A mutation in the beta-3-adrenergic receptor gene (Trp64Arg), commonm in many ethnic populations, has an association with early onset of non-insulin dependent diabetes mellitus, elevated insulin levels, increased body mass index, and other features of the insulin resistance syndrome. To better characterize the physiology of these alterations, we will study the differences in glucose metaboilism, body composition, and energy expenditure in : 1) individuals with two copies of the normal allele, 2)individuals with two copies with the variant allele, and 3) individuals who are heterozygous for the variant receptor. We will determine the body composition using CT sacns for visceral fat measurements, anthropometric measurements, and DEXA scans to determine fat mass. Glucose tolerance will be determined using IV glucose tolerance tests to measure acute insulin response to glucose (AIRg) (insulin secreted in the first 10 minutes after a standardized glucose bolus), insulin sensitivity index (S1), and insulin disposition index (S1 x AIRg) using minimal model analysis. Energy expenditure will be determined using indirect calorimetry and doubly-labeled water method, and compared among the three groups. Individual measurements will be collated in to a database and quantitative traits will be compared among the three groups by analysis of variance, and where appropriate, analysis of covariance.
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