Impact of Meal Timing on Glycemic Profiles in Adolescents with Type 2 Diabetes

候选人：Alaina Vidmar是一名儿科临床科学家，专门研究青少年肥胖症的治疗 2型糖尿病（T2 D）这项拟议的研究将重点调查是否有时间限制的饮食（TLE：8小时 进食/禁食16小时）可降低血糖波动，延缓β细胞功能障碍， 与延长进食时间（12小时以上）相比，减少了身体脂肪量。K23奖将为她提供 在临床试验设计和先进的统计方法，儿科营养和身体的高级培训 成分测量和葡萄糖监测技术，所有这些都是她参加比赛所必需的 R 01独立融资。研究背景：初步证据，主要是在成人中，已经表明TLE 降低体重和脂肪量，改善胰岛素敏感性，减少肝脏脂肪堆积，安全 与长时间进食窗口相比，风险最小，对日常功能没有负面影响， 生活方式行为。1-12由于其简单性，TLE可能是青少年更可行的方法 而不是其他的热量限制方案。我们的初步数据支持TLE的可行性、可接受性和安全性， 13 -15然而，迄今为止还没有试验研究TLE的影响。 血糖控制和身体组成的影响。我们假设TLE会减少 血糖波动，改善β细胞功能，并减少T2 D青少年的体脂量， 延长进食时间100例T2 D青少年（年龄14-21岁），血红蛋白A1 c （HbA 1c）<9%，并接受二甲双胍单药治疗。所有受试者将被随机分配至 两个进餐时间表将遵循12周：（1）对照：>12小时进食或（2）TLE。我们将研究 TLE与对照组在3个特定目标上的效果：（1）对血糖控制的效果，以时间百分比测量 范围内（从持续葡萄糖监测数据中获取）、血红蛋白A1 c和β细胞功能（平均变化 混合餐耐量试验后胰岛素生成指数）;（2）对身体组成和肝脏脂肪的影响（DEXA 和磁共振成像）;和（3）对睡眠、身体活动和饮食摄入的影响。职业生涯 发展：Vidmar博士拥有丰富的学术研究环境，是世界上最大的儿科研究机构之一。 该国的T2 D人群，她所在机构的支持，以及由以下人员组成的一流指导委员会（1） 博士Goran，儿科营养科学家，（2）Raymond博士，糖尿病专家 技术，（3）统计学家Ramon Durazo-Arvizu博士，（4）临床生物信息学专家Espinoza博士， 以及（5）Salvy博士，行为和临床心理学家，在TLE实施方面具有专业知识。两人共同- 主要导师，Goran博士和Raymond博士将负责指导Vidmar博士实现里程碑 向独立过渡。总之，这项建议满足了寻找有效的 饮食干预治疗T2 D青少年，并为Vidmar博士提供了一个强大的培训平台， 和结构化的指导路径，以实现R 01级竞争应用程序。

CANDIDATE: Alaina Vidmar is a pediatric clinical scientist specializing in treatment of adolescents with obesity and type 2 diabetes (T2D). The proposed study will focus on investigating if time-limited eating (TLE: 8-hour eating/16-hour fasting) in adolescents with T2D reduces glycemic excursions, delays β-cell dysfunction, and reduces body fat mass compared to prolonged eating period (12+hours). This K23 Award will provide her with advanced training in clinical trial design and advanced statistical methods, pediatric nutrition and body composition measurement, and glucose monitoring technology, all of which are required for her to compete for independent R01 funding. RESEARCH CONTEXT: Preliminary evidence, mostly in adults, has shown that TLE reduces body weight and fat mass, improves insulin sensitivity, reduces hepatic fat accumulation, and is safe with minimal risk when compared to prolonged eating windows and has no negative effect on daily function or lifestyle behaviors. 1–12 Because of its simplicity, TLE may represent a more feasible approach for adolescents than other caloric restriction regimens. Our preliminary data support TLE feasibility, acceptability, and safety in adolescents with obesity, with and without diabetes.13–15 However, no trial to date has studied the effects of TLE on glycemic control and body composition in adolescents with T2D. We hypothesize that TLE will reduce glycemic excursions, improve β-cell function, and reduce body fat mass in adolescents with T2D when compared to prolonged eating periods. One-hundred adolescents with T2D (aged 14-21 years), with a hemoglobin A1c (HbA1c) < 9%, and on Metformin monotherapy, will be recruited. All participants will be randomized to one of two meal-timing schedules to be followed for 12 weeks: (1) Control: >12-hour eating or (2) TLE. We will examine the effects of TLE versus control in 3 specific aims: (1) Effects on glucose control as measured by percent time in range (captured from continuous glucose monitoring data), Hemoglobin A1c, and β-cell function (mean change in insulinogenic index after a mixed meal tolerance test); (2) Effects on body composition and liver fat (DEXA and magnetic resonance imaging); and (3) Effects on sleep, physical activity, and dietary intake. CAREER DEVELOPMENT: Dr. Vidmar has access to a rich academic research environment, one of the largest pediatric T2D populations in the country, the support of her institution, and a stellar mentoring committee consisting of (1) Dr. Goran, a pediatric nutritional scientist, (2) Dr. Raymond, a physician-scientist with expertise in diabetes technology, (3) Dr. Ramon Durazo-Arvizu, a statistician, (4) Dr. Espinoza, an expert in clinical bioinformatics, and (5) Dr. Salvy, a behavioral and clinical psychologist with expertise in TLE implementation. The two co- primary mentors, Drs. Goran and Raymond will be responsible for guiding Dr. Vidmar in achieving the milestones towards transition to independence. In summary, this proposal meets a critical need for finding an effective dietary intervention for treatment of adolescents with T2D and provides Dr. Vidmar with a robust training platform, and structured mentoring path towards an R01-level competitive application.