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以及肥胖、2 型糖尿病和早期死亡等慢性疾病风险增加有关。随着年龄的增长，大多数美国人内脏脂肪增多，患糖尿病的可能性也更大。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。中青年人1-2周睡眠不足会导致新陈代谢的生理变化，包括胰岛素敏感性降低和激素水平降低。我们目前的数据表明，长期睡眠不足和周期性昼夜节律紊乱相结合的年轻人和老年人会出现代谢功能障碍，但睡眠不足的实验时间却延长了。光周期，对昼夜节律产生潜在的混杂影响，而昼夜节律破坏本身已被证明会导致不利的代谢变化，因此，睡眠不足（昼夜节律破坏最小）对老年人葡萄糖代谢的影响尚不清楚。 2、我们将在昼夜节律干扰最小的方案中检查对 3 周睡眠不足的代谢反应，以检验老年人全身和脂肪组织胰岛素敏感性将表现出逐渐下降的假设。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）以及变化的动态（区分不同时期的影响）。几天和超过 3 周的慢性影响）。此外，我们假设老年人通过 1 周的睡眠恢复将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，有助于未来的研究，以降低患糖尿病的风险，改进现有疗法，并提高睡眠不足的美国老年人的健康和生活质量。