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: 10000974
• 负责人: BELINDA S LENNERZ
• 金额: $ 19.45万
• 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/10000974
• 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 这项应用的科学目标是探索饮食与新陈代谢和体重之间的联系机制 对照，与1型糖尿病（T1 D）相关。职业发展目标是提高我的 神经影像学、营养学和临床试验的培训--为我走向独立做准备。 尽管技术取得了重大进步，但T1 D的管理仍然不是最佳的， 立即和长期并发症的风险。此外，患有T1 D的个体具有升高的发病率。 饮食失调、超重和代谢综合征，进一步增加慢性病风险。 在这个建议中，我认为控制餐后状态与这些机制有关。 病理生理学挑战。饭后，碳水化合物吸收率和胰岛素作用之间的不匹配 通常会导致高血糖和低血糖的交替期，并伴有潜在的不良反应， 较高的全身胰岛素暴露（例如合成代谢作用、胰岛素抵抗）。概念上有希望的方法 控制这两个问题的方法是调整饮食中的碳水化合物，以减少餐后胰岛素和胰岛素的需求。 在之前的工作中，我证明了高血糖指数（GI）碳水化合物与低血糖指数（GI）碳水化合物相比， 没有糖尿病的人大脑中与成瘾和渴望有关的区域。一项调查研究记录了 在316名儿童和成人中， T1 D食用极低碳水化合物饮食（VLCD）。 在这里，我提出了两个互补的研究：（1）利用神经成像和代谢数据从一个 控制，交叉喂养协议涉及静脉注射胰岛素，我将探讨是否 高GI碳水化合物对饥饿、代谢结果和脑功能的影响是由以下因素介导的： 与血糖、血清胰岛素或两者相关的机制。(2)在为期12周的随机试验中，我将评估 VLCD在治疗T1 D青少年和年轻人中的安全性和初步疗效。作为 根据这些研究的结果，我希望有助于阐明与膳食碳水化合物的类型和数量相关的机制， 脑控制T1 D患者的体重和心血管代谢风险，并提供与以下直接相关的数据： 临床管理。