Markers of Autonomic and Metabolic Control in Childhood Obesity

儿童肥胖的自主和代谢控制标志物

• 批准号: 7337054
• 负责人: MICHAEL C K KHOO
• 金额: $ 36万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7337054
• 关键词: Adult; Affect; Age-Years; American; Biomedical Engineering; Blood; Blood Pressure; Blood specimen; Body Composition; Calibration; Cardiopulmonary Physiology; Cardiovascular Diseases; Cardiovascular Physiology; Child; Childhood; Chronic; Clinical; Communities; Computer Simulation; Data; Development; Devices; Diet; Disease; Disruption; Dyslipidemias; Early Diagnosis; Epidemic; Equilibrium; Excessive Daytime Sleepiness; Exposure to; Face; Fasting; Glucose; Heart Rate; Hispanics; Hypertension; Insulin; Insulin Resistance; Intervention Studies; Invasive; Knowledge; Lead; Life; Measurement; Measures; Metabolic; Metabolic Control; Metabolic syndrome; Methods; Modeling; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Overweight; Physical activity; Physiologic pulse; Prevalence; Pulse Pressure; Pulse taking; Rate; Regression Analysis; Research; Respiration; Risk Factors; Sampling; Screening procedure; Sleep Apnea Syndromes; Sleep Deprivation; Sleep Disorders; Stress; Surrogate Markers; Symptoms; Testing; Time; Triglycerides; Wakefulness; aged; base; cost; indexing; insulin sensitivity; interdisciplinary approach; intravenous glucose tolerance test; male; novel; novel strategies; sleep abnormalities; tool development; ward

DESCRIPTION (provided by applicant): Diet, physical activity, glucose-insulin control and autonomic activity are tied together in a delicate balance that, if disrupted, can lead to obesity and obesity-related disorders. Sleep disordered breathing (SDB), which is highly prevalent in obesity, can also contribute independently to autonomic imbalance and insulin resistance. Recent studies also suggest that the vicious cycle of interplay among these factors in childhood predisposes to the emergence of "metabolic syndrome", a clustering of obesity, hypertension, insulin resistance and dyslipidemia. Based on extensive preliminary data, we hypothesize that the strong association between autonomic and metabolic function enables the use of autonomic markers as noninvasive surrogate measures of insulin sensitivity in obese children that could be applied in clinical and community settings. To test this hypothesis, we will: (1) develop a method for noninvasive assessment of autonomic function, based on a computational model of pulse transit time variability and heart rate variability; (2) determine the quantitative relationships between the parameters of the autonomic control model and insulin sensitivity in childhood obesity; and (3) determine how SDB alters these relationships. The study employs a multidisciplinary approach with expertise in computational bioengineering, cardiopulmonary physiology, pediatric sleep disorders and pediatric obesity research. We will initiate this study in a homogenous sample of obese male Hispanic children aged 13-17 years, with and without SDB. Autonomic measurements (respiration, heart rate, blood pressure and pulse transit time) will be monitored during supine wakefulness and following exposure to autonomic challenges (cold face test and orthostatic stress). From these measurements, the parameters of a computational model of heart rate and pulse transit variability will be estimated and used to quantify baseline autonomic function and cardiovascular autonomic reactivity. Metabolic measurements will include body composition, fasting levels of insulin, glucose and triglyceride, and a frequently sampled intravenous glucose tolerance test. Regression analysis will be used to determine the correlations between the parameters representing autonomic and metabolic function, as well as how these correlations are affected by SDB. The knowledge derived from this study may lead to the development of a low-cost, portable device that can be used for early detection/monitoring of autonomic and metabolic abnormalities and sleep disruption in large populations of obese children.

描述（由申请人提供）：饮食、体力活动、葡萄糖-胰岛素控制和自主活动以微妙的平衡联系在一起，如果被破坏，可能导致肥胖和肥胖相关疾病。睡眠呼吸障碍（SDB）在肥胖症中非常普遍，也可以独立地导致自主神经失衡和胰岛素抵抗。最近的研究还表明，儿童时期这些因素之间相互作用的恶性循环容易导致出现“代谢综合征”，即肥胖、高血压、胰岛素抵抗和血脂异常的集合。基于广泛的初步数据，我们假设自主神经和代谢功能之间的强相关性，使自主神经标记物作为非侵入性替代措施的胰岛素敏感性肥胖儿童，可应用于临床和社区设置。为了验证这一假设，我们将：（1）基于脉搏传导时间变异性和心率变异性的计算模型，开发一种无创评估自主神经功能的方法;（2）确定自主神经控制模型参数与儿童肥胖症胰岛素敏感性之间的定量关系;（3）确定SDB如何改变这些关系。该研究采用了多学科方法，具有计算生物工程，心肺生理学，儿科睡眠障碍和儿科肥胖研究的专业知识。我们将在年龄在13-17岁的肥胖男性西班牙裔儿童（有和没有SDB）的同质样本中开始这项研究。在仰卧位清醒期间和暴露于自主神经激发（冷面试验和直立应激）后，将监测自主神经测量（呼吸、心率、血压和脉搏传导时间）。根据这些测量结果，将估计心率和脉搏传导变异性的计算模型的参数，并用于量化基线自主神经功能和心血管自主神经反应性。代谢测量将包括身体成分，胰岛素，葡萄糖和甘油三酯的空腹水平，以及频繁采样的静脉葡萄糖耐量试验。回归分析将用于确定代表自主神经和代谢功能的参数之间的相关性，以及这些相关性如何受到SDB的影响。从这项研究中获得的知识可能会导致开发出一种低成本、便携式设备，可用于早期检测/监测大量肥胖儿童的自主神经和代谢异常以及睡眠中断。