Home sleep and circadian phase: mediators of racial disparities in diabetes risk

描述(由申请人提供)：摘要：非裔美国人比非西班牙裔白人患2型糖尿病的风险要大得多。尽管长期以来人们认识到这一种族差距并试图消除它，但它仍然存在。糖尿病与生活质量下降、预期寿命缩短和经济负担增加有关，因此非裔美国人比非西班牙裔白人面临更大的健康负担。因此，为了实现非裔美国人的健康公平，迫切需要做出更多努力来消除糖尿病方面的这种差距。实验室和观察性研究已经观察到(1)睡眠不足与糖尿病风险增加之间的显著关联，以及(2)与白人相比，非裔美国人的睡眠持续时间更短，睡眠质量更差。然而，到目前为止，还没有研究明确检查睡眠不足是否在一定程度上导致非裔美国人患糖尿病的风险增加。因此，我们建议研究睡眠时间、睡眠质量和昼夜节律紊乱作为糖尿病风险种族差异的新的生物行为介体。事实上，尽管人们已经认识到(1)短睡眠时间改变了昼夜节律，(2)昼夜节律紊乱会产生代谢紊乱，(3)褪黑激素节律直接影响β细胞功能，但此前昼夜节律紊乱并未被认为是睡眠和糖尿病风险之间的关键中介因素。因此，这项研究的三个主要目标是：(1)对人们家庭中的睡眠进行全面和生态上有效的评估；(2)通过客观地控制光照和样本采集的时间来评估家庭环境中的昼夜节律阶段；以及(3)确定家庭睡眠和昼夜节律措施的差异是否部分解释了非裔美国人和非西班牙裔白人之间糖尿病风险因素的差异。我们糖尿病风险的主要标志将是松田胰岛素敏感性指数，该指数是通过频繁采样的口服葡萄糖耐量试验估计的。次要结果将包括血糖水平曲线下面积、倾向指数、炎症标志物(C-反应蛋白)、血压、心率变异性和血脂谱。我们计划研究72名非裔美国人和72名没有糖尿病或睡眠障碍的非西班牙裔白人。我们的初步数据表明：1)支持睡眠持续时间、结构和时间的种族差异；(2)支持睡眠不足可能调节某些健康差异的假设；(3)支持昼夜节律存在种族差异；(4)论证了无人看管的居家PSG的可行性；(5)论证了来自家庭昼夜节律阶段评估的数据的可行性和有效性；(6)论证了本研究中使用的完整的简化方案的可行性。这一重要的多学科项目将对非裔美国人糖尿病风险增加背后的生物行为机制产生独特的见解，并可能导致开发新的有针对性的糖尿病干预措施，包括延长就寝时间或规律以及时序治疗。这项申请是对PA-09-262“NIDDK疾病中的健康差异”的回应。

DESCRIPTION (provided by applicant): Summary African Americans are at significantly greater risk of developing type 2 diabetes than non-Hispanic whites. Despite the long-standing recognition of this racial disparity and attempts to eliminate it, it persists. Diabetes is associaed with reduced quality of life, decreased life expectancy and increased economic burden, and therefore African Americans experience a greater health burden than non-Hispanic whites. Thus, more efforts to combat this disparity in diabetes is urgently needed in order to achieve health equity for African Americans. Laboratory and observational studies have observed (1) significant associations between deficient sleep and increased diabetes risk and (2) shorter sleep durations and poorer sleep quality in African Americans compared to whites. No research to date, however, has explicitly examined whether deficient sleep partially accounts for the increased diabetes risk in African Americans. Therefore, we propose to examine sleep duration, sleep quality and circadian disruption as novel biobehavioral mediators of the racial disparity in diabetes risk. Indeed, despite it being well-recognized that (1) short sleep durations alter circadian phase, (2) circadian disruption produces metabolic disturbances, and (3) the melatonin rhythm directly impacts beta-cell function, circadian disruption has not previously been considered as a key mediator between sleep and diabetes risk. Thus the 3 primary goals of this study are to (1) conduct comprehensive and ecologically-valid assessments of sleep in people's homes, (2) assess circadian phase in the home environment by objectively controlling for light exposure and timing of sample collection and (3) determine if differences in home sleep and circadian measures partially explain differences in diabetes risk factors between African Americans and non- Hispanic whites. Our primary marker of diabetes risk will be the Matsuda Index of insulin sensitivity, estimated from a frequently-sampled oral glucose tolerance test. Secondary outcomes will include area-under-the-curve of glucose levels, disposition index, and a marker of inflammation (C - reactive protein), blood pressure, heart-rate variability, and lipid profiles. We plan to study 72 African Americans and 72 non-Hispanic whites without diabetes or sleep disorders. We have preliminary data that 1) support the existence of racial differences in the duration, structure and timing of sleep, (2) support our hypothesis that deficient sleep may mediate some health disparities, (3) support the existence of racial differences in circadian timing, (4) demonstrate the feasibility of conducting unattended in-home PSG, (5) demonstrate the feasibility and validity of data from at- home circadian phase assessments and (6) demonstrate the feasibility of the complete shortened protocol to be used in this study. This important multidisciplinary project will yield unique insights into the bio behavioral mechanisms underlying increased diabetes risk in African-Americans and will likely lead to the development of novel targeted interventions for diabetes including bedtime extension or regularity and chrono-therapeutic treatments. This application is in response to PA-09-262 "Health Disparities in NIDDK Diseases".