Biomarkers of Habitual Short Sleep and Related Cardiometabolic Risk

习惯性短睡眠和相关心脏代谢风险的生物标志物

• 批准号: 10734674
• 负责人: Christopher Michael Depner
• 金额: $ 76.3万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734674
• 关键词: Acute; Adult; Aging; American; Area; Automobile Driving; Beds; Biological Assay; Biological Markers; Cardiometabolic Disease; Ceramides; Chronic; Clinic; Clinical; Controlled Study; Data; Development; Diabetes Mellitus; Diet; Economic Burden; Effectiveness; Epidemic; Epidemiology; Foundations; Future; Glucose Clamp; Goals; Health; Health Benefit; Health Personnel; Home; Hour; Hyperinsulinism; Impairment; Incidence; Individual; Insulin Resistance; Intervention; Knowledge; Laboratories; Laboratory Study; Link; Lipids; Maintenance; Metabolism; Military Personnel; Modernization; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Overweight; Participant; Pathway Analysis; Pathway interactions; Persons; Physical activity; Plasma; Prediabetes syndrome; Prevention; Public Health; Quality of life; ROC Curve; Randomized; Randomized, Controlled Trials; Recommendation; Reporting; Risk; Risk Factors; Risk Reduction; Safety; Sleep; Sleep Deprivation; Societies; Sphingolipids; Students; Sum; Testing; Thinness; Time; Translating; United States; Visit; Work; adequate sleep; adult obesity; biomarker identification; biomarker signature; candidate marker; candidate validation; cardiometabolic risk; clinical risk; design; diabetes risk; emergency service responder; epidemiologic data; epidemiology study; experimental study; impaired glucose tolerance; improved; insulin sensitivity; metabolomics; molecular marker; novel; primary outcome; risk prediction

PROJECT SUMMARY/ABSTRACT Over one in three Americans regularly sleep less than the recommended 7 hours per night. Alarmingly, adults who maintain habitual short sleep durations (HSSD), such as medical and military personnel, emergency responders, shift workers, and students, are alarmingly ~30% more likely to develop type 2 diabetes (T2D) versus adults who maintain adequate sleep durations. Furthermore, data show that experimentally imposed sleep restriction lasting ~3 days to 2 weeks can impair insulin sensitivity to levels commonly observed in people with pre-diabetes or in aging. However, it is not known if data from rigidly controlled laboratory studies of experimental sleep restriction translates to people with real-world naturalistic HSSD. Furthermore, neither the existing data from epidemiological nor laboratory-controlled studies inform mechanisms or potential health benefits of interventions targeting HSSD. Molecular biomarkers that link risk of T2D with HSSD could help overcome these knowledge gaps by: (1) identifying mechanisms underlying risk of T2D linked to real- world HSSD and (2) informing whether sleep extension reverses such risk. Our preliminary data identified ceramides as important candidate biomarkers that link risk of T2D with short sleep duration. Ceramides are central intermediate lipids in sphingolipid metabolism and are particularly deleterious as they induce insulin resistance and are consistently associated with incidence of cardiometabolic disease including T2D. Thus, our central hypothesis is that ceramides are biomarkers that link risk of T2D with HSSD, and sleep extension is expected to lower plasma ceramides and improve insulin sensitivity. To test our central hypothesis, we will conduct a randomized controlled trial with real-world sleep extension in overweight and obese adults with HSSD. Participants will complete 1 week of baseline monitoring and then be randomized to either sleep extension (target ≥8 hours of nightly time in bed) or HSSD maintenance for 8 weeks at home (intervention segment). Following the baseline and intervention segments participants will complete rigorous overnight laboratory visits to assess plasma ceramides (targeted metabolomics assay) and insulin sensitivity (hyperinsulinemic- euglycemic clamp). Aim 1 will determine the impact of sleep extension on plasma ceramides and Aim 2 will determine the impact of sleep extension on insulin sensitivity. Our expected findings will advance the field by identifying biomarkers that link risk of T2D with HSSD and informing whether sleep extension reverses such risk. This knowledge could improve our ability to quantify, track, and reduce an individual’s risk of T2D over time, which could be especially impactful for people who are less successful with current diet and physical activity-based interventions. If effective, sleep extension would therefore help improve quality of life and reduce the health and economic burdens of T2D on society.

项目摘要/摘要 超过三分之一的美国人睡眠时间经常少于推荐的每晚7小时。令人担忧的是，成年人坚持 习惯性短睡眠持续时间(HSSD)，如医疗和军事人员、紧急响应人员、轮班工作人员和 与睡眠充足的成年人相比，学生患2型糖尿病(T2D)的可能性高出约30%，这一点令人震惊 持续时间。此外，数据显示，实验中施加的持续3天至2周的睡眠限制可能会损害 对糖尿病前期或老年人群中常见水平的胰岛素敏感性。然而，目前还不知道数据是否 来自严格控制的实验室研究的实验性睡眠限制转化为现实世界中的自然主义者 HSSD。此外，来自流行病学或实验室对照研究的现有数据都不能为机制提供信息。 或针对HSSD的干预措施的潜在健康益处。T2D与HSSD风险相关的分子生物标志物 可通过以下方式帮助克服这些知识差距：(1)确定与真实的 世界HSSD和(2)通知延长睡眠是否逆转了这种风险。我们的初步数据确定了神经酰胺 作为将T2D风险与短睡眠时间联系起来的重要候选生物标志物。神经酰胺是中枢中间脂类 在鞘脂新陈代谢中，尤其有害，因为它们诱导胰岛素抵抗，并一贯 与包括T2D在内的心脏代谢性疾病的发生率有关。因此，我们的中心假设是神经酰胺是 将T2D风险与HSSD和睡眠时间延长联系起来的生物标记物有望降低血浆神经酰胺并改善 胰岛素敏感性。为了检验我们的中心假设，我们将进行一项随机对照试验，试验对象为真实世界的睡眠 在超重和肥胖的患有HSSD的成年人中推广。参与者将完成为期一周的基线监测，然后 随机选择延长睡眠时间(目标是每晚8小时在床上)或在家中维持8周的≥ (干预部分)。在基线和干预部分之后，参与者将在一夜之间完成严格的 访问实验室以评估血浆神经酰胺(靶向代谢组学分析)和胰岛素敏感性(高胰岛素血症 正血糖钳夹)。目标1将确定睡眠时间延长对血浆神经酰胺的影响，目标2将确定 睡眠时间延长对胰岛素敏感性的影响。我们的预期发现将通过识别生物标记物来推动这一领域的发展 这将T2D的风险与HSSD联系起来，并告知延长睡眠时间是否逆转了这种风险。这一知识可以提高 我们能够量化、跟踪和降低个人随着时间的推移患T2D的风险，这可能对 目前以饮食和体力活动为基础的干预措施不太成功的人。如果有效，延长睡眠时间将 因此，有助于提高生活质量，减轻T2D对社会的健康和经济负担。