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: 7677984
• 负责人: MICHAEL C K KHOO
• 金额: $ 34.72万
• 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 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677984
• 关键词: 19 year old; Adult; Affect; American; Biomedical Engineering; Blood; Blood Pressure; Blood specimen; Body Composition; Calibration; Cardiopulmonary Physiology; Cardiovascular Diseases; Cardiovascular Physiology; Child; Childhood; Chronic; Clinical; Computer Simulation; Data; Development; Devices; Diet; Disease; Dyslipidemias; Early Diagnosis; Epidemic; Equilibrium; Excessive Daytime Sleepiness; Exposure to; Face; Fasting; Glucose; Heart Rate; Hispanics; Hypertension; Insulin; Insulin Resistance; Intervention Studies; 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; 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; community setting; cost; heart rate variability; high risk; indexing; insulin sensitivity; interdisciplinary approach; intravenous glucose tolerance test; male; novel; novel strategies; obesity in children; 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，体育锻炼，葡萄糖 - 胰岛素控制和自主神经活动以微妙的平衡并列在一起，如果破坏，可能会导致肥胖和与肥胖有关的疾病。睡眠失调的呼吸（SDB）在肥胖症中高度普遍，也可以独立地促进自主神经失衡和胰岛素抵抗。最近的研究还表明，这些因素之间的相互作用的恶性循环倾向于“代谢综合征”的出现，肥胖，高血压，胰岛素抵抗和血脂异常的聚类。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密切关联使自主标记物用作肥胖儿童中胰岛素敏感性的无创替代措施，可以应用于临床和社区环境。为了检验这一假设，我们将基于脉冲传输时间变异性和心率变异性的计算模型，为自主功能的无创评估进行非侵入性评估的方法； （2）确定儿童肥胖症中自主神经控制模型参数与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。该研究采用多学科方法，具有计算生物工程，心肺生理学，小儿睡眠障碍和儿科肥胖研究方面的专业知识。我们将在肥胖的男性西班牙裔儿童的同质样本中发起这项研究，其中有和没有SDB。在仰卧觉醒并暴露于自主挑战（冷面检验和体位应力）之后，将监测自主测量（呼吸，心率，血压和脉搏转运时间）。从这些测量值中，将估算心率和脉搏传输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性反应性。代谢测量值将包括身体成分，胰岛素的禁食水平，葡萄糖和甘油三酸酯以及经常采样的静脉葡萄糖耐受性测试。回归分析将用于确定代表自主和代谢功能的参数之间的相关性，以及这些相关性如何受SDB的影响。从这项研究中得出的知识可能导致开发低成本的便携式设备，该设备可用于早期检测/监测自主和代谢异常，并在大量肥胖儿童中造成睡眠破坏。