METABOLIC EFFECT OF TRP64ARG MUTATION IN BETA 3 ADRENERGIC RECEPTORS IN DIABETES

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Investigators in Baylor College of Medicine and the Department of Human Genetics at the School of Public Health, Health Sciences Center, Houston, TX will study the effects of beta adrenergic receptor activation on lipid and glucose metabolism in Hispanic men and women with non-insulin-dependent diabetes mellitus (NIDDM). The objective of these studies is to determine whether there is a predictable relationship between the beta 3-adrenergic receptor (AR) mutation, body fat distribution and lipid and glucose metabolism in Mexican-Americans. By using nutrition and exercise as experimental manipulations, we plan to determine the role of this mutation in the regulation of fuel substrate metabolism in health and its dysregulation in NIDDM. Subjects will be identified among patients served in the Harris County Hospital District and the Starr County Health Studies in Southeast and South Texas. They will be characterized according to patterns in genomic DNA from leukocytes, body composition and distribution of abdominal fat using MRI, and plasma levels of glucose and insulin will be measured during fasting and after oral glucose administration. Approximately 850 subjects will be characterized in the cross-sectional study and 24 of these subjects will be studied more intensively using stable isotopic techniques under baseline, fed, fasting, resting, and exercising conditions. These studies in the 24 subjects will be repeated after one month of gradual weight reduction with the objective of decreasing body weight by 5 to 10 kg and reducing intraabdominal fat by 5% to 15%.