GH, Cardiovascular Risk and Visceral Adiposity in Women

描述（由申请人提供）：流行病学研究清楚地表明，腹部或内脏脂肪较多的患者患心血管疾病的风险明显高于体脂优先积聚在臀股区域的患者。与内脏肥胖相关的动脉粥样硬化异常包括炎症性心血管危险标志物、血脂异常和胰岛素抵抗的增加。在发达国家，心血管疾病是导致死亡和疾病的主要原因。因此，研究内脏肥胖患者心血管风险增加的可能机制至关重要，开发这种疾病的潜在治疗方法也至关重要。由于垂体功能低下，生长激素（GH）缺乏的男性和女性内脏肥胖和心血管风险增加。研究已经基本确定生长激素分泌减少是这类患者内脏性肥胖和心血管疾病的独立危险因素。研究显示，在垂体功能低下导致的生长激素缺乏的女性中，给药生长激素可以减少内脏脂肪，但心血管风险标志物尚未被研究，在没有垂体疾病的情况下，由于肥胖导致的生长激素缺乏的男性和女性也未被研究。我们的初步数据表明，在没有垂体疾病的超重正常女性中，生长激素缺乏、躯干肥胖和心血管风险标志物增加之间存在很强的关联。这与有限的已发表的研究一致，这些研究表明，在没有垂体疾病的情况下，病态肥胖的生长激素分泌可能比瘦弱的男性和女性减少。在本研究中，我们将通过一项双盲、随机、安慰剂对照的研究方案，研究低剂量生长激素是否能在降低内脏脂肪量的同时，改善心血管风险指标，同时降低内脏脂肪量。

DESCRIPTION (provided by applicant): Epidemiologic studies have clearly demonstrated that patients with a preponderance of abdominal or visceral adiposity are at profoundly higher risk for cardiovascular disease than those with preferential accumulation of body fat in the gluteofemoral region. Atherogenic abnormalities associated with visceral adiposity include increases in inflammatory cardiovascular risk markers, dyslipidemia and insulin resistance. Cardiovascular disease is the leading cause of death and illness in developed countries. Therefore, the investigation of possible mechanisms underlying the increased cardiovascular risk in patients with visceral adiposity is critical, as is the development of potential therapies for this disorder. An elevated risk of visceral adiposity and cardiovascular risk has been established in men and women with growth hormone (GH) deficiency due to hypopituitarism. Studies have been fundamental in establishing that decreased GH secretion is an independent risk factor for visceral obesity and cardiovascular disease in such patients. GH administration has been shown to decrease visceral adiposity in women with GH deficiency due to hypopituitarism, but cardiovascular risk markers have not been studied, nor have men and women with GH deficiency due to obesity in the absence of pituitary disease. Our preliminary data suggest a strong association between GH deficiency, truncal adiposity and increased cardiovascular risk markers in overweight normal women without pituitary disease. This is consistent with limited published studies suggesting that GH secretion may be reduced in morbidly obese compared with lean men and women in the absence of pituitary disease. In this proposal, we will investigate, in a double-blind, randomized, placebo-controlled protocol whether low-dose GH administration improves markers of cardiovascular risk in parallel with reductions in visceral fat mass in the normal men and women with visceral adiposity and diminished GH secretion.