Excess abdominal visceral fat is associated with increased risk for coronary artery disease (CAD), Type 2 diabetes mellitus (DM), and hypertension. Although pre-menopausal women are largely protected against abdominal obesity, visceral fat accumulation increases after the menopause and there are concomitant deleterious changes in risk factors for CAD and Type 2 DM. Estrogen replacement attenuates increases in body weight and waist girth in postmenopausal women. However, it is not known whether estrogen use prevents or diminishes the visceral fat accumulation that occurs after menopause. It is possible that protective effects of estrogen on visceral fat metabolism contribute to the currently unknown component of the cardioprotective actions of estrogens.
The specific aims of the proposed studies are to determine in postmenopausal women whether: 1) estrogen use augments reductions in visceral fat; 2) estrogen use attenuates increases in visceral fat; 3) changes in visceral adiposity are related to changes in whole body and regional resistance to the suppression of lipolysis by insulin and whether this relationship is altered by estrogens; and 4) changes in visceral adiposity are associated with changes in certain risk factors for CAD and Type 2 DM independent of an in addition to the effects of estrogen. An additional aim is to determine whether raloxifene exerts similar effects as estrogens on visceral fat. Faloxifene is a popular selective estrogen receptor modulator that is being promoted as a safer alternative to estrogen not only for its osteogenic effects but also for possible cardioprotective effects. To meet these aims, 108 healthy but overweight postmenopausal women, aged 50- 60 years, will be randomly assigned a placebo, estrogen, and weight reduction program and subsequent increases in adiposity will be measured through a 12-month follow-up period during which time the hormone/drug treatment will continue. Changes in risk factors for CAD and Type 2 DM (blood lipids and lipoproteins, glucose tolerance, insulin resistance) in response to reductions and gains in visceral adiposity will be measured. Because insulin resistance is a prominent characteristic of abdominal obesity, the effects of estrogen/raloxifene and of changes in visceral, adiposity on the glucoregulatory and anti-lipolytic actions of insulin will be evaluated during hyper-insulinemic, euglycemic clamp procedures.
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