EXERCISE CAPACITY IN PEDIATRIC OBESITY AND TYPE 2 DIABETES

这个子项目是众多研究子项目之一

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.