GH, Cardiovascular Risk and Visceral Adiposity in Women

描述(由申请人提供)：流行病学研究已经清楚地表明，腹部或内脏肥胖症占多数的患者患心血管疾病的风险比那些体脂优先聚集在臀部和股部的患者高得多。与内脏肥胖相关的动脉粥样硬化异常包括炎性心血管危险标记物增加、血脂异常和胰岛素抵抗。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，研究内脏肥胖症患者心血管风险增加的可能机制是至关重要的，开发这种疾病的潜在治疗方法也是至关重要的。由于垂体功能减退而导致生长激素(GH)缺乏的男性和女性患内脏肥胖症和心血管疾病的风险增加。研究表明，生长激素分泌减少是此类患者内脏肥胖和心血管疾病的独立危险因素，这一点是基本的。GH治疗已被证明可以降低因垂体功能减退所致的GH缺乏症患者的内脏肥胖症，但心血管风险标记物尚未被研究过，也没有研究过无垂体疾病的肥胖所致的GH缺乏症的男性和女性。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、躯干肥胖症和心血管风险标记物增加之间存在很强的相关性。这与发表的有限研究一致，这些研究表明，与没有脑垂体疾病的瘦男人和女人相比，病态肥胖者的生长激素分泌可能会减少。在这项建议中，我们将采用双盲、随机、安慰剂对照的方案，研究在内脏肥胖症和生长激素分泌减少的正常男性和女性中，小剂量GH给药是否在减少内脏脂肪质量的同时改善心血管风险标记物。

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.