 注：以下评论是由分配给此应用程序的审阅者准备的。这些评论可能不一定反映小组讨论结束时审稿人的立场或小组的最终多数意见，尽管审稿人被要求在讨论期间如果立场发生变化则修改他们的批评。简历和总结陈述的其他开头部分是小组讨论最终结果的权威代表。如果同行评审员的评论与本摘要声明首页上的数字分数之间存在任何差异，则数字分数应被视为小组讨论最终结果的最准确表示