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来调查肥胖、胰岛素抵抗的早期发展，以及它们与相关心血管（CV）危险因素的相互作用，这是一项跨代研究，研究对象是父母（第一代）和他们的孩子（第二代），我们对他们进行了从7岁到40岁的长期重复观察。潜在的假设是，早期肥胖和胰岛素抵抗驱动心血管风险的发展，儿童通过与其父母共享遗传和环境因素，表现出类似的2型糖尿病和动脉粥样硬化性心血管疾病的发展风险概况。我们对一群人进行了研究，这些人最初是在幼儿时期被招募的，一直到青春期和青年期，目前他们的孩子的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。本应用程序的主要目的是通过比较父母（第一代、第一代、第一代、第一代）的发现，将个体CV危险因素（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）、炎症测量、脂肪细胞因子、氧化应激、血管研究和胰岛素抵抗的特定测量（正糖高胰岛素钳）联系起来。当他们还是孩子的时候，在他们现在成年的时候，和他们的孩子（第二代）在一起。明显的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，本研究将证明，在当今肥胖和2型糖尿病（T2DM）流行的时代，识别高危家庭和儿童的重要性，以便在疾病发展之前引入有效的干预策略。描述父母和子女之间心血管风险因素的相似性，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第一步。

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.