Morbid obesity Class III is rapidly increasing in the United States, especially among Black women. It is associated with substantial increased morbidity, mortality and health care costs. Only bariatric surgery has been a relatively successful therapy. We propose to study the relationship of adiponectin and leptin as well as ghrelin, insulin, glucose and lipoprotein particle distribution among 300 black and 300 white women ages 50-79 who are morbidly obese, body mass index (BMI) >40 and 300 black and 300 white women with BMI <20-39.9. Women are participants in the Observational Study of the Women's Health Initiative (WHI OS). We hypothesize that there are specific phenotypes within this morbidly obese population based on biochemical and anthropometric characteristics. Second, we will determine the relationship of these biochemical markers within this morbidly obese group to risk of coronary heart disease (CHD), 150 cases, over approximately 8+ years of follow up. This study will greatly enhance understanding of the characteristics and risks associated with Class III obesity, provide a better definition of phenotype for future genetic studies and for therapeutic interventions. The study will use the stored blood samples from the WHI OS. The study has been approved by the WHI Steering Committee and the National Heart, Lung, and Blood Institute. Preliminary analysis has shown that risk of CHD across BMI categories is similar in black and white women within BMI categories, waist circumference directly and hip circumference inversely is a determinant of risk of total mortality and CHD. Levels of physical activity are inversely related to obesity and higher levels of physical activity are associated with lower risk. Ghrelin is the major secretagogue of growth hormone and declines with increasing weight. We hypothesize that at high BMI, there are women with high ghrelin, higher hip circumference, greater physical activity, lower WC, higher adiponectin, more insulin secretion, lower LDL and small LDL particles, higher HDL particles and lower risk of heart attack. We hypothesize further that the primary determinant of risk of heart attack will be distribution of lipoprotein particles, the determinants of lipoprotein particles are central obesity, insulin resistance, adiponectin, leptin and ghrelin. This will be the first epidemiology study to specifically focus on morbidly obesity Class III unselected for weight reduction, i.e. bariatric surgery, in black and white women. ? ? ?
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