Beta Cell Restoration through Fat Mitigation

通过减脂恢复β细胞

• 批准号: 8703682
• 负责人: Thomas A Buchanan
• 金额: $ 64.58万
• 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/8703682
• 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; DEXA; Deltastab; Deterioration; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; 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; Pancreas; Pattern; Pharmaceutical Preparations; Pioglitazone; Prediabetes syndrome; Prevention strategy; Primitive foregut structure; 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; 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 beta-cell disease that causes type 2 diabetes (T2D). Our prior work and research by others provides important evidence that metabolic effects of obesity cause beta-cell failure. Lifestyle changes and medications that alter body fat or its biology appear to slow or stop beta-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 beta-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 beta-cell compensation for insulin resistance, which we will compare between groups. We will also examine other potential markers of beta-cell health. Secondary analyses will examine potential mediators of treatment-specific effects and look for more general mediators of beta-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 beta-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 beta-cell disease. Biologically, the results will provide crucial information on potential mediators of beta-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 beta-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 beta-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.

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β细胞疾病的原因和开发治疗方法。我们先前的工作和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β细胞衰竭。生活方式的变化和改变体内脂肪或其生物学的药物似乎在某些人中似乎会减慢或停止β细胞恶化，但并非大多数。我们假设，胃带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β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。主要结果将是胰岛素抵抗的β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β细胞健康的其他潜在标志。次级分析将检查特定治疗特定作用的潜在介体，并寻找更多的β细胞恢复或保存的介体。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β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β细胞疾病的范围内相对早期使用加油带的概念测试。从生物学上讲，结果将提供有关β细胞衰竭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β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β细胞生物学和保存方面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。