Plöckinger U, Reuter T
Interdisziplinäres Stoffwechsel-Centrum: Endokrinologie, Diabetes und Stoffwechsel, Med. Klinik m S Hepatologie und Gastroenterologie, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Eur J Endocrinol. 2008 Apr;158(4):467-71. doi: 10.1530/EJE-07-0637.
Acromegalic patients have increased lipolysis and decreased fat mass as well as reduced insulin sensitivity and glucose intolerance. During somatostatin analog therapy, these changes persist despite GH suppression, but they are now due to drug-induced suppression of insulin secretion. By contrast, during pegvisomant (PEG) therapy, GH no longer stimulates lipolysis due to the blockade of its receptor, while insulin action is unabated. Hence, both insulin sensitivity and fat mass, including intra-abdominal fat, should increase. We therefore studied intra-abdominal fat and insulin resistance in acromegalic patients after a 3-month octreotide-washout period, i.e., during untreated acromegaly, and during PEG treatment.
Five acromegalic patients, not controlled on octreotide (OCT) therapy, were studied after 3-month OCT washout and 6-month PEG therapy. Insulin sensitivity was determined by homeostatic model assessment value and hyperinsulinemic, normoglycemic clamp. Subcutaneous and intra-abdominal fat were measured by electron beam computed tomography.
During PEG therapy, all the patients had normal, age-adjusted IGF-I concentrations. Compared with washout, insulin sensitivity (HOMA and M value) was not significantly different. However, intra-abdominal fat mass increased significantly during therapy (median (range) cm(2): 112 (84-480) and 172 (112-524) respectively, P<0.05), while subcutaneous fat was not significantly different. Low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides remained unchanged.
During PEG therapy of acromegalic patients, intra-abdominal fat increases. Visceral obesity is a risk factor for cardiovascular disease. Hence, confirmation and further studies in a larger cohort of acromegalic patients on PEG treatment are warranted.
肢端肥大症患者脂解作用增强、脂肪量减少，同时胰岛素敏感性降低且存在葡萄糖不耐受。在生长抑素类似物治疗期间，尽管生长激素受到抑制，但这些变化仍然存在，不过此时是药物诱导的胰岛素分泌受抑制所致。相比之下，在培维索孟（PEG）治疗期间，由于生长激素受体被阻断，生长激素不再刺激脂解作用，而胰岛素作用未减弱。因此，胰岛素敏感性和脂肪量，包括腹部脂肪，均应增加。我们因此研究了肢端肥大症患者在经过3个月的奥曲肽洗脱期（即未治疗的肢端肥大症期间）以及PEG治疗期间的腹部脂肪和胰岛素抵抗情况。
对5例奥曲肽（OCT）治疗效果不佳的肢端肥大症患者在经过3个月的OCT洗脱期和6个月的PEG治疗后进行研究。通过稳态模型评估值和高胰岛素正常血糖钳夹试验来测定胰岛素敏感性。采用电子束计算机断层扫描测量皮下和腹部脂肪。
在PEG治疗期间，所有患者的年龄调整后的胰岛素样生长因子-I（IGF-I）浓度均正常。与洗脱期相比，胰岛素敏感性（稳态模型评估值和M值）无显著差异。然而，治疗期间腹部脂肪量显著增加（中位数（范围）cm²：分别为112（84 - 480）和172（112 - 524），P<0.05），而皮下脂肪无显著差异。低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和甘油三酯保持不变。
在肢端肥大症患者的PEG治疗期间，腹部脂肪增加。内脏肥胖是心血管疾病的危险因素。因此，有必要在更大规模的接受PEG治疗的肢端肥大症患者队列中进行证实和进一步研究。
