ESTABLISHING THE PRECURSORS OF THE METABOLIC SYNDROME IN CHILDREN

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。成人代谢综合征（MSX）包括腹部肥胖、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形成前状态。肥胖在儿童中是一个日益严重的问题，与2型糖尿病、高血压、血脂异常和睡眠呼吸暂停的发展有关。尽管这些特征与成人的MSX相似，但在儿科人群中尚未得到很好的研究。MSX的定义和发病机制可能随着年龄的增长而改变。对儿童发病机制的描述可能会导致年龄特异性定义的发展，针对年龄特异性病理可能会极大地影响临床护理。假设儿童的MSX与早期外周和肝脏胰岛素抵抗有关，但胰岛素分泌正常，胰岛素抵抗的进行性恶化导致继发于葡萄糖毒性的胰岛素分泌缺陷。进一步假设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，以确定在特定年龄组（婴儿、幼儿、青春期前儿童和青少年）中与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).