Metabolic Markers and Predictors of Childhood Obesity

儿童肥胖的代谢标志物和预测因素

• 批准号: 7095250
• 负责人: SONIA CAPRIO
• 金额: $ 25.15万
• 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/7095250
• 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（由申请人提供）：少年肥胖症是美国最普遍的营养疾病，该提案寻求自1991年以来资助的项目的持续支持，该项目的重点是鉴定与青少年肥胖症发病机理有关的早期代谢性疾病。这里提出的研究是我们以前在该领域工作的自然扩展。该应用的重点是了解导致与少年肥胖相关的胰岛素抵抗的机制。这种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少年肥胖的代谢并发症。因此，靶向胰岛素抵抗的干预措施不仅可以控制体重增加，而且还可以防止少年肥胖的代谢并发症。具体目的是：1）确定胰岛素敏感性的种族差异是否与非洲裔美国人和西班牙裔肥胖青少年中脂质含量的较大细胞内（IMCL）积累有关，与白人青少年相比，脂肪的肥胖是整体肥胖的匹配。 2）确定循环脂联素水平的纵向变化，相对于少年肥胖过程中胰岛素敏感性的变化而言； 3）为了确定干预措施（例如使用二甲甲蛋白，biguanide）是否可以增强胰岛素敏感性并降低高胰岛素血症，这将导致肥胖青少年体重增加和心血管危险因素的改善。 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儿童肥胖症中的胰岛素抵抗。