Morning Light Treatment at Home to Improve Glucose Metabolism in People at Increased Risk for Type 2 Diabetes

 描述（由申请人提供）：超过2100万美国成年人（约占人口的10%）患有2型糖尿病（T2 DM），另有2900万人患有前驱糖尿病。针对前驱糖尿病以预防T2 DM的发展将对数百万人的健康产生重大影响。迫切需要新的干预措施来实现这一目标。对于这项R21探索/开发资助，我们建议将晨光治疗作为一种新型，安全，非药物干预来改善前驱糖尿病患者的葡萄糖代谢。这项研究的基础是来自实验室和人群研究的最新证据，表明昼夜节律失调与T2 DM风险增加和血糖控制不良独立相关。我们也有试验数据表明，晚的昼夜节律时间（晚昏暗的光褪黑激素发作，DLMO）与更高的空腹血糖水平显着相关。在这里，我们建议将这些发现转化为一种新的行为干预，晨光治疗，以改善糖尿病前期患者的葡萄糖代谢。迄今为止，晨光治疗已被证明可以减少体脂，但葡萄糖代谢仍有待研究。我们将测试一种新型头戴式光设备（Re-Timer（r）），该设备通过允许患者在光治疗期间走动来减轻受试者负担。我们包括试点数据，证明我们有能力衡量光治疗的依从性。我们将招募34名受试者（17名男性，17名女性，年龄40-65岁），他们将：（1）肥胖（BMI>30 kg/m2），（2）患有前驱糖尿病（HbA 1c 5.7%至<6.5%），（3）具有显著的昼夜节律失调（“社会时差”≥ 2 h），以及（4）没有中度至重度阻塞性睡眠呼吸暂停（呼吸暂停低通气指数<15）。我们将在家中测量基线睡眠（腕动计）1周，然后进行实验室检查以测量昼夜节律（DLMO），并在早晨进行3小时（8样本）口服葡萄糖耐量试验（OGTT）。然后将受试者随机分配至为期4周的每日1小时晨间光照治疗，使用活性或安慰剂重新计时器（r）。4周光照治疗后，将重复实验室检查，以重新评估DLMO和OGTT。具体目标1是确定活性与安慰剂晨光治疗对糖尿病前期个体葡萄糖代谢的影响。具体目标2是确定昼夜节律相位提前与葡萄糖代谢改善相关的程度。在探索性目的中，我们将检查其他可能的介质（体脂，活动，总热量摄入， 睡眠片段），这也可以解释葡萄糖代谢的变化。晨光治疗已经被几个患者群体使用，并且光设备已经在商业上可用。因此，改善葡萄糖代谢的晨光治疗很容易转化为临床实践，作为一种新型、安全、非药物干预措施，可以添加到其他生活方式干预措施中。这项试点研究是朝着发展迈出的重要的第一步 一项更大规模的随机临床试验，研究晨光治疗改善葡萄糖代谢。

 DESCRIPTION (provided by applicant): Over 21 million US adults (~10% of the population) have type 2 diabetes mellitus (T2DM) and another 29 million have prediabetes. Targeting prediabetes to prevent the development of T2DM would have a substantial impact on the health of millions. Novel interventions to accomplish this are urgently needed. For this R21 Exploratory/Development grant, we propose to examine morning light treatment as a novel, safe, non- pharmacological intervention to improve glucose metabolism in people with prediabetes. The basis for this research is the recent evidence from both laboratory and population studies indicating that circadian misalignment is independently associated with increased risk for T2DM and poorer glucose control. We also have pilot data indicating later circadian timing (later dim light melatonin onset, DLMO) is significantly associated with a higher fasting glucose level. Here we propose to translate these findings into a novel behavioral intervention, morning light treatment, to improve glucose metabolism in people with prediabetes. To date, morning light treatment has been shown to reduce body fat, but glucose metabolism remains to be investigated. We will test a novel head worn light device (Re-Timer(r)) that reduces subject burden by allowing people to be ambulatory during light treatment. We include pilot data demonstrating our ability to measure compliance to light treatment. We will enroll 34 subjects (17 male, 17 female, ages 40-65 years), who will: (1) be obese (BMI>30 kg/m2), (2) have prediabetes (HbA1c 5.7% to <6.5%), (3) have significant circadian misalignment ("social jet lag" ≥ 2 h), and (4) be free of moderate to severe obstructive sleep apnea (apnea- hypopnea index<15). We will measure baseline sleep at home (wrist actigraphy) for 1 week, followed by a laboratory session to measure circadian timing (DLMO) and conduct a 3-hour (8-sample) oral glucose tolerance test (OGTT) in the morning. Subjects will then be randomized to 4 weeks of a 1 hour daily morning light treatment using either an active or placebo Re-timer(r). After 4 weeks of light treatment, the laboratory session will be repeated to reassess DLMO and OGTT. Specific Aim 1 is to determine the effect of active versus placebo morning light treatment on glucose metabolism in individuals with prediabetes. Specific Aim 2 is to determine the extent to which circadian phase advances are related to improvements in glucose metabolism. In an Exploratory Aim we will examine other possible mediators (body fat, activity, total caloric intake, sleep fragmentation) that may also explain changes in glucose metabolism. Morning light treatment is already used by several patient groups and the light device is already commercially available. Thus a morning light treatment to improve glucose metabolism would readily translate into clinical practice, as a novel, safe, non-pharmacological intervention that could be added to other lifestyle interventions. This pilot study is the important first step towards the development of a larger randomized clinical trial of morning light treatment to improve glucose metabolism.