Impact of Sleep in the Restoring Insulin Secretion (RISE) Study

描述（由申请人提供）：2010年，据估计，2型糖尿病（T2DM）影响了美国近2600万人，占人口的8.3%。2011年1月，美国疾病控制与预防中心发布了令人震惊的数据，显示患有前驱糖尿病的美国成年人数量从2008年的5700万增加到2010年的7900万。前驱糖尿病是一种与发展为T2DM的高风险相关的疾病。在普通人群中，阻塞性睡眠呼吸暂停（OSA）的患病率也随着肥胖的流行而迅速而急剧地增加。事实上，阻塞性睡眠呼吸暂停在T2DM患者中的患病率在58%至86%之间，使其成为T2DM患者中最常见的合并症。据估计，阻塞性睡眠呼吸暂停的患病率在糖尿病前期也非常高。除了肥胖的流行，美国人自我报告的睡眠时间在过去40年里减少了1.5-2小时。在过去的十年中，实验室和流行病学研究已经确定睡眠不足、睡眠碎片化、睡眠质量差和阻塞性睡眠呼吸暂停是假定的T2DM的新危险因素。大量研究已经证实OSA的存在和严重程度与胰岛素抵抗和葡萄糖耐受不良之间存在密切关联，而与肥胖无关。然而，迄今为止，尽管睡眠障碍在糖尿病前期和2型糖尿病中非常普遍，并且对胰岛素的释放和作用有内在的不利影响，但没有一项生活方式和/或药理干预糖尿病前期或2型糖尿病的临床试验考虑到睡眠障碍的作用。目前尚不清楚患有睡眠障碍的个体是否比没有睡眠障碍的个体对糖尿病前期或2型糖尿病的药物治疗更有抵抗力。本研究旨在测试短期强化药物干预对维持或增强β细胞功能的影响，从而预防或延缓T2DM的发展。拟议辅助研究的总体目标是：1)确定睡眠数量和质量的定量测量是否可以预测ss-细胞功能（胰岛素分泌）和胰岛素敏感性的基线测量，2)评估睡眠障碍的存在和严重程度是否影响ss-细胞对旨在保持和/或恢复胰岛素分泌的药物干预的反应。该提案将利用RISE研究对250多名参与者在基线和随机化干预后的ss细胞功能和胰岛素敏感性的独特详细量化。在随机化之前，参与者将进行一周的家庭手腕活动描记和一晚的实验室多导睡眠描记（PSG）。我们假设，在糖尿病前期或早期T2DM患者中，习惯性睡眠时间短、习惯性睡眠质量差、OSA的存在和严重程度以及低水平SWA均与ss细胞功能降低和胰岛素敏感性降低有关。我们还假设，这些睡眠障碍中的每一种都会降低旨在保持和恢复ss细胞功能的药物干预的有效性。

DESCRIPTION (provided by applicant): In 2010, it was estimated that type 2 diabetes mellitus (T2DM) affects nearly 26 million individuals in the U.S. or 8.3% of the population. The US Centers for Disease Control and Prevention released alarming figures in January 2011 showing that the number of American adults with prediabetes, a condition associated with a high risk of developing frank T2DM, had increased from 57 million in 2008 to 79 million in 2010. The prevalence of obstructive sleep apnea (OSA) in the general population has also increased rapidly and dramatically, in parallel with the epidemic of obesity. In fact, the prevalence of OSA in patients with T2DM ranges between 58 to 86% making it the most common comorbidity in T2DM. It has been estimated that the prevalence of OSA is also very high in prediabetes. In addition to the obesity epidemic, self-reported sleep duration in Americans has decreased by 1.5-2 h over the last few 4 decades. Over the past decade, both laboratory and epidemiologic studies have identified insufficient sleep, sleep fragmentation, poor sleep quality and OSA, as putative novel risk factors for T2DM. Numerous studies have established a robust association between the presence and severity of OSA with both insulin resistance and glucose intolerance, independent of adiposity. However, to date, not a single clinical trial of lifestyle and/or pharmacological interventions for prediabetes or T2DM has taken into account the role of sleep disturbances despite their very high prevalence in prediabetes and T2DM and their intrinsic adverse impact on insulin release and action. It is not known whether individuals suffering from sleep disturbances are more resistant than those without sleep disruption to pharmacological treatment for prediabetes or T2DM. The parent RISE Study was designed to test the impact of intensive short-term pharmacological interventions to preserve or enhance beta cell function to prevent or delay the development of frank T2DM. The overall goals of the proposed ancillary study are: 1) To determine if quantitative measures of sleep quantity and quality are predictors of baseline measures of ss-cell function (insulin secretion) and insulin sensitivity, and 2) To assess whether the presence and severity of sleep disturbances impact the ss-cell response to pharmacological interventions designed to preserve and/or restore insulin secretion. This proposal will capitalize on the RISE Study's uniquely detailed quantification of ss-cell function and insulin sensitivity in more than 250 participants both at baseline and after randomization to an intervention. Prior to randomization, participants will undergo one week of home wrist actigraphy and one night of in-laboratory polysomnography (PSG). We hypothesize that in subjects with prediabetes or early T2DM, habitual short sleep duration, poor habitual sleep quality, presence and severity of OSA and low levels of SWA are each associated with reduced ss- cell function and decreased insulin sensitivity. We also hypothesize that each of these sleep disturbances will decrease the effectiveness of pharmacological interventions intended to preserve and restore ss-cell function.