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经常睡得不到每晚建议的7个小时。令人震惊的是，维持的成年人 惯常的短睡眠时间（HSSD），例如医疗和军事人员，应急人员，轮班工人以及 学生，与保持足够睡眠的成年人相比，患有2型糖尿病（T2D）的可能性高约30％ 持续时间。此外，数据表明，实验强加的睡眠限制持续约3天到2周可能会损害 胰岛素对糖尿病前或衰老的人通常观察到的水平的敏感性。但是，尚不清楚数据是否 从实验性睡眠限制的严格控制的实验室研究转化为现实世界中的人 HSSD。此外，来自流行病学和实验室控制的现有数据既不适合机制 或针对HSSD的干预措施的潜在健康益处。将T2D风险与HSSD联系起来的分子生物标志物 可以通过以下方式帮助克服这些知识差距：（1）确定T2D风险的机制 世界HSSD和（2）通知睡眠延长是否会逆转这种风险。我们的初步数据确定了神经酰胺 将T2D风险与短时间持续时间联系起来的重要候选生物标志物。神经酰胺是中央中间脂质 在鞘脂代谢中，由于它们诱导胰岛素耐药性而被删除，并且始终如一 与包括T2D在内的心脏代谢疾病的发生率有关。那就是我们的中心假设是神经酰胺是 将T2D风险与HSSD联系起来的生物标志物和睡眠延期有望降低血浆神经酰胺并改善 胰岛素灵敏度。为了检验我们的中心假设，我们将进行现实睡眠的随机对照试验 超重和肥胖的成年人的扩展。参与者将完成1周的基线监控，然后 随机分配睡眠延长（床上≥8小时的目标≥8小时）或HSSD维护8周 （干预片段）。在基线和干预片段之后，参与者将完成严格的一夜之间 实验室就诊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 - Euglycemic夹具）。 AIM 1将确定睡眠延长对等离子体神经酰胺的影响，AIM 2将确定 睡眠延伸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志物来推进该领域 将T2D的风险与HSSD联系起来，并告知睡眠延长是否会逆转这种风险。这些知识可以改善 我们量化，跟踪和降低个人随着时间的T2D风险的能力，这可能对 当前饮食和基于体育活动的干预措施不太成功的人。如果有效，睡眠会延长 因此，有助于改善生活质量，并减少T2D对社会的健康和经济燃烧。