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（T2 DM）影响美国近2600万人或8.3%的人口。美国疾病控制和预防中心在2011年1月发布了令人震惊的数据，显示美国成年人患有前驱糖尿病的人数从2008年的5700万增加到2010年的7900万。阻塞性睡眠呼吸暂停（OSA）在普通人群中的患病率也迅速而显著地增加，与肥胖症的流行并行。事实上，OSA在T2 DM患者中的患病率在58%至86%之间，使其成为T2 DM中最常见的合并症。据估计，OSA的患病率在前驱糖尿病中也非常高。除了肥胖症的流行，美国人自我报告的睡眠时间在过去的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，睡眠质量差和OSA是T2 DM的推定新风险因素。许多研究已经建立了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的强相关性，而与肥胖无关。然而，迄今为止，没有一项针对糖尿病前期或T2 DM的生活方式和/或药物干预的临床试验考虑到睡眠障碍的作用，尽管睡眠障碍在糖尿病前期和T2 DM中的患病率非常高，并且对胰岛素释放和作用有内在的不良影响。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前驱糖尿病或T2 DM的药物治疗更具抵抗力。母研究RISE研究旨在检测强化短期药物干预对保护或增强β细胞功能以预防或延迟明显T2 DM发展的影响。拟定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是ss细胞功能（胰岛素分泌）和胰岛素敏感性基线测量的预测因子，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-cell功能和胰岛素敏感性的独特详细量化。在随机化之前，受试者将接受一周的家庭腕动记录和一晚的实验室多导睡眠图（PSG）。我们假设在患有前驱糖尿病或早期T2 DM的受试者中，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β细胞功能降低和胰岛素敏感性降低相关。我们还假设，这些睡眠障碍中的每一种都会降低旨在保护和恢复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.