ROLE OF SLOW-WAVE ACTIVITY IN DIABETES RISK

慢波活动在糖尿病风险中的作用

• 批准号: 8448187
• 负责人: Eve Van Cauter
• 金额: $ 25.04万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8448187
• 关键词: Adult; African American; Age; Aging; Beta Cell; Cell physiology; Characteristics; Chromosome Mapping; Chronic; Circadian Rhythms; Coin; DNA; Data; Data Set; Databases; Development; Diabetes Mellitus; Disease; Doctor of Philosophy; Elderly; Electroencephalography; Epidemiologic Studies; Ethnic Origin; Family; Family member; Financial compensation; Future; Genes; Genetic; Genetic Predisposition to Disease; Goals; Grant; Health; Heritability; Homeostasis; Human; Incidence; Individual; Individual Differences; Instruction; Insulin; Insulin Resistance; Intravenous; Laboratories; Laboratory Study; Lead; Life; Link; Measures; Medical; Metabolic; Modeling; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Peripheral; Phenotype; Play; Polysomnography; Population Heterogeneity; Predisposition; Prevalence; Preventive; Principal Investigator; Protocols documentation; Recovery; Recurrence; Registries; Regulation; Research Personnel; Risk; Risk Factors; Rodent; Role; Sample Size; Sampling; Serum; Severities; Sex Characteristics; Sleep; Sleep Deprivation; Sleep disturbances; Structure of beta Cell of islet; Testing; Time; Tissues; Wakefulness; Woman; Work; age difference; age related; allostasis; base; blood glucose regulation; cohort; deprivation; design; diabetes risk; ethnic difference; genetic linkage; genetic pedigree; glucose tolerance; improved; member; middle age; non-diabetic; novel; novel strategies; programs; sex; sleep regulation; socioeconomics; trait; young adult

Our group has identified reduced sleep duration and reduced sleep quality as novel risk factors for type 2 diabetes. Type 2 diabetes develops when the pancreatic beta cells fail to release enough insulin to compensate for the degree of insulin resistance of peripheral tissues. Reductions in sleep duration or in sleep quality both result in increased insulin resistance without appropriate compensation by beta cell release. We have further obtained evidence indicating that beta cell function in young healthy adults is strongly correlated with baseline levels of slow-wave activity (SWA; EEG spectral power in the 0.5-4 Hz range), the primary marker of sleep-wake homeostasis. Studies completed during the previous grant period have, however, shown that during repeated partial sleep deprivation, SWA does not increase despite the increased cumulated duration of wakefulness. This "allostasis" of SWA with recurrent sleep loss could accelerate age-related declines in the homeostatic control of sleep. SWA decreases markedly with age and sex differences have been well-recognized. We have recently identified robust ethnic differences in SWA, with African-Americans having lower levels of SWA than whites. SWA is a remarkably stable trait-dependent characteristic that varies greatly from one individual to another. Heritability of SWA has not yet been evaluated. The overall goal of this project is to test the hypothesis that individuals with low SWA, because of age, ethnicity, sex or genetic factors, are more susceptible to develop type 2 diabetes because they have reduced beta cell function and, therefore a higher vulnerability to the metabolic challenge of sleep disturbances. To achieve this goal, we will combine statistical analyses of the very large data base accumulated from studies conducted by our group during the past 10 years, with a direct experimental approach and an exploration of genetic factors that could underlie both the regulation of SWA and genetic susceptibility to diabetes. The findings from this project are expected to demonstrate the importance of preserving or improving sleep quality to reduce the risk of type 2 diabetes. RELEVANCE (See instructions): The incidence of type 2 diabetes is increasing in the U.S. and worldwide. This project will determine the role of reductions in sleep duration and quality in the risk of type 2 diabetes. The findings could lead to novel strategies to delay the development or reduce the severity of type 2 diabetes.

我们的小组已经确定睡眠时间缩短和睡眠质量降低是2型糖尿病的新的危险因素 糖尿病。当胰岛β细胞不能释放足够的胰岛素，从而导致2型糖尿病。 补偿外周组织的胰岛素抵抗程度。睡眠时间的缩短或 睡眠质量都会导致胰岛素抵抗的增加，而不是由β细胞进行适当的补偿 放手。我们进一步获得的证据表明，年轻健康成年人的β细胞功能是 与慢波活动的基线水平(SWA；0.5-4赫兹的脑电频谱功率)密切相关 范围)，睡眠-觉醒动态平衡的主要标志。在上一个资助期内完成的研究 然而，研究表明，在反复部分睡眠剥夺期间，SWA并没有增加，尽管 增加了累积的清醒时长。反复失眠的SWA的这种“同素作用”可能 加速与年龄相关的睡眠平衡控制能力的下降。SWA随年龄的增长而显著降低， 性别差异已经得到了广泛的认识。我们最近发现了西佤邦存在明显的种族差异， 与白人相比，非洲裔美国人的SWA水平更低。SWA是一个非常稳定的特征依赖型 个体差异很大的特征。SWA的遗传力尚未达到 已评估。 这个项目的总体目标是检验这样一种假设，即由于年龄原因，SWA低的个体 种族、性别或遗传因素，更容易患上2型糖尿病，因为他们 β细胞功能，因此对睡眠障碍的代谢挑战有更高的脆弱性。至 为了实现这一目标，我们将结合从研究中积累的大量数据库的统计分析 由我们团队在过去10年中进行的，以直接的实验方法和探索 基因因素既可能是调节SWA的基础，也可能是糖尿病的遗传易感性。这个 该项目的研究结果有望证明保持或改善睡眠的重要性。 高质量，以降低患2型糖尿病的风险。 相关性(请参阅说明)： 在美国和世界范围内，2型糖尿病的发病率正在上升。这个项目将决定 减少睡眠时间和质量，降低患2型糖尿病的风险。这些发现可能会带来新的 延缓2型糖尿病发展或减轻其严重程度的策略。