Effects of dietary carbohydrate on postprandial metabolism, brain function and type 1 diabetes control

膳食碳水化合物对餐后代谢、脑功能和 1 型糖尿病控制的影响

• 批准号: 10436559
• 负责人: BELINDA S LENNERZ
• 金额: $ 9.72万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-07 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436559
• 关键词: Acute; Adolescent; Adolescent and Young Adult; Adult; Adverse effects; Algorithms; Analysis of Variance; Area; Behavioral; Blood; Blood Glucose; Body Weight; Body Weight decreased; Brain; Carbohydrates; Case Series; Child; Chronic; Chronic Disease; Clinical Management; Clinical Trials; Complication; Conduct Clinical Trials; Consumption; Crossover Design; Data; Diabetes Mellitus; Diabetic Diet; Diet; Dietary Carbohydrates; Dose; Eating; Female; Food; Functional Magnetic Resonance Imaging; Funding; Glucose; Glycemic Index; Glycosylated hemoglobin A; Goals; Health; Hepatic; Hunger; Hyperinsulinism; Hypoglycemia; Individual; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Intake; Intervention; Intervention Studies; Intravenous; Learning; Link; Lipids; Macronutrients Nutrition; Mediating; Medical; Metabolic; Metabolic Control; Metabolic syndrome; Metabolism; Methods; Modality; Modification; Nonesterified Fatty Acids; Nucleus Accumbens; Nutritional Biochemistry; Nutritional Study; Outcome; Outcome Measure; Overweight; Participant; Peripheral; Physicians; Physiological; Physiology; Positioning Attribute; Postprandial Period; Preparation; Process; Protocols documentation; Quality of life; Randomized Controlled Trials; Regimen; Regulation; Research; Research Personnel; Rest; Risk; SECTM1 gene; Safety; Scientist; Serum; Spin Labels; Surveys; Techniques; Testing; Tissues; Training; Weight maintenance regimen; Work; Writing; absorption; addiction; aged; analog; career development; clinically significant; craving; design; diabetes control; diabetes management; dietary restriction; disorder risk; experience; feeding; glucose monitor; glycemic control; improved; increased appetite; insulin signaling; male; mind control; neuroimaging; novel; nutrition; prevent; randomized trial; skills; standard of care; training opportunity; weight maintenance; work-study

PROJECT SUMMARY The scientific goal of this application is to explore the mechanisms linking diet to metabolism and body weight control, with relevance to type one diabetes mellitus (T1D). The career development goal is to advance my training in neuroimaging, nutrition, and clinical trial conduct - in preparation for my transition to independence. Despite major technological advances, management of T1D remains suboptimal, putting millions of people at risk for immediate and long-term complications. Moreover, individuals with T1D have elevated rates of dysregulated eating, overweight, and metabolic syndrome, further contributing to chronic disease risk. In this proposal, I consider control of the postprandial state as mechanistically related to each of these pathophysiological challenges. After meals, a mismatch between carbohydrate absorption rate and insulin action typically leads to alternating periods of hyper- and hypoglycemia, compounded by potential adverse effects of higher systemic insulin exposure (e.g. anabolic effects, insulin resistance). A conceptually promising approach to control both problems is dietary carbohydrate modification to reduce postprandial glycemia and insulin needs. In prior work, I demonstrated that high- vs low- glycemic index (GI) carbohydrate increased hunger and activation of brain areas involved in addiction and craving in individuals without diabetes. A survey study documented exceptional glycemic control (HbA1c 5.7% and low acute complication rate) among 316 children and adults with T1D consuming a very-low-carbohydrate diet (VLCD). Here I propose two complementary studies: (1) Leveraging neuroimaging and metabolic data obtained from a controlled, cross-over feeding protocol involving intravenous insulin administration, I will explore whether the effects of high GI carbohydrates on hunger, metabolic outcomes, and brain function are mediated by mechanisms related to blood glucose, serum insulin or both. (2) In a 12-week randomized trial, I will assess the safety and preliminary efficacy of a VLCD in the management of adolescents and young adults with T1D. As a result of these studies, I hope to help elucidate mechanisms relating type and amount of dietary carbohydrate to glycemia, brain control of body weight and cardio metabolic risk in T1D, and provide data of direct relevance to the clinical management.

项目摘要 该应用的科学目标是探索将饮食与新陈代谢和体重联系起来的机制 控制，与一型糖尿病（T1D）相关。职业发展目标是促进我的 在神经影像，营养和临床试验中进行培训 - 为我向独立过渡做准备。 尽管有重大的技术进步，但T1D的管理仍然是最佳的，使数百万人处于 立即和长期并发症的风险。此外，具有T1D的人的率较高 饮食，超重和代谢综合征失调，进一步导致慢性疾病风险。 在此提案中，我认为对餐后状态的控制是与每一种 病理生理挑战。饭后，碳水化合物吸收率与胰岛素作用之间的不匹配 通常导致高血糖症和低血糖的交替时期，并由 较高的全身胰岛素暴露（例如合成代谢作用，胰岛素抵抗）。一种概念上有前途的方法 控制这两个问题的是饮食中的碳水化合物修饰，以减少餐后血糖和胰岛素需求。 在先前的工作中，我证明高血糖指数（GI）碳水化合物增加了饥饿和激活 在没有糖尿病的个体中涉及成瘾和渴望的大脑区域。一项调查研究记录了 316名患有 T1D消耗非常低的碳水化合物饮食（VLCD）。 在这里，我提出了两项​​互补研究：（1）利用从A获得的神经影像学和代谢数据 涉及静脉胰岛素给药的受控的，交叉的喂养方案，我将探讨是否探讨 高胃肠道碳水化合物对饥饿，代谢结果和大脑功能的影响是由 与血糖，血清胰岛素或两者相关的机制。 （2）在一项为期12周的随机试验中，我将评估 VLCD在T1D的青少年和年轻人的管理中的安全性和初步功效。作为 这些研究的结果，我希望有助于阐明与饮食碳水化合物类型和数量相关的机制 T1D中的血糖，大脑控制体重和有氧代谢风险，并提供与直接相关的数据 临床管理。