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.

睡眠不足与不良代谢变化和慢性疾病风险增加有关，包括肥胖，2型糖尿病和早期死亡。随着年龄的增长，大多数美国人增加内脏肥胖，更容易患糖尿病。与“正常衰老”相关的慢性睡眠不足可能是导致“代谢性衰老”的因素之一。由于年轻人和中年人睡眠不足1-2周导致的新陈代谢生理变化包括胰岛素敏感性降低和激素变化，这将增加长期肥胖和糖尿病的可能性。我们目前的数据表明，代谢功能障碍发生在年轻人和老年人暴露于慢性睡眠不足和经常性昼夜节律紊乱的组合3周。然而，睡眠不足的实验延长了光周期，对昼夜节律产生了潜在的混淆效应，而昼夜节律的破坏本身也被证明会导致不利的代谢变化。因此，睡眠不足（昼夜节律紊乱最小）对老年人葡萄糖代谢的影响尚不清楚。在项目2中，我们将在最小昼夜节律破坏的方案中检查对3周睡眠丧失的代谢反应，以检验老年人将表现出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）和变化的动力学（区分几天内的影响和3周内的慢性影响）。此外，我们假设老年人将在1周的睡眠恢复中恢复代谢功能。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，有助于未来的研究，以降低糖尿病的风险，改善现有的治疗方法，并提高睡眠不足的美国老年人的健康和生活质量。