CLINICAL TRIAL: DIETARY MACRONUTRIENT INTAKE AND EXERCISE ON GLUCOSE AND INSULIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在过去的30年里，美国超重儿童(6-19岁)的患病率(BMI和GT；95百分位数)增加了3倍，1999年达到13-14%。伴随着儿童超重的增加，儿童(0-19岁)2型糖尿病的发病率增加了4倍。虽然肥胖相关的糖代谢障碍的病因是多因素的，但饮食中大量营养素的摄入量和体力活动是潜在的重要因素。这项建议的目的是在健康的青少年中确定1)肥胖对能量消耗和底物氧化、糖异生和糖原分解产生的葡萄糖、胰岛素分泌和敏感性以及脂肪分解的影响；2)12周的适度运动计划是否会改善肥胖青少年的葡萄糖代谢，如果是，3)运动效果是否与心肌细胞内脂肪含量的减少和/或脂质氧化增加有关，以及4)饮食中的常量营养素构成是否影响运动的代谢效果。为了解决这些问题，将对24名超重(体脂30%)和24名非肥胖(体脂26%)青少年进行三次研究(在12周锻炼计划开始前、计划开始后6周和锻炼的最后一周期间)；在24名受试者中，12名肥胖者和12名非肥胖者在三次研究之前，每一次都将先进行7天的高碳水化合物饮食，而在另外24次研究中，将进行7天的高脂肪饮食。将使用最先进的稳定同位素-GCMS技术、磁共振成像和24小时室内量热法来获得实现上述目标所需的数据。这些研究提供的信息将提高我们对肥胖对青少年代谢影响的理解，并将导致识别可能增加2型糖尿病风险或预防或延缓青少年2型糖尿病发展的因素。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Over the past 30 years the prevalence of overweight children (6-19 y) in the USA (BMI>95th percentile) has increased 3-fold to reach 13-14% in 1999. Concomitant with the increase in childhood overweight, the incidence of type 2 diabetes in children (0-19 y) has increased 4-fold. Although the etiology of obesity related impairment of glucose metabolism is multifactorial, dietary macronutrient intake and physical activity are potentially important factors. The aims of this proposal are to determine in healthy adolescents 1) the impact of obesity on energy expenditure and substrate oxidation, glucose production from gluconeogenesis and glycogenolysis, insulin secretion and sensitivity and lipolysis; 2) whether a 12 weeks moderate exercise program will improve glucose metabolism in obese adolescents, and if so, 3) whether the exercise effect is correlated with a decrease in intramyocellular fat content and/or increased lipid oxidation, and 4) whether dietary macronutrient composition of the diet impacts metabolic effects of exercise. To address these questions, 24 over weight (body fat >30%) and 24 non-obese (body fat <26%) adolescents will be studied on three occasions (just prior to the start of a 12 weeks exercise program, 6 weeks into the program and during the last week of exercise); in 24 subjects,12 obese and 12 non-obese, each of the three study occasions will be preceded by 7-d of a high carbohydrate diet, and in the other 24 of a 7-d high fat diet. State of the art stable isotope-GCMS techniques, MRI and 24 h room calorimetry will be used to obtain the data needed to address the aims stated above. The information provided by these studies will improve our understanding of the metabolic effects of obesity in adolescents and will lead to identifying factors, which may increase the risk of type 2 diabetes or prevent or delay the development of type 2 diabetes in adolescents.