Beta Cell Restoration through Fat Mitigation

通过减脂恢复β细胞

• 批准号: 8535244
• 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/8535244
• 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.

描述（由申请人提供）：我们研究计划的长期目标是了解进行性癌症的原因并开发治疗方法 ¿ -导致 2 型糖尿病 (T2D) 的细胞疾病。我们之前的工作和其他人的研究提供了重要证据，证明肥胖的代谢效应会导致 ¿改变生活方式和改变身体脂肪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，但不是大多数人，我们认为胃束带术引起的显着减肥比现有的最佳方法更有效。药物，吡格列酮，保存或恢复 ¿我们提出了一项 2 组、非盲法研究，对患有前期或轻度 T2D 的中度肥胖西班牙裔成人进行 24 个月的胃束带治疗与吡格列酮治疗的比较。 -胰岛素抵抗的细胞补偿，我们将在各组之间进行比较，我们还将检查其他潜在的标记物。 -细胞健康状况的二次分析将检查治疗特异性效应的潜在调节因素，并寻找更一般的调节因素。 -细胞恢复或保存。我们还将研究空腹血糖作为潜在的调节因素。 -细胞恢复或保存在临床上，该项目将作为在肥胖症谱系中较早使用胃带的概念测试。从生物学角度来看，结果将提供有关 ¿ 潜在介质的重要信息。 -肥胖背景下的细胞衰竭及其停滞或逆转，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 来说具有成本效益。 我们带来领域领先的专业知识 ¿最后，我们相信我们可以为 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。