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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要超过三分之一的美国人每晚睡眠时间经常少于建议的 7 小时，而成年人的睡眠时间却经常少于建议的 7 小时。习惯性短睡眠时间 (HSSD)，例如医疗和军事人员、紧急救援人员、轮班工人和令人震惊的是，与保持充足睡眠的成年人相比，学生患 2 型糖尿病 (T2D) 的可能性要高出约 30% 此外，数据显示，持续约 3 天至 2 周的实验性睡眠限制可能会损害睡眠。糖尿病前期或衰老人群中常见的胰岛素敏感性水平尚不清楚。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自然主义的人此外，流行病学研究和实验室对照研究的现有数据都无法提供机制信息。或针对 HSSD 的干预措施的潜在健康益处，这些分子生物标志物将 T2D 风险与 HSSD 联系起来。可以通过以下方式帮助克服这些知识差距：(1) 识别与实际情况相关的 T2D 潜在风险机制世界 HSSD 和 (2) 告知延长睡眠时间是否可以逆转此类风险。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，神经酰胺是核心中间脂质。在鞘脂代谢中特别有害，因为它们会诱导胰岛素抵抗并且始终如一与包括 T2D 在内的心脏代谢疾病的发生率相关，因此，我们的中心假设是神经酰胺与将 T2D 风险与 HSSD 联系起来的生物标志物，延长睡眠预计会降低血浆神经酰胺并改善为了检验我们的中心假设，我们将对现实世界的睡眠进行随机对照试验。患有 HSSD 的超重和肥胖成人的扩展参与者将完成 1 周的基线监测，然后。随机选择延长睡眠（目标每晚床上时间≥8 小时）或在家维持 8 周的 HSSD （干预部分）。基线和干预部分将在一夜之间完成。实验室访问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）目标 1 将确定睡眠延长对血浆神经酰胺的影响，目标 2 将确定我们预期的研究结果将通过识别生物标志物来推进该领域的发展。将 T2D 风险与 HSSD 联系起来，并告知延长睡眠时间是否可以逆转此类风险。随着时间的推移，我们有能力量化、跟踪和降低个人患 T2D 的风险，这对于对于目前基于饮食和身体活动的干预措施效果不佳的人来说，如果有效的话，延长睡眠时间会有所帮助。因此有助于提高生活质量并减轻 T2D 对社会的健康和经济负担。