ESTABLISHING THE PRECURSORS OF THE METABOLIC SYNDROME IN CHILDREN

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。成人定义的代谢综合征(MSX)包括腹型肥胖、血脂异常、高血压、胰岛素抵抗以及导致心血管疾病风险增加的促炎和血栓前状态。肥胖在儿童中是一个日益严重的问题，并与2型糖尿病、高血压、管道异常和睡眠呼吸暂停有关。尽管这些特征看起来类似于成人中描述的MSX，但这个问题在儿科人群中还没有得到很好的研究。MSX的定义和发病机制可能会随着年龄的增长而改变。对儿童不断演变的发病机制的描述可能会导致制定特定年龄的定义，而针对特定年龄的病理可能会极大地影响临床护理。推测儿童MSX与早期出现外周和肝脏胰岛素抵抗有关，但胰岛素分泌正常，胰岛素抵抗进行性加重可导致继发于葡萄糖毒性的胰岛素分泌缺陷。进一步的假设是脂肪酸代谢异常，导致脂毒性损伤和进一步的胰岛素抵抗。研究人员建议进行横断面代谢研究，以确定特定年龄段(婴儿、幼儿、青春期前儿童和青少年)与MSX相关的代谢变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Metabolic Syndrome (MSX) as defined in adults consists of abdominal obesity, dyslipidemia, hypertenions, insulin resistance, and a proinflammatory and prothrombotic state resulting in increased risk of cardiovascular disease. Obesity is an ever-increasing problem in children and is associated with development of type 2 diabetes, hypertension, pipid abnormalities and sleep apnea. Although these features appear similar to the MSX described in adults, the problem has not been well studied in the pediatric population. It is likely that the definition and pathogenesis of MSX may change with age. Description of the evolving pathogenesis in children could lead to development of age-specific definitions, and targeting age-specific pathology could greatly impact clinical care. It is hypothesized that the MSX in children is associated with early presentation of perpheral and hepatic insulin resistance, but normal insulin secretion, and that progressive worsening of insulin resistance leads to defects of insulin secretion secondary to glucose toxicity. It is further hypothesized that fatty acid metabolism is abnormal leading to lipotoxic damage and further insulin resistance. Investigators propose cross-sectional metabolic studies to characterize the metabolic changes associated with MSX in defined age groups (infants, toddlers, prepubertal children and adolescents).