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.

项目摘要/摘要 囊性纤维化患者（CF）的疗法成功取得了成倍提高的生存率 人口。现在有迫切需要更好地理解如何促进最佳长期健康 这种新老化的人口，这是葡萄糖不耐症和CF相关的高风险 糖尿病（CFRD）。 CFRD在临床和病理生理上与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，有助于CFRD发作的特定因素 进展仍然未知。我们的初步数据暗示饮食是葡萄糖的促成因素 CF的成年人不耐受。体重指数（BMI）与CF生存之间的历史联系已有 鼓励不受限制的高热量高脂饮食的终身处方，以实现特定的BMI目标。 但是，对卡路里和脂肪数量的关注以牺牲饮食质量为代价， 导致过量饮食中添加的糖的广泛消费。典型的高调的影响 糖，高脂CF饮食的葡萄糖耐量尚未进行严格测试。目前，没有足够的 可用于启用循证饮食建议有关碳水化合物质量特定的饮食建议 给有CF的人。这项研究的目的是确定多余的饮食糖作为 CF成年人的葡萄糖不耐症的沉淀因子，并确定潜在的潜在介体。 根据我们的初步数据，我们提出，通常由 患有CF的个体加剧了第一阶段胰岛素分泌和胰岛素抵抗的下降 内脏脂肪组织（增值税）和其他异位脂肪沉积，并通过促进全身性不平衡 氨基硫醇氧化还原朝着氧化状态。我们将使用严格的双盲喂养来检验这一假设 学习。具体而言，我们将确定胰岛素的分泌和灵敏度是否由组合高血糖评估 评估的夹夹和葡萄糖启用精氨酸刺激试验（AIM 1），增值税和其他异位脂肪沉积 通过磁共振成像（AIM 2）和全身性氨基硫醇氧化还原（AIM 3）可以改善八个 通过用欧卡罗式低添加糖，高脂的高脂饮食代替典型的高脂肪CF饮食来数周 饮食。我们还将评估葡萄糖耐受性的变化与增值税的变化与 系统性氧化还原。这项研究符合最近2020 - 2030年NIH营养研究目标的战略计划 使用营养来减轻临床环境中疾病的负担。成功实现我们的目标， 使用严格的饮食干预和金标准的代谢测试和成像，将提供新的 病理生理学洞察饮食在CFRD发展中的作用。这样的数据将告知 饮食方法和其他生活方式或医疗 可能会对CF的个人的健康和生活质量产生持续影响的干预措施。