Childhood Precursors for Adulthood Metabolic Syndrome

描述（由申请人提供）：本资助申请是一项纵向队列研究，应NIH申请要求提交，RFA-HD-03-033，“建立儿童代谢综合征的前体”。我们的总体目标是使用Fels纵向研究中350名成年男性和348名成年女性从出生起收集的长期系列数据，将成人代谢综合征[由国家胆固醇教育计划（NCEP）成人治疗小组III（ATP III）定义]与其儿童期风险因素联系起来。ATP III将成年人的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的集群，即，男性腰围>102 cm，女性腰围>88 cm;血压>130/>85 mm Hg;血浆甘油三酯水平>150 mg/dL;男性血浆HDL-胆固醇水平<40 mg/dL，女性血浆HDL-胆固醇水平<50 mg/dL;空腹血糖>110 mg/dL。我们建议（1）确定代谢综合征的任何组分的病理学值的发作是否始于儿童期;如果是，则建立这些生物标志物的儿童标准值;（2）在这698名Fels成年人中检查青春期期间收集的体脂、脂肪分布、去脂质量、脂质谱、胰岛素抵抗的值的变化和性二态性，血压、瘦素、脂联素和C-反应蛋白（CRP）与成年期代谢综合征的存在或不存在的关系;和（3）将心脏结构和血液动力学参数的成年期变化与体脂、脂肪分布和无脂肪质量的同期变化以及与代谢综合征在三年时间间隔内相关联。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进行拟定研究，以阐明下限阈值的诊断意义。 通过将儿童数据与成人病理学联系起来来阐明不良关系，可能会导致检测代谢综合征风险升高的儿童的能力，并暗示2型糖尿病和心血管疾病。Fels的长期连续记录提供了一个独特的机会，以经济有效的方式实现我们的目标。Fels纵向研究的参与者在出生时就被招募，并且没有根据与任何临床状况相关的因素进行选择。因此，从拟议的研究中揭示的关系和得出的推论应反映肥胖，高血压，血脂异常和糖耐量受损的发展的自然史，因此，应导致早期识别儿童的代谢综合征的风险。

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.