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）：我们研究项目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，但不是大多数人。我们假设胃束带引起的体重减轻在保存或恢复细胞功能方面比现有的最佳药物吡格列酮更有效。我们提出了一项两组非盲法研究，比较胃束带与吡格列酮治疗在中度肥胖的西班牙成年人中24个月的前期或轻度T2D。主要结果将是胰岛素抵抗的细胞代偿的变化，我们将在组间进行比较。我们还将研究细胞健康的其他潜在标志。二次分析将检查治疗特异性效果的潜在介质，并寻找更一般的细胞恢复或保存介质。重点将放在与肥胖有关的介质上。我们还将研究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相对早期使用胃束带的概念测试。在生物学上，这些结果将提供关于肥胖背景下细胞衰竭及其抑制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，为胃带臂的临床护理提供资金，因此我们的方法对NIH来说是具有成本效益的。