Childhood Precursors for Adulthood Metabolic Syndrome

描述（由申请人提供）：本拨款申请是一项纵向队列研究，是为了响应 NIH 申请请求 RFA-HD-03-033“确定儿童代谢综合征的前体”而提交的。我们的总体目标是利用 Fels 纵向研究中收集的 350 名成年男性和 348 名成年女性出生时的长期系列数据，将成人代谢综合征[根据国家胆固醇教育计划 (NCEP) 成人治疗小组 III (ATP III) 的定义]与其儿童期危险因素联系起来。 ATP llI 将成人代谢综合征定义为具有超过标准值的三个、四个或五个危险因素，即男性腰围 >102 厘米，女性腰围 >88 厘米；血压>130/>85毫米汞柱；血浆甘油三酯水平>150 mg/dL；男性血浆高密度脂蛋白胆固醇水平<40毫克/分升，女性血浆高密度脂蛋白胆固醇水平<50毫克/分升；空腹血糖>110 mg/dL。我们建议（1）确定代谢综合征的任何组成部分的病理值是否始于儿童期；如果是的话，为这些生物标志物建立童年标准值； (2) 检查这 698 名 Fels 成年人中青春期期间收集的体脂、脂肪分布、去脂体重、血脂谱、胰岛素抵抗、血压、瘦素、脂联素和 C 反应蛋白 (CRP) 值的变化和性别二态性与成年后是否存在代谢综合征的关系； (3) 将成年期心脏结构和血流动力学参数的变化与身体脂肪、脂肪分布和去脂体重的同期变化以及三年内的代谢综合征联系起来。我们将使用 NCEP ATP III 标准 110 mg/dL 和美国糖尿病协会 (ADA) 新推荐的空腹血糖受损标准 100 mg/dL 进行拟议研究，以阐明较低阈值的诊断意义。 通过将儿童数据与成人病理联系起来来阐明不利关系，可能会导致能够检测出代谢综合征风险升高的儿童，并暗示2型糖尿病和心血管疾病的风险升高。菲尔斯的长期连续记录为我们以经济高效的方式实现目标提供了独特的机会。 Fels 纵向研究的参与者在出生时就被登记，并且不是根据与任何临床状况相关的因素来选择的。因此，所揭示的关系和从拟议研究中得出的推论应反映肥胖、高血压、血脂异常和糖耐量受损发展的自然史，因此应有助于及早识别有代谢综合征风险的儿童。

DESCRIPTION (provided by applicant): This grant application is a longitudinal cohort study submitted in response to the NIH Request for Applications, RFA-HD-03-033, "Establishing the Precursors of the Metabolic Syndrome in Children ". Our overall goal is to link the metabolic syndrome in adults [as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) to their childhood risk factors using long-term serial data collected from birth in 350 adult males and 348 adult females in the Fels Longitudinal Study. The ATP llI defines the metabolic syndrome in adults as having a cluster of three, four, or five risk factors that exceed criterion values, namely, waist circumference >102 cm for men and >88 cm for women; blood pressure >130/>85 mm Hg; plasma triglyceride level >150 mg/dL; plasma HDL-cholesterol level <40 mg/dL for men and <50mg/dL for women; and fasting plasma glucose >110 mg/dL. We propose (1) to determine if the onset of pathological values for any of the components of the metabolic syndrome begins in childhood; and, if so, to establish childhood criterion values for these biomarkers; (2) to examine in these 698 Fels adults changes and sexual dimorphism in values collected during their pubertal years for body fat, fat distribution, fat-free mass, lipid profiles, insulin resistance, blood pressure, leptin, adiponectin and C-reactive protein (CRP) in relation to the presence or absence of the metabolic syndrome in adulthood; and, (3) to relate adulthood changes in cardiac structure and hemodynamic parameters to contemporaneous changes in body fat, fat distribution, and fat-free mass and to metabolic syndrome over a three-year interval. We will conduct the proposed study using both the NCEP ATP III criterion of 110 mg/dL and the American Diabetes Association's (ADA) newly recommended criterion of 100 mg/dL for impaired fasting plasma glucose in order to elucidate the diagnostic implications of the lower threshold. Elucidating adverse relationships by linking childhood data to adult pathology may lead to the ability to detect children at elevated risk for the metabolic syndrome and, by implication, for type 2 diabetes mellitus and cardiovascular disease. The Fels long-term serial records provide a unique opportunity to accomplish our aims in an economical and efficient manner. Participants in the Fels Longitudinal Study are enrolled at birth and are not selected in regard to factors associated with any clinical condition. Consequently, the relationships revealed and the inferences drawn from the proposed study should reflect the natural history of the development of obesity, hypertension, dyslipidemia, and impaired glucose tolerance, and thus, should lead to the early identification of children at risk for the metabolic syndrome.