Personalizing Sleep Interventions to Prevent Type 2 Diabetes in Community Dwelling Adults with Pre-Diabetes

项目概要 饮食和运动干预在预防和延缓 T2D 发病方面取得了巨大进步：好处 对某些人的作用超过了药物干预。然而，强度较低、强度较大的反应会有所不同 负担得起的干预措施和随着时间的推移效益逐渐减弱是重大限制。确定额外的 需要可改变的因素来扩大饮食和运动之外的干预选择，以达到 迄今为止的耐药群体并维持代谢益处。一种可行的选择是改善睡眠。多个 睡眠维度与人类 T2D 风险和血糖控制不良独立相关 与 T2D。据报道，在一个小型社区中，每日睡眠延长时间改善了胰岛素敏感性 研究（N = 16），以及为期 2 天的基于实验室的睡眠延长研究，使用个性化的“追赶”睡眠 对健康成年人的干预（N = 19）。受到小样本量、受控实验室条件和 排除 T2D 风险最大的人群后，睡眠在降低 T2D 风险中的作用仍不确定。安 调整睡眠干预措施的一个重要但尚未解答的问题是，是否应该定期调整睡眠时间 优先。鉴于不规律的睡眠-觉醒时间普遍存在，确定代谢益处或 这种睡眠习惯的负担至关重要。 K99/R00 奖项中提议的项目是朝着 独立于将昼夜节律和新陈代谢与时间治疗联系起来的研究计划 降低 2 型糖尿病 (T2D) 风险的干预措施。 研究：K99 阶段提出的研究将利用现有数据集来量化 不规律的睡眠时间对糖尿病、糖尿病前期和血糖正常患者的血糖调节的影响。这个 将阐明个体对不规则睡眠时间的适应能力或脆弱性的差异。小学 结果测量将是血红蛋白 A1c（对于糖尿病和糖尿病前期患者）或胰岛素抵抗 （对于血糖正常的人）。 R00 阶段提出的研究将测试每日服用的效果 睡眠延长干预与习惯性睡眠模式对血糖≥ 140 mg/dL 的时间百分比的影响 （每组 n = 75 名）睡眠受限的社区居民患有糖尿病前期的成年人。穿戴式传感器 将使用技术（连续血糖监测和加速测量）。这项研究将告知人们—— 改善血糖反应的特定睡眠干预措施，从而为糖尿病前期状态提供治疗。 培训：为了实现总体职业目标，培训计划将建立在候选人的背景之上 通过为她提供设计睡眠干预措施、可穿戴传感器技术方面的深入培训来治疗糖尿病 （特别是连续血糖监测）以及大量实时数据的分析。本次培训 还将包括提高她的写作和展示科学发现的技能，以及 成为科学界的领导者。将采用多种方法来实现这些目标 包括正式的课程作业和结构化的一对一指导。

PROJECT SUMMARY Diet and exercise interventions have made great strides in preventing and delaying T2D onset: benefits that surpass pharmacological interventions in some persons. Yet, variable responses from less intense, more affordable interventions and waning benefits over time are significant limitations. Identifying additional modifiable factors that can expand intervention options, beyond diet and exercise, are needed to reach heretofore resistant groups and to sustain metabolic benefits. One viable option is improving sleep. Multiple dimensions of sleep have been independently associated with T2D risk and poor glucose control in persons with T2D. Improved insulin sensitivity has been reported in a small community based daily sleep extension study (N= 16), as well as in a 2-day lab based sleep extension study using a personalized “catch up” sleep intervention in healthy adults (N = 19,). Limited by small sample sizes, controlled lab conditions, and the exclusion of persons at greatest risk for T2D, the role of sleep in mitigating T2D risk remains uncertain. An important but unanswered question for tailoring sleep interventions is whether regular sleep timing should be prioritized. Given that irregular sleep-wake timing is widely prevalent, identifying the metabolic benefits or burdens of this sleep habit is critical. The proposed project in this K99/R00 award is a step toward independence in a program of research bridging circadian rhythms and metabolism to chrono-therapeutic interventions that mitigate type 2 diabetes (T2D) risk. Research: The study proposed in the K99 phase will leverage an existing data set to quantify the effects of irregular sleep timing on glucose regulation in persons with diabetes, prediabetes, and normoglycemia. This will elucidate individual differences in resiliency against or vulnerability to irregular sleep timing. Primary outcome measures will be hemoglobin A1c (for persons with diabetes and prediabetes) or insulin resistance (for persons with normoglycemia). The study proposed during the R00 phase will test the effects of a daily sleep extension intervention versus habitual sleep patterns on the percentage of time glucose is  140 mg/dL (n = 75 per group) in sleep restricted community-dwelling adults with pre-diabetes. Wearable sensor technologies (continuous glucose monitoring and accelerometry) will be used. This study will inform person- specific sleep interventions that improve glycemic responses, thus providing treatment for the prediabetic state. Training: To achieve overall career goals, the training plan will build upon the candidate's background in diabetes by affording her in-depth training in designing sleep interventions, wearable sensor technologies (specifically continuous glucose monitoring), and the analysis of large amounts of real time data. This training will also incorporate advancing her skills in writing and presenting scientific findings, as well as the skills to become a leader in the scientific community. A variety of approaches will be used to achieve these goals including formal coursework and structured one-on-one mentorship.