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肢端肥大症中的葡萄糖稳态:长效生长抑素类似物治疗的效果

Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment.

作者信息

Baldelli Roberto, Battista Claudia, Leonetti Frida, Ghiggi Maria-Rosaria, Ribaudo Maria-Cristina, Paoloni Antonella, D'Amico Eugenio, Ferretti Elisabetta, Baratta Roberto, Liuzzi Antonio, Trischitta Vincenzo, Tamburrano Guido

机构信息

Department of Clinical Sciences, Endocrinology Section, University of Rome, Rome, Italy.

出版信息

Clin Endocrinol (Oxf). 2003 Oct;59(4):492-9. doi: 10.1046/j.1365-2265.2003.01876.x.

Abstract

OBJECTIVE

Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty-four active acromegalic patients were studied in order to determine the long-term effects of octreotide-LAR and SR-lanreotide on insulin sensitivity and carbohydrate metabolism.

DESIGN

Prospective study.

PATIENTS

We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50.7 +/- 12.7 years, body mass index (BMI) 30.1 +/- 4.8 (kg/m2).

MEASUREMENTS

All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy.

RESULTS

Acromegalic patients showed low M-values in respect to the control group at baseline (P<0.05), followed by a significant improvement after 6 months of therapy (P<0.005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P<0.05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P<0.05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4.7 +/- 0.6% and 5.1 +/- 0.5%, basal and after six months, respectively, P<0.005).

CONCLUSION

In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy.

摘要

目的

肢端肥大症是一种糖耐量受损(IGT)和糖尿病(DM)风险较高的综合征。用于肢端肥大症医学治疗的生长抑素类似物可能对葡萄糖稳态产生不同的激素影响。对24例活动期肢端肥大症患者进行研究,以确定奥曲肽长效释放制剂和缓释兰瑞肽对胰岛素敏感性和碳水化合物代谢的长期影响。

设计

前瞻性研究。

患者

我们研究了24例活动期肢端肥大症患者,其中男性11例,女性13例,年龄50.7±12.7岁,体重指数(BMI)为30.1±4.8(kg/m2)。

测量

所有患者均接受口服葡萄糖耐量试验(OGTT),12例患者还进行了正常血糖高胰岛素钳夹试验。所有患者在基线时和生长抑素类似物治疗6个月后进行评估。

结果

肢端肥大症患者在基线时相对于对照组的M值较低(P<0.05),治疗6个月后有显著改善(与基线相比P<0.005)。糖耐量正常的患者在生长抑素类似物治疗期间,OGTT 120分钟时的血清葡萄糖水平恶化(P<0.05),但糖耐量受损或糖尿病患者则不然。这与OGTT期间胰岛素分泌减少(P<0.05)和延迟30分钟有关。此外,所有受试者治疗后的糖化血红蛋白(HbA1c)均显著恶化(基线时为4.7±0.6%,6个月后为5.1±0.5%,P<0.005)。

结论

在肢端肥大症患者中,生长抑素类似物治疗可降低胰岛素抵抗,但也会损害胰岛素分泌。这可能表明,对于在生长抑素类似物治疗期间出现明显高血糖的肢端肥大症患者,应考虑使用口服促分泌降糖药和/或胰岛素治疗,而不是胰岛素增敏剂作为首选治疗方法。

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