Adverse metabolic impact of sleep loss in older adults: insulin resistance

老年人睡眠不足对代谢的不利影响：胰岛素抵抗

• 批准号: 8707296
• 负责人: ORFEU M BUXTON
• 金额: $ 44.44万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8707296
• 关键词: Acute; Address; Adipose tissue; Adrenal Cortex Hormones; Adult; Age; Age-Years; Aging; American; Biopsy; Body fat; Chronic; Chronic Disease; Circadian Dysregulation; Circadian Rhythms; Data; Diabetes Mellitus; Elderly; Equilibrium; Exhibits; Fatty acid glycerol esters; Financial compensation; Functional disorder; Glucocorticoids; Glucose; Gold; Health; Healthy People 2020; Home environment; Hormonal; Hormonal Change; Hour; Human; Hydrocortisone; Incidence; Instruction; Insulin; Insulin Resistance; Insulin Signaling Pathway; Laboratory Study; Lead; Link; Measures; Metabolic; Metabolic Diseases; Metabolism; Modeling; Molecular; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathology; Periodicity; Peripheral; Phosphorylation; Photoperiod; Physiological; Prevalence; Protocols documentation; Quality of life; Recovery; Recurrence; Research; Research Priority; Risk; Role; Seminal; Severities; Sleep; Symptoms; Techniques; Testing; Time; Tissues; Visceral; Work; age related; diabetes risk; glucose metabolism; impaired glucose tolerance; improved; insulin sensitivity; intravenous glucose tolerance test; middle age; mortality; normal aging; obesity risk; research study; response; subcutaneous; therapy development; young adult

Insufficient sleep has been linked to adverse metabolic changes and increased risk of chronic disease including obesity, type 2 diabetes mellitus and early mortality. With age, most Americans increase visceral adiposity and become more likely to develop diabetes. Chronic insufficient sleep associated with 'normal aging' may be one of the factors involved in contributing to "metabolic aging'. Physiological changes in metabolism due to sleep loss for 1-2 weeks in young and middle-aged adults include reduced insulin sensitivity and hormonal changes that would increase the likelihood of obesity and diabetes in the long term. Our current data demonstrate that metabolic dysfunction occurs in young and older adults exposed to the combination of chronic sleep loss and recurrent circadian disruption for 3 weeks. Yet sleep loss experiments lengthen photoperiod, introducing a potential confounding effect on circadian rhythmicity, and circadian disruption itself has been shown to lead to adverse metabolic changes. Thus, the effects of sleep loss (with minimal circadian disruption) on glucose metabolism in older adults are not known. In Project 2, we will examine the metabolic responses to 3 weeks of sleep loss in a protocol with minimal circadian disruption to test the hypothesis that older adults will exhibit progressive decrements in total body and adipose tissue insulin sensitivity. We will determine the extent of the changes (glycemic responses to standardized meals, insulin sensitivity via euglycemic hyperinsulinemic clamps), the mechanisms of changes (via adipose tissue biopsy, sympathetic activation, and glucocorticoid activation) and the dynamics of changes (distinguishing effects over a few days and chronic effects over 3 weeks). Moreover, we hypothesize older adults will exhibit recovery of metabolic function with 1 week of sleep recovery. This Project will contribute to understanding the mechanisms by which sleep loss impairs metabolism in older adults, contributing to future research to reduce the risk of diabetes, improve existing therapies, and enhance the health and quality of life of older Americans whose sleep is insufficient.

睡眠不足与不利的新陈代谢变化和增加患慢性疾病的风险有关，包括肥胖、2型糖尿病和早期死亡。随着年龄的增长，大多数美国人的内脏肥胖症会增加，更有可能患上糖尿病。与“正常衰老”相关的慢性睡眠不足可能是导致“代谢衰老”的因素之一。年轻人和中年人由于睡眠不足1-2周而引起的新陈代谢的生理变化包括胰岛素敏感性降低和荷尔蒙变化，从长远来看，这会增加肥胖和糖尿病的可能性。我们目前的数据表明，长期睡眠不足和反复昼夜节律紊乱3周的年轻人和老年人都会发生代谢功能障碍。然而，睡眠缺失实验延长了光周期，对昼夜节律引入了潜在的混杂效应，而昼夜节律紊乱本身已被证明会导致不利的代谢变化。因此，睡眠不足(有最小的昼夜节律干扰)对老年人葡萄糖代谢的影响尚不清楚。在项目2中，我们将在最小的昼夜节律干扰的情况下检查3周睡眠不足时的代谢反应，以检验老年人全身和脂肪组织胰岛素敏感性进行性下降的假设。我们将确定变化的程度(对标准化膳食的血糖反应，通过正常血糖高胰岛素钳夹产生的胰岛素敏感性)，变化的机制(通过脂肪组织活检、交感神经激活和糖皮质激素激活)以及变化的动态(在几天内区分影响，在3周内产生慢性影响)。此外，我们假设老年人将在一周的睡眠恢复后表现出代谢功能的恢复。该项目将有助于了解睡眠不足损害老年人新陈代谢的机制，有助于未来降低糖尿病风险的研究，改进现有的治疗方法，并提高睡眠不足的老年美国人的健康和生活质量。