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Study for pathophysiological significance of growth hormone in adult men.

成年男性生长激素病理生理学意义的研究。

基本信息

批准号：
14571074
负责人：
TAKANO Kazue
金额：
$ 1.86万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

In this study, we have investigated pathophysiological significance of growth hormone in adult men as follows.1.Metabolic disorders in patients with adult growth hormone deficiency and acromegary.Clinical and biochemical data of patients with adult GHD(AGHD) and acromegaky who attended Tokyo Women's Medical University were analyzed retrospectively from medical records.In AGHD, diabetes mellitus and impaired glucose tolerance was found in 4 and 16% of the patients, respectively. Forty-two percent of the patients had hypercholesterolemia, 41% had hypertriglyceridemia, 55% had decreased levels of HDL cholesterol. Thirty-five % of the patients had body mass index(BMI) being>25 kg/m^2. Abnormal findings including increased Intima-media thickness(IMT) or plaque being observed in 27 and 20% of the patients. The homeostasis model insulin resistance index(HOMA-R) was 2.87±0.38, suggesting insulin resistance. These data suggest that abnormal lipid and glucose metabolism, and atherosclerotic chan … More ges occur frequently in adult patients with GHD. Insulin resistance may play a role in disorders of glucose and lipid metabolism associated with GHD.In patients with acromegaly, diabetes mellitus and impaired glucose tolerance was found in 45 and 33% of the patients, respectively. Acromegalics had high HOMA-R (3.59±0.56). Serum GH levels in the patients with DM were higher than those in NGT, but, serum IGF-I levels and SDS were not different among the groups. These data suggests that IGF-I might not play the role of glucose metabolism in these patients.2.Serum levels of adipocytokines in adult growth hormone deficiency and acromegalyAtherosclerosis and insulin resistance are common complications of adult growth hormone deficiency(GHD) and acromegaly. Circulating adiponectin, an adipocyte-derived protein, has both anti-atherogenic and insulin-sensitising effects. The values of QUICKI as insulin sensitivity index were significantly lower in patients with acromegaly or adult GHD compared to normal subjects (0.33±0.03,0.35±0.04,and 0.36±0.01,respectively). While patients with adult GHD had significantly lower serum adiponectin levels than patients with acromegaly (6.5±3.9,9.2±5.0,P<0.01) these levels were not significantly different from those found in normal subjects (7.8±4.3 μg/ml). There was an inverse correlation between serum adiponectin levels and BMI in both patient groups. However, serum adiponectin levels correlated positively with QUICKI (Rs=0.37,) only in patients with adult GHD. These results demonstrate that adiponectin levels are significantly lower in patients with adult GHD than in patients with acromegaly. Adiponectin levels are similar in patients with GHD and healthy controls, whereas in patients with acromegaly, insulin resistance appears to be not closely related to adiponectin levels compared with BMI. The different relationship between adiponectin and QUICKI observed in the adult GHD and acromegaly groups presumably reflects differences in the mechanisms of insulin resistance under states of GH deficiency or excess.Serum resistin levels were also investigated in patients with GHD and acromegaly. Less

在本研究中，我们对成年男性中生长激素的病理生理学意义进行了如下研究。 1.成人生长激素缺乏症和肢端肥大症患者的代谢紊乱。根据病历对东京女子医科大学就诊的成人GHD（AGHD）和肢端肥大症患者的临床和生化数据进行回顾性分析。分别有 4% 和 16% 的患者出现葡萄糖耐量。 42%的患者患有高胆固醇血症，41%的患者患有高甘油三酯血症，55%的患者HDL胆固醇水平降低。 35%的患者体重指数（BMI）>25 kg/m^2。 27% 和 20% 的患者观察到异常结果，包括内膜中层厚度 (IMT) 或斑块增加。稳态模型胰岛素抵抗指数(HOMA-R)为2.87±0.38，提示存在胰岛素抵抗。这些数据表明，成人 GHD 患者经常出现脂质和葡萄糖代谢异常以及动脉粥样硬化变化。胰岛素抵抗可能在与 GHD 相关的葡萄糖和脂质代谢紊乱中发挥作用。在肢端肥大症患者中，分别有 45% 和 33% 的患者患有糖尿病和糖耐量受损。肢端肥大药具有较高的 HOMA-R (3.59±0.56)。 DM患者血清GH水平高于NGT患者，但血清IGF-I水平和SDS在各组间无差异。这些数据表明IGF-I在这些患者中可能不发挥糖代谢的作用。2.成人生长激素缺乏症和肢端肥大症的血清脂肪细胞因子水平动脉粥样硬化和胰岛素抵抗是成人生长激素缺乏症和肢端肥大症的常见并发症。循环脂联素是一种脂肪细胞衍生的蛋白质，具有抗动脉粥样硬化和胰岛素增敏作用。肢端肥大症患者或成人GHD患者的胰岛素敏感性指标QUICKI值显着低于正常受试者（分别为0.33±0.03、0.35±0.04和0.36±0.01）。成人GHD患者的血清脂联素水平显着低于肢端肥大症患者（6.5±3.9,9.2±5.0，P<0.01），但与正常受试者的血清脂联素水平（7.8±4.3 μg/ml）没有显着差异。两组患者的血清脂联素水平与体重指数呈负相关。然而，仅在成人 GHD 患者中，血清脂联素水平与 QUICKI 呈正相关（Rs=0.37）。这些结果表明，成人 GHD 患者的脂联素水平显着低于肢端肥大症患者。 GHD 患者和健康对照者的脂联素水平相似，而在肢端肥大症患者中，与 BMI 相比，胰岛素抵抗似乎与脂联素水平并不密切相关。在成人 GHD 和肢端肥大症组中观察到的脂联素和 QUICKI 之间的不同关系可能反映了 GH 缺乏或过量状态下胰岛素抵抗机制的差异。还研究了 GHD 和肢端肥大症患者的血清抵抗素水平。较少的