Drake W M, Rowles S V, Roberts M E, Fode F K, Besser G M, Monson J P, Trainer P J
Department of Endocrinology, St Bartholomew's Hospital, London, UK.
Eur J Endocrinol. 2003 Dec;149(6):521-7. doi: 10.1530/eje.0.1490521.
Insulin resistance leading, in some cases, to glucose intolerance is an important contributory factor to the cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to document changes in insulin sensitivity (IS) in a group of seven patients with acromegaly (three male, four female, mean+/-s.d. age 59+/-13 Years) treated initially with a stable dose of depot octreotide (OT; median dose 30 mg four times weekly, range 10-30 mg) for a median of 18 Months (range 16-19 Months) and who were then transferred to treatment with pegvisomant (median dose 15 mg daily, range 10-20 mg) for a median of 8 Months (range 7-9 Months). IS was assessed by homeostatic model assessment (HOMA) using fasting glucose and insulin concentrations and by a short insulin tolerance test (sITT). Body composition was assessed by dual energy X-ray absorptiometry.
Mean+/-s.d. serum IGF-I concentrations during therapy with OT and with pegvisomant were not statistically different (283+/-119 ng/ml on OT vs 191+/-39 ng/ml on pegvisomant (P=0.4)). However, mean+/-s.d. fasting plasma glucose fell from 6.2+/-1.0 mmol/l on OT to 5.2+/-0.6 mmol/l on pegvisomant (P=0.017) and was lower on pegvisomant in all seven patients. In four patients, fasting plasma glucose fell from values diagnostic of diabetes mellitus or impaired fasting glucose on OT to within the normal range on pegvisomant. Mean+/-s.d. peripheral IS (by sITT) increased from 139+/-39 micromol/l per min on OT to 169+/-59 micromol/l per min on pegvisomant (P=0.037). Mean+/-s.d. IS (by HOMA %S) was unchanged over the course of the study (149.1+/-43.7% on OT vs 139.9+/-76.6% on pegvisomant, P=0.28). Mean+/-s.d. pancreatic beta-cell secretory function (HOMA %B) improved significantly on pegvisomant compared with OT (49.4+/-19.2% vs 82.4+/-43.5%, P=0.01). No statistically significant change in total fat (P=0.3), % fat (P=0.28) or circulating non-esterified fatty acids (P=0.35) was observed.
IS and glucose tolerance improved in patients converted from OT therapy to pegvisomant, without a change in body composition and even when serum IGF-I concentrations remained equally well controlled. This may be an important factor in the choice of medical therapy for patients with acromegaly.
胰岛素抵抗在某些情况下会导致葡萄糖耐量异常，是肢端肥大症相关心血管疾病发病率和死亡率的一个重要促成因素。本研究的目的是记录一组7例肢端肥大症患者（3例男性，4例女性，平均±标准差年龄59±13岁）的胰岛素敏感性（IS）变化。这些患者最初接受稳定剂量的长效奥曲肽（OT；中位剂量30mg，每周4次，范围10 - 30mg）治疗，中位时间为18个月（范围16 - 19个月），随后转为培维索孟治疗（中位剂量15mg/天，范围10 - 20mg），中位时间为8个月（范围7 - 9个月）。通过使用空腹血糖和胰岛素浓度的稳态模型评估（HOMA）以及短胰岛素耐量试验（sITT）来评估IS。通过双能X线吸收法评估身体成分。
OT治疗和培维索孟治疗期间血清IGF - I浓度的平均±标准差无统计学差异（OT治疗时为283±119ng/ml，培维索孟治疗时为191±39ng/ml，P = 0.4）。然而，空腹血浆葡萄糖平均±标准差从OT治疗时的6.2±1.0mmol/l降至培维索孟治疗时的5.2±0.6mmol/l（P = 0.017），且7例患者中培维索孟治疗时的空腹血糖均较低。4例患者的空腹血糖从OT治疗时诊断为糖尿病或空腹血糖受损的值降至培维索孟治疗时的正常范围内。外周IS（通过sITT）平均±标准差从OT治疗时的139±39μmol/l每分钟增加至培维索孟治疗时的169±59μmol/l每分钟（P = 0.037）。在研究过程中，IS（通过HOMA %S）平均±标准差无变化（OT治疗时为149.1±43.7%，培维索孟治疗时为139.9±76.6%，P = 0.28）。与OT相比，培维索孟治疗时胰腺β细胞分泌功能（HOMA %B）显著改善（49.4±19.2%对82.4±43.5%，P = 0.01）。未观察到总脂肪（P = 0.3）、脂肪百分比（P = 0.28）或循环非酯化脂肪酸（P = 0.35）有统计学显著变化。
从OT治疗转为培维索孟治疗的患者，IS和葡萄糖耐量得到改善，身体成分无变化，即使血清IGF - I浓度保持同样良好的控制。这可能是肢端肥大症患者选择药物治疗的一个重要因素。
