Study for pathophysiological significance of growth hormone in adult men.

在本研究中，我们从以下几个方面探讨了生长激素在成年男性中的病理生理意义。成人生长激素缺乏症和肢端肥大症患者的代谢紊乱。回顾性分析东京女子医科大学成人GHD（AGHD）和肢端肥大症患者的临床和生化资料。在AGHD患者中，分别有4%和16%的患者存在糖尿病和糖耐量受损。42%的患者患有高胆固醇血症，41%患有高甘油三酯血症，55%的患者高密度脂蛋白胆固醇水平下降。35%的患者体重指数（BMI）为25 kg/m^2。异常表现包括内膜-中膜厚度（IMT）或斑块增加，分别见于27%和20%的患者。稳态模型胰岛素抵抗指数（HOMA-R）为2.87±0.38，提示胰岛素抵抗。这些数据提示脂糖代谢异常和动脉粥样硬化病变在成人GHD患者中更为常见。胰岛素抵抗可能在与GHD相关的糖脂代谢紊乱中起作用。肢端肥大症患者中，分别有45%和33%的患者存在糖尿病和糖耐量异常。肢端肥大症患者HOMA-R较高（3.59±0.56）。DM患者血清GH水平高于NGT患者，但各组间igf - 1水平和SDS水平无显著差异。这些数据提示igf - 1可能在这些患者中不起糖代谢的作用。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的作用。肢端肥大症和成人GHD患者的胰岛素敏感性指标QUICKI值明显低于正常人（分别为0.33±0.03、0.35±0.04和0.36±0.01）。成人GHD患者血清脂联素水平显著低于肢端肥大症患者（6.5±3.9,9.2±5.0，P<0.01），与正常人（7.8±4.3 μg/ml）差异无统计学意义。两组患者血清脂联素水平与BMI呈负相关。然而，血清脂联素水平仅在成人GHD患者中与QUICKI呈正相关（Rs=0.37,）。这些结果表明，成人GHD患者的脂联素水平明显低于肢端肥大症患者。脂联素水平在GHD患者和健康对照组中相似，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没有密切关系。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生长激素缺乏或过量状态下胰岛素抵抗机制的差异。同时还研究了GHD和肢端肥大症患者的血清抵抗素水平。少

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