GH, Cardiovascular Risk and Visceral Adiposity in Women

描述（由申请人提供）：流行病学研究已明确表明，腹部或内脏肥胖占优势的患者发生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性心血管风险标志物、血脂异常和胰岛素抵抗的增加。心血管疾病是发达国家死亡和疾病的主要原因。因此，调查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。由于垂体功能减退，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。研究已基本确定GH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。GH管理已被证明可以减少内脏肥胖的女性GH缺乏症由于垂体功能减退，但心血管风险标志物尚未研究，也没有男性和女性GH缺乏症由于肥胖在没有垂体疾病。我们的初步数据表明，生长激素缺乏症，躯干肥胖和心血管风险标志物增加超重正常妇女无垂体疾病之间有很强的关联。这与有限的已发表研究一致，这些研究表明，与无垂体疾病的瘦男性和女性相比，病态肥胖者的GH分泌可能减少。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GH给药是否能改善内脏脂肪增多和GH分泌减少的正常男性和女性的心血管风险标志物，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.