Development of a childhood metabolic syndrome risk score for predicting adult dis

描述（由申请人提供）： 儿童代谢综合征风险评分预测成人疾病的发展项目概要：代谢综合征描述了一组医学发现，这些发现似乎与增加糖尿病和心脏病风险的潜在过程有关。诊断儿童代谢综合征的最佳方法仍不清楚，尽管目前的尝试似乎导致种族/民族差异。我们建议通过使用已知的疾病风险标志物以及糖尿病和心脏病发展的长期信息，为儿童制定一个新的种族/民族特异性MetS风险评分。被确定为成人疾病风险增加的儿童可以成为加强预防工作的目标。 公共卫生相关性： 儿童代谢综合征风险评分预测成人疾病的发展叙述：代谢综合征（MetS）是一组心血管指标，这些指标似乎与一个鲜为人知的潜在过程有关，该过程会增加2型糖尿病（T2 DM）和冠状动脉疾病（CAD）的风险。代谢综合征的这些组成部分包括腹部肥胖、高脂血症、低HDL胆固醇、高血压和胰岛素抵抗。MetS的诊断目前是基于这些不同成分的截止点的组合。对于儿童，目前还没有一个共识，关于哪几套儿科代谢综合征的标准在临床上使用。这种不确定性在很大程度上与将长期结果与MetS诊断联系起来的困难有关，因为儿童需要更长的时间才能发展为T2 DM和CAD。此外，已证明成人MetS标准在预测T2 DM和CAD的能力方面存在种族/民族差异。我们建议使用其他已知与成人冠状动脉疾病长期风险相关的血清因素，为儿童设计一个种族/民族特异性MetS风险评分。这些“替代”风险因素包括空腹胰岛素、C反应蛋白、尿酸和丙氨酸氨基转移酶。然后，我们将使用包括儿童期MetS信息和成人结局数据在内的纵向数据，验证并确定该风险评分的风险阈值。我们的计划有三个方面。我们将首先使用国家健康和营养检查调查（NHANES）来测试当前的儿科MetS标准，并假设我们将证明当前MetS标准预测成人疾病替代品升高的能力存在种族/民族差异。然后，我们将使用NHANES来设计一个种族/民族特定的儿科代谢综合征风险评分，使用我们的替代品作为“目标”的海拔高度，并使用线性回归来制定这个风险评分使用测量代谢综合征的组成部分。最后，我们将使用脂质研究诊所/普林斯顿随访研究验证此风险评分并设置最佳预测长期结局的阈值，其中数据来自MetS的儿童测量和成人疾病结局，这些数据将作为本提案的一部分进行更新。我们还将使用其他数据库验证我们的评分，包括更新的NHANES数据和UVa儿科肥胖诊所的数据。我们希望使用这种实验设计来产生一个临床上可访问和可解释的MetS风险评分，可用于识别儿童在发展成人疾病相关的MetS，谁可以有针对性地增加干预的风险较高。

DESCRIPTION (provided by applicant): Development of a childhood metabolic syndrome risk score for predicting adult disease. Project summary: The metabolic syndrome describes a group of medical findings that appear to be linked by an underlying process that increases risk for diabetes and heart disease. The best way to diagnose the metabolic syndrome in children remains unclear, though current attempts appear to result in racial/ethnic discrepancies. We propose to formulate a new race/ethnicity-specific MetS risk score for children by using known markers of disease risk as well as long-term information on the development of diabetes and heart disease. Children identified as having increased risk of adult disease could be targeted to receive increased efforts at prevention. PUBLIC HEALTH RELEVANCE: Development of a childhood metabolic syndrome risk score for predicting adult disease. Narrative: The metabolic syndrome (MetS) is a cluster of cardiovascular indices that appear to be linked by a poorly-understood insidious process that increases risk for Type 2 diabetes (T2DM) and coronary artery disease (CAD). These components of MetS include abdominal obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, and insulin resistance. The diagnosis of MetS is currently based on a combination of cut-off points for these different components. For children, there is not a consensus regarding which of several sets of pediatric MetS criteria to use clinically. Much of this uncertainty is related to the difficulty in linking long-term outcomes to a diagnosis of MetS, since children take a longer period of time to develop T2DM and CAD. Additionally, MetS criteria in adults have been shown to exhibit racial/ethnic discrepancies in their ability to predict T2DM and CAD. We propose to design a race/ethnicity-specific MetS risk score for children, using other serum factors known to be associated with long-term risk for adult coronary artery disease. These "surrogate" risk factors include fasting insulin, C-reactive protein, uric acid, and alanine aminotransferase. We will then validate and determine risk thresholds for this risk score, using longitudinal data that includes MetS information during childhood and adult outcomes data. Our plan is three-fold. We will first use the National Health and Nutrition Examination Survey (NHANES) to test current pediatric MetS criteria, with a hypothesis that we will demonstrate racial/ethnic discrepancies in the ability of current MetS criteria to predict elevations in our surrogates for adult disease. We will then use NHANES to design a race/ethnicity-specific pediatric MetS risk score, using elevations in our surrogates as a "target" and using linear regression to formulate this risk score using measurements of the components of MetS. Finally, we will validate this risk score and set thresholds that best predict long-term outcomes using the Lipid Research Clinic/Princeton Follow-up Study, with data from both childhood measurements of MetS and adult disease outcomes, which will be updated as part of this proposal. We will also validate our score using additional databases, including updated NHANES data and data from a pediatric obesity clinic at UVa. We expect to use this experimental design to produce a clinically accessible and interpretable MetS risk score that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for increased intervention.