Consequences and Treatment of Growth Hormone Deficiency in the Metabolic Syndrome

描述（由申请人提供）：代谢综合征的特征是中枢性肥胖增加、血脂异常、血压升高和胰岛素抵抗，所有这些都可能导致心血管疾病的发展。代谢综合征是一个重大的公共卫生问题。代谢综合征的患病率正在增加，据估计，该综合征影响了大约6000万美国人，约占美国人口的20-30%。代谢综合征是一种胰岛素抵抗和慢性炎症的状态，表现为炎症性脂肪细胞因子水平升高，包括tnf - α和IL-6，它们有助于增加c反应蛋白（CRP）、内皮功能障碍和心血管疾病。代谢综合征患者表现为腹部脂肪增加，因此可能有生长激素（GH）水平降低。生长激素缺乏（GHD）可能通过对胰岛素抵抗、炎症标志物和其他机制的影响而独立地增加心血管风险。尽管有数据表明相对生长激素缺乏在内脏型肥胖患者中普遍存在，并且越来越多的数据表明生长激素缺乏与心血管疾病之间存在联系，但生长激素缺乏在代谢综合征中对心血管疾病的患病率和贡献尚不清楚。在这项资助中，我们将确定生长激素缺乏症在代谢综合征中的患病率，以及生长激素缺乏症对IMT增加和内皮功能障碍（心血管疾病的标志）的贡献。基于初步数据，我们假设代谢综合征中生长激素（GH）水平降低与内脏过度肥胖有关，代谢综合征和生理性GH缺乏的患者炎症性心血管指数和颈动脉IMT升高，表明动脉硬化性血管疾病增加。随后，我们将测试使用一种新的策略来恢复生理性生长激素水平，降低这一人群的炎症标志物和IMT，使用一种生长激素分泌剂，这种激素在糖尿病患者中是安全的，在其他中枢性肥胖模型中是有效的。Lay Description：这项拨款将研究低生长激素水平是如何普遍出现的，以及对腹部脂肪患者心脏风险增加的影响，以及增加低生长激素水平是否会改善这一人群的心脏风险。

DESCRIPTION (provided by applicant): Metabolic syndrome is characterized by an increase in central adiposity, abnormal lipid profile, elevated blood pressure, and insulin resistance, all of which may contribute to the development of cardiovascular disease. Metabolic syndrome is a major public health problem. The prevalence of metabolic syndrome is increasing and the syndrome is estimated to affect approximately 60 million Americans, or about 20-30% of the American population. Metabolic syndrome is a state of insulin resistance and chronic inflammation, as reflected by elevated levels of inflammatory adipocytokines, including TNF-alpha and IL-6 which contribute to increase C-reactive protein (CRP), endothelial dysfunction and cardiovascular disease. Patients with metabolic syndrome present with increased abdominal adiposity and therefore may have reduced growth hormone (GH) levels. GH deficiency (GHD) may contribute independently to increased cardiovascular risk through effects on insulin resistance, inflammatory markers and other mechanisms. Despite data suggesting that relative GH deficiency is prevalent in viscerally obese patients and increasing data suggesting a link between GH deficiency and cardiovascular disease, the prevalence and contributions of GH deficiency to cardiovascular disease in the metabolic syndrome is not known. In this grant we will determine the prevalence of GH deficiency in the metabolic syndrome, and the contribution of GH deficiency to increased IMT and endothelial dysfunction, markers of cardiovascular disease. Based on preliminary data, we hypothesize that growth hormone (GH) levels are reduced in metabolic syndrome in association with excess visceral adiposity and that among patients with metabolic syndrome and physiologic GH deficiency, inflammatory cardiovascular indices and carotid IMT will be increased, indicating increased arteriosclerotic vascular disease. We will subsequently test the use of a novel strategy to restore physiologic GH levels and reduce inflammatory markers and IMT in this population, using a GH secretogogue shown to be safe in patients with diabetes and effective in other models of central obesity. Lay Description: This grant will study how commonly low GH level are seen and contribute to increased cardiac risk in patients with abdominal fat and whether increasing low GH levels will improve cardiac risk in this population.