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: 8245078
• 负责人: Eve Van Cauter
• 金额: $ 26.41万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8245078
• 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.

我们的研究小组已经确定睡眠时间减少和睡眠质量下降是2型糖尿病的新风险因素 糖尿病2型糖尿病是由于胰腺β细胞不能释放足够的胰岛素， 补偿外周组织的胰岛素抵抗程度。睡眠时间缩短或 睡眠质量都导致胰岛素抵抗增加，而没有β细胞的适当补偿 release.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 与基线水平的慢波活动（SWA; EEG频谱功率在0.5-4 Hz 范围），睡眠-觉醒稳态的主要标志物。上一个赠款期内完成的研究 然而，已经表明，在重复的部分睡眠剥夺期间，SWA并没有增加，尽管 增加累积的清醒时间。SWA的这种“非稳态”与反复出现的睡眠丧失， 加速与年龄相关的睡眠稳态控制下降。SWA随着年龄的增长而显著下降， 性别差异已得到充分承认。我们最近发现SWA中存在明显的种族差异， 非裔美国人的SWA水平低于白人。SWA是一个非常稳定的特质依赖型 个体之间差异很大的特征。SWA的遗传性尚未得到证实。 评估。 这个项目的总体目标是检验一个假设，即由于年龄的原因， 种族，性别或遗传因素，更容易患上2型糖尿病，因为他们减少了 β细胞功能，因此更容易受到睡眠障碍的代谢挑战。到 为了实现这一目标，我们将对从研究中积累的非常大的数据库进行联合收割机统计分析 在过去的10年里，我们的小组进行了直接的实验方法和探索， 可能是SWA调节和糖尿病遗传易感性的基础的遗传因素。的 该项目的研究结果有望证明保持或改善睡眠的重要性 2型糖尿病的危害有哪些？ 相关性（参见说明）： 2型糖尿病的发病率在美国和全世界都在增加。这个项目将决定 减少睡眠时间和睡眠质量会降低患2型糖尿病的风险。这些发现可能会导致新的 2型糖尿病的治疗方法有哪些？