EXERCISE CAPACITY IN PEDIATRIC OBESITY AND TYPE 2 DIABETES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。2型糖尿病（T2DM）在美国成人和青少年人群中的流行比例都在增加。运动对于预防和治疗2型糖尿病至关重要。然而，成年T2DM患者的运动能力较差，这可以通过最大和次最大运动表现的降低来衡量。这一发现是正确的，即使将患有2型糖尿病的成年人与同样久坐和同样肥胖的对照组进行比较。因此，除了身体不适和肥胖之外，糖尿病还有其他因素，使这些人更难锻炼。这种运动缺陷可能由内皮功能异常、心脏舒张功能异常、骨骼肌脂质沉积、炎症和/或胰岛素抵抗本身来解释。目前还没有关于青少年2型糖尿病患者的运动能力是否已经受损的研究，也没有评估运动功能关键成分异常的研究（内皮功能、心脏舒张功能、骨骼肌脂质含量或胰岛素抵抗本身的影响）。然而，我们的初步研究表明，青少年糖尿病患者的运动功能下降。因此，本研究的目的是首先评估青少年2型糖尿病患者的运动功能，通过在自行车测力器上运动时测量Vo2 max和Vo2动力学。这些受试者将与同样活跃的瘦人对照组和肥胖者对照组进行比较，以独立检查肥胖和不运动的影响。此外，次要结果将包括胰岛素敏感性（通过高胰岛素正糖钳）、内皮功能（通过肱动脉超声和容积描记术）、舒张功能（通过运动超声心动图）和感知运动（通过博格量表）的测量。此外，结果将与身体组成（腰围、臀围和双能x线吸收测量）、炎症测量（c肽、c反应蛋白、IL-6和髓过氧化物酶）、肝脏炎症测量（丙氨酸氨基转移酶）、血脂（游离脂肪酸和空腹血脂）和脂联素相关。通过明确青少年2型糖尿病患者存在的运动缺陷，并检查潜在的原因，我们希望改进儿童糖尿病的运动治疗方法，帮助预防运动缺陷的发生或发展。

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. Type 2 diabetes (T2DM) is increasing in epidemic proportions among both adult and adolescent populations in the United States. Exercise is critical to both the prevention and treatment of T2DM. However, adults with T2DM are less able to exercise, as measured by reduced maximal and submaximal exercise performance. This finding holds true, even when adults with T2DM are compared to equally sedentary and equally obese controls. Therefore, there is something about the diabetes, beyond deconditioning and obesity, that makes it more difficult for such people to exercise. This exercise defect may be explainable by abnormal endothelial function, abnormal diastolic heart function, lipid deposition in skeletal muscle, inflammation, and/or the insulin resistance itself. There are currently no studies looking at whether adolescents with type 2 diabetes already have impairment in their ability to exercise, nor are there studies assessing abnormalities in components critical to exercise function (endothelial function, diastolic heart function, skeletal muscle lipid content, or the effects of insulin resistance itself). Our preliminary study indicates, however, that exercise function is reduced in adolescents with diabetes. Therefore, the goal of this study is to first assess exercise function, as measured by Vo2 max and Vo2 kinetics while exercising on a bicycle ergometer, in adolescents with type 2 diabetes. These subjects will be compared to similarly active lean and obese controls, to independently examine the effects of obesity and inactivity. In addition, secondary outcomes will include measurement of insulin sensitivity (by hyperinsulinemic euglycemic clamp), endothelial function (by brachial artery ultrasound and plethesmography), diastolic function (by echocardiogram with exercise), and perceived exertion (by Borg Scale). In addition, outcomes will be correlated with body composition (waist:hip circumference and dual energy x-ray absorptiometry), measures of inflammation (c-peptide, c-reactive protein, IL-6, and myeloperoxidase), measures of liver inflammation (alanine amino transferase), serum lipids (free fatty acids, and fasting lipid profile) and adiponectin. By defining the exercise defects present in adolescents with T2DM, and examining potential causes, we hope to improve the exercise treatment approach to pediatric diabetes and help prevent exercise defects from occurring or progressing.