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率。随着年龄的增长，大多数美国人会增加内脏肥胖，并变得更有可能患上糖尿病。长期与“正常衰老”相关的长期睡眠不足可能是导致“代谢衰老”的因素之一。年轻和中年成年人因睡眠损失1-2周而导致代谢的生理变化，包括胰岛素敏感性和荷尔蒙变化的降低，这将增加肥胖和糖尿病的可能性，而我们当前的成年人的可能性证明了这一点。暴露于慢性睡眠损失和昼夜节律损失实验的结合2，我们将在协议中检查对3周睡眠损失的代谢反应，并测试了老年人将在总体和脂肪组织胰岛素敏感性中表现出逐渐减少的假设。我们将确定变化的程度（对标准餐的血糖反应，通过eugememal高胰岛素夹的胰岛素敏感性），变化的机制（通过脂肪组织活检，交感神经激活和糖皮质激活激活）以及在几天和3周内效应的变化的动力学）。此外，我们假设老年人将在睡眠恢复1周的情况下表现出代谢功能的恢复。该项目将有助于理解睡眠损失损害老年人的新陈代谢的机制，从而有助于未来的研究，以减少糖尿病的风险，改善现有疗法，并增强睡眠不足的老年人的健康和生活质量。