Consequences and Treatment of Growth Hormone Deficiency in the Metabolic Syndrome

描述（由申请方提供）：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生。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，估计该综合征影响约6000万美国人，或约20-30%的美国人口。代谢综合征是一种胰岛素抵抗和慢性炎症状态，表现为炎症性脂肪细胞因子水平升高，包括TNF-α和IL-6，其有助于增加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肥胖增加，因此可能具有降低的生长激素（GH）水平。生长激素缺乏症（GHD）可能通过影响胰岛素抵抗、炎症标志物和其他机制独立地导致心血管风险增加。尽管有数据表明，相对生长激素缺乏症是普遍存在于内脏肥胖患者和越来越多的数据表明生长激素缺乏症和心血管疾病之间的联系，生长激素缺乏症的患病率和代谢综合征心血管疾病的贡献是未知的。在这项研究中，我们将确定GH缺乏症在代谢综合征中的患病率，以及GH缺乏症对IMT增加和内皮功能障碍（心血管疾病的标志物）的贡献。基于初步数据，我们假设生长激素（GH）水平降低代谢综合征与过度内脏肥胖和代谢综合征和生理性GH缺乏症的患者，炎症心血管指标和颈动脉IMT将增加，表明增加动脉血管疾病。随后，我们将测试使用一种新的策略，以恢复生理GH水平，减少炎症标志物和IMT在这一人群中，使用GH促分泌剂显示在糖尿病患者中是安全的，并在其他模型的中心性肥胖有效。铺设说明：这项拨款将研究低GH水平的常见程度，并有助于腹部脂肪患者的心脏风险增加，以及增加低GH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.