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.

项目总结/摘要 超过三分之一的美国人经常每晚睡眠时间少于建议的7小时。令人担忧的是， 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，轮班工人， 与保持充足睡眠的成年人相比，学生患2型糖尿病（T2 D）的可能性高出约30 持续时间。此外，数据显示，实验性的睡眠限制持续约3天至2周， 胰岛素敏感性降低到糖尿病前期或老年人中常见的水平。然而，目前尚不清楚数据是否 从严格控制的实验室研究的实验性睡眠限制转化为人们与现实世界的自然主义 HSSD。此外，流行病学研究和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。将T2 D风险与HSSD联系起来的分子生物标志物 （1）查明与真实的- 世界HSSD和（2）告知睡眠延长是否逆转这种风险。我们的初步数据确定了神经酰胺 作为重要的候选生物标志物，将T2 D风险与睡眠时间短联系起来。神经酰胺是中心中间脂质 在鞘脂代谢中是特别有害的，因为它们诱导胰岛素抗性， 与心脏代谢疾病（包括T2 D）的发病率相关。因此，我们的中心假设是，神经酰胺是 将T2 D风险与HSSD联系起来的生物标志物和睡眠延长预计会降低血浆神经酰胺并改善 胰岛素敏感性为了验证我们的中心假设，我们将进行一项随机对照试验， 在超重和肥胖成人HSSD中的扩展。参与者将完成1周的基线监测，然后 随机分配至睡眠延长组（目标为每晚卧床时间≥8小时）或HSSD维持组，在家维持8周 （发言部分）。在基线和干预部分之后，参与者将在夜间完成严格的 实验室访视，以评估血浆神经酰胺（靶向代谢组学测定）和胰岛素敏感性（高胰岛素血症， 正葡萄糖钳夹）。目标1将确定睡眠延长对血浆神经酰胺的影响，目标2将确定 睡眠延长对胰岛素敏感性的影响。我们预期的发现将通过识别生物标志物来推进该领域 将T2 D风险与HSSD联系起来，并告知睡眠延长是否会逆转这种风险。这些知识可以提高 我们量化、跟踪和降低个人T2 D风险的能力，这可能对以下方面特别有影响： 那些在目前的饮食和基于身体活动的干预措施中不太成功的人。如果有效，睡眠延长将 因此，有助于提高生活质量，减少T2 D对社会的健康和经济负担。