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）： 儿童肥胖对健康的不利影响在当今年轻人中出现的“成人”疾病（例如糖尿病前期、代谢综合征和 2 型糖尿病）中显而易见。令人不安的是，在成年人中，上述每一种情况都强烈预示着心血管死亡率。关于肥胖儿童的血管健康仍然知之甚少，并且肥胖的早期代谢后果对脉管系统是有毒的。候选人的初步数据和最近对成人的研究表明，餐后血糖过高可能会对脉管系统造成损害，即使在低于糖尿病前期诊断临界值的范围内也是如此。因此，该提案的总体目标是确定肥胖青少年中膳食刺激的血糖波动的增加是否与血管毒性的生理测量和生物标志物有关。候选人是耶鲁大学儿科内分泌科的初级教员。她的长期职业目标是成为儿童肥胖和糖尿病的独立研究者，最终目标是影响儿童肥胖的代谢/心血管后果。耶鲁大学在儿童肥胖和糖尿病研究方面的悠久历史使候选人在完成这项任务方面处于有利地位。 Burgert 博士将得到 Sonia Caprio 博士和 William Tamborlane 博士的指导，他们是该领域两位卓有成就的研究人员，他们都致力于帮助她取得成功。该 K-23 应用程序将重点检查大量非糖尿病肥胖青年的餐后葡萄糖暴露（通过 OGTT 和美敦力 MiniMed 连续血糖监测系统评估）与血管健康生物标志物之间的关系。非侵入性技术将用于评估脉管系统的内皮功能，例如外周动脉张力测定（PAT）和肱动脉血流介导的血管舒张（FMD）。第二个目标将确定餐后血糖的减弱是否会导致心血管风险状况和血管功能的改善。为此，将在选定的受试者组中进行阿卡波糖的双盲安慰剂对照干预研究。此类干预研究的结果将为未来大规模治疗研究提供重要的初步数据，这些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。