Cardiovascular Risk and Insulin Resistance: Age 7-40

描述（由申请人提供）：本研究申请将使用一个已经建立的队列，在父母（第1代）（我们对他们从7岁到40岁进行了长期重复观察）和他们的孩子（第2代）之间的跨代研究中研究肥胖、胰岛素抵抗的早期发展及其与相关心血管（CV）风险因素的相互作用。潜在的假设是，早期肥胖和胰岛素抵抗驱动CV风险的发展，儿童通过与父母共享遗传和环境因素，表现出2型糖尿病和动脉粥样硬化CV疾病发展的相似风险特征。我们访问了一组最初在幼儿期被招募的个体，随后是青春期和青年期，目前他们的孩子年龄与他们第一次被招募时的年龄相当，这为检验这一假设提供了一个独特的机会。本申请的主要目的是关联个体CV风险因素（高胰岛素血症、血压、肥胖、血脂）、生活方式行为、内脏脂肪（腹部CT）、炎症指标、脂肪细胞因子、氧化应激、血管研究和胰岛素抵抗的具体指标通过比较父母的发现，（第1代，当他们是儿童时，在他们目前的成年年龄）与他们的孩子（第2代）。显性心血管疾病在儿童中很少见，但与其发展相关的因素在生命早期就存在。因此，本研究将记录的重要性，在这个流行性肥胖症和2型糖尿病（T2DM）的时代，确定高风险的家庭和儿童，以便在疾病发展之前引入有效的干预策略。描述父母及其子女之间CV风险要素的相似性，并确定预测哪些儿童有代谢和心血管并发症风险的标志物，是实现这一临床科学目标的初始步骤。

DESCRIPTION (provided by applicant): This research application will use an already established cohort to investigate the early development of obesity, insulin resistance, and their interaction with associated cardiovascular (CV) risk factors in a cross- generational study between parents (generation 1), on whom we have long-term repeated observations from age 7 to 40, and their children (generation 2). The underlying hypotheses are that early adiposity and insulin resistance drive the development of CV risk and that children, by sharing genetic and environmental factors with their parents, exhibit a similar risk profile for development of type 2 diabetes and atherosclerotic CV disease. Our access to a cohort of individuals who were initially recruited in early childhood, followed through adolescence and young adulthood and currently have children equivalent in age to their own age when they were first recruited, offers a unique opportunity to test this hypothesis. The major objective of this application is to relate individual CV risk factors (hyperinsulinemia, blood pressure, obesity, lipids), lifestyle behaviors, visceral fat (abdominal CT), measures of inflammation, adipocytokines, oxidative stress, vascular studies, and specific measures of insulin resistance (euglycemic hyperinsulinemic clamps) between generations by comparing findings in the parents (generation 1, when they were children and at their current adult age) with their children (generation 2). Overt cardiovascular disease is rare in children, but the factors associated with its development are present early in life. Thus, this study will document the importance, in this current era of epidemic obesity and type 2 diabetes mellitus (T2DM), of identifying high-risk families and children in order to introduce effective intervention strategies prior to disease development. Delineation of similarities in the elements of CV risk between parents and their children and identification of markers that predict which children are at risk for metabolic and cardiovascular complications are the initial steps to achieve this clinical scientific goal.