The incidence of type 2 diabetes in adolescents is increasing, and this increase is disproportionate in Hispanics and African Americans. In addition, the rise in minority obesity in youth is associated with progressive insulin resistance and risk factors for cardiovascular disease. Although the exact cause for these trends are not known, it is clear that they are closely related to the increase in obesity prevalence. However, it is not currently known why some obese subjects remain healthy and at low associated disease risk, while others appear at high disease risk and some develop type 2 diabetes. Two predominant paradigms, both based on an abnormal accumulation of body fat, have been used to explain the reasons why some obese subjects develop insulin resistance, diabetes, and cardiovascular risk, while others do not. Project 2 will examine these possible theories. The first possibility is the portal/visceral hypothesis, which suggests an abnormal accumulation of visceral adipose tissue. The second possibility is the ectopic fat storage hypothesis, which suggests an abnormal accumulation of ectopic fat in liver, skeletal muscle and possibly the pancreas. In Project 2, we will measure intraabdominal, hepatic, pancreatic and muscular fat accumulation, and characterize intramuscular lipid composition in Hispanic, African American and Caucasian adolescents who are either lean, obese with normal glucose tolerance, obese with impaired glucose tolerance (IGT), or patients with type 2 diabetes. Regional fat deposition and composition will be assessed using state-of-the-art magnetic resonance imaging and spectroscopy. We will also employ high-resolution ultrasound to measure carotid intima-medial thickness as a surrogate for vascular fat deposition and for the risk of cardiovascular disease in these populations. Our hypotheses are: 1) Fat deposition (intraabdominal, hepatic, pancreatic and muscular fat), intramuscular levels of saturated fatty acids, and measures of carotid wall thickness will increase with degree of disease progression (lean -? obese ->pre-diabetes (obese+IGT) ? diabetes);2) At each degree of disease progression, fat deposition, the ratio of saturated-to-unsaturated fatty acid, and carotid wall thickness will be higher in Hispanic and African American subjects when compared with Caucasian subjects, even after adjusting for total body fat;and, 3) Measures of fat deposition and composition at the various sites will allow the identification of unique fat phenotypes related to differences in disease risk between Hispanic, African American and Caucasian populations. In summary, Project 2 will utilize an array of advanced imaging techniques to conduct a comprehensive analysis of the patterns of body fat deposition across the spectrum of obesity-related disease progression in minority youth.
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