Markers of Autonomic and Metabolic Control in Childhood Obesity

描述（由申请人提供）：饮食，身体活动，葡萄糖-胰岛素控制和自主神经活动在一个微妙的平衡中联系在一起，如果被破坏，可能导致肥胖和肥胖相关的疾病。睡眠呼吸障碍（SDB）在肥胖中非常普遍，也可能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，这些因素在儿童时期相互作用的恶性循环容易导致“代谢综合征”的出现，即肥胖、高血压、胰岛素抵抗和血脂异常。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烈关联使得自主神经标记物可以作为肥胖儿童胰岛素敏感性的非侵入性替代测量，可以应用于临床和社区环境。为了验证这一假设，我们将：(1)开发一种基于脉冲传递时间变异性和心率变异性计算模型的自主神经功能无创评估方法；(2)确定自主控制模型参数与儿童肥胖胰岛素敏感性之间的定量关系；(3)确定深发展如何改变这些关系。该研究采用多学科方法，在计算生物工程、心肺生理学、儿童睡眠障碍和儿童肥胖研究方面具有专业知识。我们将在13-17岁的西班牙裔男性肥胖儿童（有或没有SDB）的同质样本中启动这项研究。自主测量（呼吸、心率、血压和脉搏传递时间）将在仰卧清醒期间和暴露于自主挑战（冷面测试和直立应激）后进行监测。根据这些测量，心率和脉搏传递变异性计算模型的参数将被估计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、空腹胰岛素、葡萄糖和甘油三酯水平，以及经常取样的静脉葡萄糖耐量测试。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到SDB的影响。从这项研究中获得的知识可能会导致一种低成本的便携式设备的开发，这种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。

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.