Metabolic Markers and Predictors of Childhood Obesity

儿童肥胖的代谢标志物和预测因子

• 批准号: 6738140
• 负责人: SONIA CAPRIO
• 金额: $ 25.75万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6738140
• 关键词: African American; Hispanic Americans; adolescence (12-20); biomarker; blood chemistry; body composition; calorimetry; caucasian American; clinical research; comorbidity; disease /disorder proneness /risk; glucose clamp technique; human subject; human therapy evaluation; hyperinsulinism; insulin sensitivity /resistance; lipid metabolism; metformin; middle childhood (6-11); noninsulin dependent diabetes mellitus; nuclear magnetic resonance spectroscopy; nutrition disorder chemotherapy; obesity; patient oriented research; racial /ethnic difference

DESCRIPTION (provided by applicant): Juvenile obesity is the most prevalent nutritional disease in the U.S. This proposal seeks continued support of a project funded since 1991, which focuses on the identification of early metabolic disturbances implicated in the pathogenesis of juvenile obesity. The studies proposed here are natural extensions of our previous work in this area. The focus of this application is to understand the mechanisms responsible for the insulin resistance associated with juvenile obesity. The central hypothesis of this renewal is that insulin resistance and hyperinsulinemia favor weight gain and lead to the associated metabolic complications of juvenile obesity. Thus, interventions that target insulin resistance may not only control weight gain but also prevent the metabolic complications of juvenile obesity. The specific aims are: 1) to determine whether ethnic differences in insulin sensitivity are related to greater intramyocellular (IMCL) accumulations of lipid content in obese adolescents of African American and Hispanic origin, compared to Caucasian adolescents closely matched for overall adiposity; 2) to determine longitudinal changes in circulating adiponectin levels in relation to changes in insulin sensitivity during the development of juvenile obesity; and 3) to determine whether interventions--such as the use of metformin, a biguanide--can enhance insulin sensitivity and decrease hyperinsulinemia, which will lead to a reduction in weight gain and improvement in cardiovascular risk factors in obese adolescents. The combination of whole body metabolic methods (glucose clamps, stable isotope kinetics and indirect calorimetry), together with sequential measurements of the novel adipose-specific protein adiponectin and the use of 1H-NMR spectroscopy to assess non-invasively, for the first time, IMCL lipid stores in children, will provide the unique opportunity to advance the understanding of the mechanisms underlying the insulin resistance in childhood obesity.

描述(申请人提供)：青少年肥胖是美国最常见的营养疾病。这项提案寻求对1991年以来资助的一个项目的持续支持，该项目的重点是识别与青少年肥胖的发病机制有关的早期代谢障碍。这里提出的研究是我们以前在这一领域工作的自然延伸。这项应用的重点是了解与青少年肥胖相关的胰岛素抵抗的机制。这一更新的中心假设是胰岛素抵抗和高胰岛素血症有利于体重增加，并导致青少年肥胖的相关代谢并发症。因此，针对胰岛素抵抗的干预措施不仅可以控制体重增加，还可以预防青少年肥胖的代谢并发症。研究的具体目的是：1)确定与总体肥胖率相近的高加索青少年相比，非裔美国人和西班牙裔肥胖青少年的胰岛素敏感性种族差异是否与其心肌内脂肪含量(IMCL)更高有关；2)确定循环脂联素水平的纵向变化与青少年肥胖发展过程中胰岛素敏感性的变化；以及3)确定干预措施--如使用双胍类药物二甲双胍--是否可以增强胰岛素敏感性和降低高胰岛素血症，从而减少肥胖青少年的体重增加和心血管危险因素的改善。结合全身代谢方法(葡萄糖钳、稳定同位素动力学和间接量热法)，以及对新型脂肪特异性蛋白质脂联素的连续测量，以及首次使用1H-核磁共振波谱对儿童IMCL脂肪储存进行无创性评估，将提供独特的机会，促进对儿童肥胖胰岛素抵抗机制的理解。