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

非裔美国人患2型糖尿病的风险明显高于非西班牙裔白人。尽管人们长期承认这种种族差异并试图消除它，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承受更大的健康负担。因此，迫切需要更多的努力来消除糖尿病的这种差异，以实现非裔美国人的健康平等。实验室和观察性研究发现(1)睡眠不足与糖尿病风险增加之间存在显著关联；(2)与白人相比，非裔美国人的睡眠时间更短，睡眠质量更差。然而，迄今为止还没有研究明确地检验睡眠不足是否在一定程度上导致了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生物行为调节因子。事实上，尽管人们普遍认为(1)睡眠时间短会改变昼夜节律阶段，(2)昼夜节律中断会产生代谢紊乱，(3)褪黑激素节律直接影响β细胞功能，但昼夜节律中断之前并未被认为是睡眠和糖尿病风险之间的关键中介。因此，本研究的三个主要目标是：(1)对人们家中的睡眠进行全面和生态有效的评估；(2)通过客观控制光照和样本采集时间来评估家庭环境中的昼夜节律阶段；(3)确定家庭睡眠和昼夜节律测量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。我们的糖尿病风险的主要标志将是胰岛素敏感性的松田指数，通过频繁取样的口服葡萄糖耐量试验来估计。次要结果包括曲线下面积血糖水平、性格指数、炎症标志物（C反应蛋白）、血压、心率变异性和脂质谱。我们计划研究72名非裔美国人和72名非西班牙裔白人，他们没有糖尿病或睡眠障碍。我们的初步数据表明：1)支持在睡眠持续时间、结构和时间上存在种族差异；(2)支持睡眠不足可能介导某些健康差异的假设；(3)支持在昼夜节律时间上存在种族差异；(4)证明在家中进行无人看管的多导睡眠监测的可行性。(5)证明家庭昼夜节律阶段评估数据的可行性和有效性；(6)证明在本研究中使用的完整缩短方案的可行性。这个重要的多学科项目将对非裔美国人糖尿病风险增加的生物行为机制产生独特的见解，并可能导致新的针对糖尿病的干预措施的发展，包括延长就寝时间或规律和时间治疗治疗。此申请是为了响应PA-09-262“NIDDK疾病中的健康差异”。

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".