Cardiovascular Risk and Insulin Resistance: Age 7-40

描述(申请人提供)：这项研究申请将使用已经建立的队列，在父母(第一代)和他们的孩子(第二代)之间的跨代研究中，调查肥胖、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。基本的假设是，早期肥胖和胰岛素抵抗会导致心血管风险的发展，而通过与父母分享遗传和环境因素，儿童患2型糖尿病和动脉粥样硬化性心血管疾病的风险分布相似。我们可以接触到一群人，这些人最初是在童年早期被招募的，随后是青春期和成年期，目前他们的孩子的年龄与他们第一次被招募时的年龄相同，这为检验这一假设提供了一个独特的机会。这项应用的主要目的是通过比较父母(第一代，当他们还是孩子时和他们现在的成年年龄)和他们的孩子(第二代)的结果，将个人心血管危险因素(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)、炎症指标、脂肪细胞因子、氧化应激、血管研究和胰岛素抵抗的特定指标(正常血糖高胰岛素钳)在不同世代之间联系起来。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，这项研究将证明，在当前流行肥胖症和2型糖尿病(T2 DM)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。确定父母和孩子之间心血管风险因素的相似性，并确定预测哪些孩子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.