Postprandial Glycemia in Association with Vascular Disease in Childhood Obesity

餐后血糖与儿童肥胖血管疾病的关系

• 批准号: 7076371
• 负责人: TANIA BURGERT
• 金额: $ 12.74万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076371
• 关键词: adolescence (12-20); biomarker; blood glucose; cardiovascular disorder; cardiovascular disorder risk; cardiovascular function; chemoprevention; clinical research; glucose tolerance test; human puberty; human subject; human therapy evaluation; hyperglycemia; hypoglycemic agents; obesity; patient oriented research; vascular endothelium; vasodilation

DESCRIPTION (provided by applicant): The detrimental health consequences of childhood obesity are evident in the emergence of "adult" diseases such as pre-diabetes, the metabolic syndrome and type 2 diabetes mellitus in today's youth. Disconcerting is that in adults, each of these conditions is strongly predictive of cardiovascular mortality. Still little is known about the vascular health of obese children and to which extend the early metabolic consequences of adiposity are toxic to the vasculature. Preliminary data by the candidate and recent studies in adults, suggest that exaggerated post-prandial glycemia may be injurious to the vasculature, even in ranges below the diagnostic cut-off for pre-diabetes. Therefore, the overall objective of this proposal is to determine whether increases in meal-stimulated glucose excursions in obese youth are related to physiologic measures and biomarkers of vascular toxicity. The Candidate is a junior faculty member in the Section of Pediatric Endocrionolgy at the Yale University. Her long term career goal is to become an independent investigator in childhood obesity and diabetes with the ultimate goal of impacting the metabolic/cardiovascular consequences of childhood obesity. Yale University's longstanding history in pediatric obesity and diabetes research places the candidate in a strong position to accomplish this task. Dr. Burgert will be mentored by Dr. Sonia Caprio and Dr. William Tamborlane, two highly accomplished investigators in this field, who are all committed to her success. This K-23 application will focus on examining the relationship between post-prandial glucose exposure (as assessed by OGTT and the Medtronic MiniMed continuous glucose monitoring system) and biomarkers of vascular health in a large cohort of non-diabetic obese youth. Non-invasive techniques will be used to assess endothelial function of vasculature such as peripheral arterial tonometry (PAT) and flow mediated vasodilation of the brachial artery FMD). The second aim will determine whether attenuation of postprandial glycemia leads to improvement in cardiovascular risk profile and vascular function. To this end a double blind placebo controlled intervention study with acarbose will be performed in a select group of subjects. Results of such an intervention study will provide important preliminary data for future large-scale treatment studies directed at improving cardiovascular health by reversing early metabolic abnormalities in obese children.

描述（由申请人提供）： 儿童肥胖的不利健康后果在当今年轻人的“成人”疾病的出现中显而易见。令人不安的是，在成年人中，这些条件中的每一个都在强烈预测心血管死亡率。关于肥胖儿童的血管健康以及扩展肥胖的早期代谢后果对脉管系统的毒性仍然知之甚少。候选人的初步数据和最新的成人研究表明，即使在糖尿病前期诊断性临界值的范围内，夸张的后血糖也可能对脉管系统有害。因此，该提案的总体目的是确定肥胖青年中饮食中葡萄糖偏移的增加是否与血管毒性的生理测量和生物标志物有关。候选人是耶鲁大学小儿内co骨科的初级教师。她的长期职业目标是成为儿童肥胖症和糖尿病的独立研究者，其最终目标是影响儿童肥胖症的代谢/心血管后果。耶鲁大学在儿科肥胖和糖尿病研究方面的长期历史使候选人处于完成这项任务的强烈地位。 Burgert博士将由Sonia Caprio博士和William Tamborlane博士进行指导，他们是该领域的两位高度成就的调查员，他们都致力于她的成功。该K-23的应用将着重于研究派葡萄糖暴露的关系（如OGTT和Medtronic最小化的连续葡萄糖监测系统评估）和在大量非糖尿病肥胖青年中的血管健康生物标志物。非侵入性技术将用于评估脉管系统的内皮功能，例如外周动脉沟通（PAT）和流动介导的臂动脉FMD的血管舒张）。第二个目的将决定餐后血糖的衰减是否会改善心血管风险概况和血管功能。为此，将在一组受试者中进行一项双重安慰剂对照干预研究。这种干预研究的结果将为未来的大规模治疗研究提供重要的初步数据，该研究旨在通过逆转肥胖儿童的早期代谢异常来改善心血管健康。