Ronchi Cristina L, Varca Virginia, Beck-Peccoz Paolo, Orsi Emanuela, Donadio Francesca, Baccarelli Andrea, Giavoli Claudia, Ferrante Emanuele, Lania Andrea, Spada Anna, Arosio Maura
Institute of Endocrine Sciences, Fondazione Instituto di Ricovero e Cura a Carattere Scientifico, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20122 Milan, Italy.
J Clin Endocrinol Metab. 2006 Jan;91(1):121-8. doi: 10.1210/jc.2005-1704. Epub 2005 Nov 1.
The effects of chronic therapy with long-acting somatostatin analogs (SSTa) on metabolic and cardiovascular parameters have been partially elucidated in acromegalic patients.
The objective of this study was to compare the long-term effects of SSTa treatment and successful surgery on GH/IGF-I secretion and cardiovascular risk parameters in acromegaly. DESIGN, PATIENTS, AND INTERVENTION: This was a retrospective study of 36 acromegalic patients treated with SSTa and evaluated after a median of 66 months and of 33 sex-, age-, and body mass index-matched cured patients evaluated after a similar period of remission, all from the Institute of Endocrine Sciences (Milan, Italy).
The main outcome measures were fasting and post-oral load glucose homeostasis, hemoglobin A(1c), insulin sensitivity and secretion by several indexes, lipid profile, and blood pressure.
Fasting and areas under the glucose response curve rose in patients controlled (n = 29) and not controlled (n = 7) by SSTa, becoming higher than those in cured subjects. A 1% hemoglobin A(1c) increase was observed in all nondiabetic SSTa patients, but not in cured subjects. Basal insulin secretion and resistance, evaluated by homeostasis model assessment, decreased in all SSTa patients, whereas oral glucose tolerance test-derived insulin secretion and resistance, evaluated by insulinogenic index and oral glucose tolerance test-derived insulin secretion, improved only in SSTa-treated controlled patients. Triglycerides did not change during SSTa, whereas high-density lipoprotein cholesterol increased in SSTa-treated controlled patients. At the last visit, the contemporary presence of at least three cardiovascular risk factors was more frequent in patients treated with SSTa than in cured subjects.
SSTa therapy induces long-lasting disease control and improvement of insulin sensitivity and high-density lipoprotein cholesterol levels in responsive patients. The progressive glucose homeostasis alterations, observed independently from the degree of cure, suggest the need for glucose homeostasis and peripheral vascular complications monitoring during chronic SSTa treatment.
长效生长抑素类似物(SSTa)长期治疗对肢端肥大症患者代谢和心血管参数的影响已得到部分阐明。
本研究的目的是比较SSTa治疗与成功手术对肢端肥大症患者生长激素/胰岛素样生长因子-I(GH/IGF-I)分泌及心血管风险参数的长期影响。设计、患者与干预措施:这是一项回顾性研究,研究对象为36例接受SSTa治疗的肢端肥大症患者,中位随访66个月后进行评估,以及33例性别、年龄和体重指数匹配的已治愈患者,在相似的缓解期后进行评估,所有患者均来自意大利米兰内分泌科学研究所。
主要观察指标为空腹及口服葡萄糖负荷后的血糖稳态、糖化血红蛋白A1c、胰岛素敏感性及通过多种指标评估的胰岛素分泌、血脂谱和血压。
在接受SSTa治疗病情得到控制(n = 29)和未得到控制(n = 7)的患者中空腹血糖及葡萄糖反应曲线下面积均升高,且高于已治愈患者。所有非糖尿病SSTa治疗患者糖化血红蛋白A1c升高1%,而治愈患者未出现升高。通过稳态模型评估的基础胰岛素分泌及抵抗在所有SSTa治疗患者中均降低,而通过胰岛素生成指数及口服葡萄糖耐量试验衍生的胰岛素分泌评估的口服葡萄糖耐量试验衍生的胰岛素分泌及抵抗仅在接受SSTa治疗且病情得到控制的患者中得到改善。SSTa治疗期间甘油三酯未发生变化,而接受SSTa治疗且病情得到控制的患者高密度脂蛋白胆固醇升高。在最后一次随访时,接受SSTa治疗的患者中同时存在至少三种心血管危险因素的情况比已治愈患者更为常见。
SSTa治疗可使反应性患者实现持久的疾病控制,并改善胰岛素敏感性和高密度脂蛋白胆固醇水平。无论治愈程度如何均观察到血糖稳态的逐渐改变,提示在慢性SSTa治疗期间需要监测血糖稳态和外周血管并发症。