Developing a Childhood Metabolic Syndrome Risk Score to Predict Adult Disease

描述(由申请人提供)： 用于预测成人疾病的儿童代谢综合征风险评分的发展。项目摘要：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了种族/民族差异。我们建议使用已知的疾病风险标记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/民族特定的METS风险评分。可以针对被确定为成人疾病风险增加的儿童进行更多的预防工作。 公共卫生相关性： 用于预测成人疾病的儿童代谢综合征风险评分的发展。简介：代谢综合征(METS)是一组心血管指标，似乎与一个知之甚少的潜伏过程有关，该过程增加了2型糖尿病(T2 DM)和冠状动脉疾病(CAD)的风险。蛋氨酸的这些成分包括腹型肥胖、高甘油三酯血症、低高密度脂蛋白胆固醇、高血压和胰岛素抵抗。目前对甲亢症的诊断是基于这些不同成分的截断点的组合。对于儿童，对于临床使用几套儿科METS标准中的哪一套，还没有达成共识。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成T2 DM和CAD。此外，成人的METS标准已被证明在预测T2 DM和CAD的能力方面显示出种族/民族差异。我们建议使用其他已知的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/民族特定的METS风险评分。这些“替代”危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时期的METS信息和成人结局数据的纵向数据来验证和确定该风险评分的风险阈值。我们的计划有三个方面。我们首先将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，假设我们将证明当前METS标准在预测我们的成人疾病代理人的水平方面存在种族/民族差异。然后，我们将使用NHANES来设计特定于种族/民族的儿科METS风险评分，使用我们的替代者的海拔作为“目标”，并使用线性回归来通过测量METS的组成部分来制定该风险评分。最后，我们将使用血脂研究诊所/普林斯顿大学的后续研究来验证这一风险评分，并设置最能预测长期结果的阈值，该研究使用儿童时期对METS和成人疾病结果的测量数据，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来验证我们的得分，包括更新的NHANES数据和来自UVA儿童肥胖诊所的数据。我们希望使用这一实验设计来产生临床可访问和可解释的METS风险评分，该评分可用于识别患有与METS相关的成人疾病的风险较高的儿童，然后可以针对他们进行更多干预。

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.