A Dietary Intervention to Improve Glucose Tolerance in Adults with Cystic Fibrosis

改善囊性纤维化成人葡萄糖耐量的饮食干预

• 批准号: 10504605
• 负责人: Jessica Alejandra Alvarez
• 金额: $ 64.15万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10504605
• 关键词: Achievement; Address; Adipose tissue; Adult; Age; Area; Arginine; Beta Cell; Body fat; Body mass index; Calories; Carbohydrates; Caring; Cell physiology; Clinical; Clinical Trials Cooperative Group; Closure by clamp; Communities; Consumption; Control Groups; Cysteine; Cystic Fibrosis; Cystine; Data; Deposition; Development; Diabetes Mellitus; Diet; Diet Modification; Dietary Intervention; Dietary Sugars; Disulfides; Double-Blind Method; Endocrine; Equilibrium; Fatty acid glycerol esters; Food; General Population; Genetic Diseases; Glucose; Glucose Intolerance; Goals; Gold; Guidelines; Health; High Fat Diet; Homeostasis; Hyperglycemia; Image; Impairment; Individual; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Intervention; Knowledge; Life; Life Style; Link; Liver; Macronutrients Nutrition; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Medical; Metabolic; Metabolic Pathway; Modification; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Nutritional Study; Outcome; Oxidation-Reduction; Oxidative Stress; Oxides; Pancreas; Participant; Pathogenesis; Pathway interactions; Persons; Pharmacotherapy; Phase; Plasma; Population; Precipitating Factors; Prediabetes syndrome; Prevention; Quality of life; Randomized; Recommendation; Research; Research Priority; Resolution; Role; Strategic Planning; Testing; Thigh structure; Time; Translating; United States National Institutes of Health; Visceral; Visceral fat; Weight Gain; Work; aging population; aminothiol; base; body system; burden of illness; clinical care; cystic fibrosis patients; cystic fibrosis related diabetes; design; diabetes risk; dietary; dietary approach; dietary control; dietary excess; evidence base; extracellular; feeding; glucose tolerance; high risk; improved; insight; insulin secretion; insulin sensitivity; liquid chromatography mass spectrometry; metabolomics; novel; nutrition; prevent; recessive genetic trait; spectroscopic imaging; standard of care; success; sugar

PROJECT SUMMARY/ABSTRACT Successes in therapies for individuals with cystic fibrosis (CF) have exponentially improved survival in this population. There is now a critical need for better understanding of how to promote optimal long-term health in this newly aging population, which is at high risk for development of glucose intolerance and CF-related diabetes (CFRD). CFRD is clinically and pathophysiologically distinct from type 1 and type 2 diabetes mellitus, and it drastically impairs quality of life and survival. Unfortunately, specific factors contributing to CFRD onset and progression remain unknown. Our preliminary data implicate diet as a precipitating factor in glucose intolerance in adults with CF. Historical links between body mass index (BMI) and survival in CF have encouraged the life-long prescription of an unrestricted high-calorie, high-fat diet to meet specific BMI goals. However, the focus on the quantity of calories and fat has come at the expense of the quality of the diet, resulting in the widespread consumption of excess dietary added sugars. The impact of the typical high-added sugar, high-fat CF diet on glucose tolerance has not been rigorously tested. Currently, there is insufficient research available to enable evidence-based dietary recommendations regarding carbohydrate quality specific to individuals with CF. The purpose of this study is to determine the extent that excess dietary sugars serve as a precipitating factor in glucose intolerance in adults with CF and to identify potential underlying mediators. Based on our preliminary data, we propose that the high-added sugar diets that are typically consumed by individuals with CF exacerbate a decline in first-phase insulin secretion and insulin resistance by enhancing visceral adipose tissue (VAT) and other ectopic fat deposition and by promoting an imbalance in systemic aminothiol redox towards an oxidized state. We will test this hypothesis using a rigorous, double-blind feeding study. Specifically, we will determine if insulin secretion and sensitivity assessed by a combined hyperglycemic clamp and glucose-potentiated arginine stimulation test (Aim 1), VAT and other ectopic fat deposition assessed by magnetic resonance imaging (Aim 2), and systemic aminothiol redox (Aim 3) can be improved over eight weeks by replacing the typical high-added sugar, high-fat CF diet with a eucaloric low-added sugar, high-fat diet. We will also assess relationships between the changes in glucose tolerance and changes in VAT and systemic redox. This study is in line with the recent 2020-2030 Strategic Plan for NIH Nutrition Research goal of using nutrition to reduce the burden of disease in clinical settings. Successful achievement of our aims, using a rigorous dietary intervention with gold-standard metabolic testing and imaging, will deliver new pathophysiological insight into the role of diet towards the development of CFRD. Such data will inform evidence-based design, with mechanistic support, of dietary approaches and other lifestyle or medical interventions that may have a sustained impact on the health and quality of life of individuals living with CF.

项目概要/摘要 囊性纤维化 (CF) 患者治疗的成功极大地提高了患者的生存率 人口。现在迫切需要更好地了解如何促进最佳长期健康 这个新近老龄化的人群，发生葡萄糖不耐受和 CF 相关疾病的风险很高 糖尿病（CFRD）。 CFRD 在临床和病理生理学上与 1 型和 2 型糖尿病不同， 它极大地损害了生活质量和生存。不幸的是，导致 CFRD 发生的具体因素 且进展仍未知。我们的初步数据表明饮食是葡萄糖的诱发因素 成人 CF 患者不耐受。体重指数 (BMI) 与 CF 生存率之间的历史联系 鼓励终身实行无限制的高热量、高脂肪饮食，以满足特定的体重指数目标。 然而，对卡路里和脂肪数量的关注却以牺牲饮食质量为代价， 导致人们普遍食用过量的膳食添加糖。典型高添加的影响 糖、高脂肪CF饮食对糖耐量的影响尚未经过严格测试。目前，资源不足 现有研究可提供有关碳水化合物质量特定的基于证据的饮食建议 患有 CF 的个人。本研究的目的是确定过量膳食糖在多大程度上发挥作用 成人 CF 患者葡萄糖不耐受的诱发因素，并确定潜在的潜在介质。 根据我们的初步数据，我们建议通常食用的高添加糖饮食 患有 CF 的个体通过增强胰岛素抵抗来加剧第一相胰岛素分泌和胰岛素抵抗的下降 内脏脂肪组织（VAT）和其他异位脂肪沉积，并通过促进全身不平衡 氨基硫醇氧化还原成氧化态。我们将使用严格的双盲喂养来测试这个假设 学习。具体来说，我们将确定是否通过联合高血糖评估胰岛素分泌和敏感性 钳夹和葡萄糖强化精氨酸刺激试验（目标 1）、VAT 和其他异位脂肪沉积评估 通过磁共振成像（目标 2），全身性氨基硫醇氧化还原（目标 3）可以改善超过 8 个 用低添加糖、高脂肪的无热量饮食替代典型的高添加糖、高脂肪 CF 饮食，需要几周的时间 饮食。我们还将评估葡萄糖耐量变化与增值税和增值税变化之间的关系 系统性氧化还原。这项研究符合最近的 NIH 营养研究目标 2020-2030 年战略计划 在临床环境中利用营养来减轻疾病负担。成功实现我们的目标， 使用严格的饮食干预以及金标准代谢测试和成像，将提供新的 饮食对 CFRD 发展的作用的病理生理学见解。此类数据将告知 饮食方法和其他生活方式或医学的循证设计，具有机械支持 可能对 CF 患者的健康和生活质量产生持续影响的干预措施。