Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, University of São Paulo Medical School, Av. Dr. Eneas de Carvalho, 255, 7ºandar, sala 7037, Instituto Central, Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil.
Pituitary. 2013 Sep;16(3):341-50. doi: 10.1007/s11102-012-0430-8.
Sleep Apnea is highly prevalent and may contribute to insulin resistance in patients with acromegaly. The primary aim of this study was to assess the impact of sleep apnea treatment with a continuous positive air pressure (CPAP) device on insulin resistance evaluated by hyperinsulinemic euglycemic clamp (HEC). A prospective, randomized, open label, placebo-controlled, crossover study was performed at a tertiary outpatient pituitary center. Twelve acromegalic subjects on somatostatin analogs (SA) with a recent diagnosis of moderate to severe sleep apnea were randomized to CPAP therapy or to nasal dilator adhesive (NDA) with placebo effect for 3 months and then crossed over for another 3 months period without washout. Assessment of HEC, mathematical insulin resistance indexes (HOMA, HOMA2 and QUICKI), GH, IGF-1, HbA1c and free fat acids were performed. A significant reduction on insulin resistance was demonstrated by HEC at the end of the study in patients on CPAP (HEC, pre- and post-CPAP: 4.27 vs. 6.10 mg/Kg/min, P = 0.032). This reduction was not observed in NDA group (HEC, pre- and post-adhesive: 5.53 vs. 5.19 mg/Kg/min, P = 0.455). There was no significant difference on HbA1c or on peripheral insulin resistance indexes in both treatments. CPAP promoted a significant increase on peripheral insulin sensitivity in acromegalic patients with moderate to severe sleep apnea on SA use. Our results support the concept that sleep apnea plays an important role on glucose metabolism. Insulin resistance indexes were unable to detect this finding.
睡眠呼吸暂停在肢端肥大症患者中非常普遍，可能导致胰岛素抵抗。本研究的主要目的是评估使用持续气道正压通气（CPAP）设备治疗睡眠呼吸暂停对高胰岛素-正葡萄糖钳夹（HEC）评估的胰岛素抵抗的影响。这是在一家三级门诊垂体中心进行的前瞻性、随机、开放标签、安慰剂对照、交叉研究。12 名接受生长抑素类似物（SA）治疗且近期诊断为中重度睡眠呼吸暂停的肢端肥大症患者被随机分为 CPAP 治疗组或鼻腔扩张器黏贴剂（NDA）安慰剂组，每组治疗 3 个月，然后交叉治疗 3 个月，期间不进行洗脱。评估 HEC、数学胰岛素抵抗指数（HOMA、HOMA2 和 QUICKI）、GH、IGF-1、HbA1c 和游离脂肪酸。CPAP 治疗组患者在研究结束时 HEC 显示胰岛素抵抗显著降低（HEC，治疗前和治疗后：4.27 比 6.10mg/Kg/min，P = 0.032）。在 NDA 组未观察到这种降低（HEC，治疗前和治疗后：5.53 比 5.19mg/Kg/min，P = 0.455）。两种治疗方法均未HbA1c 或外周胰岛素抵抗指数有显著差异。CPAP 可显著提高使用 SA 的中重度睡眠呼吸暂停肢端肥大症患者的外周胰岛素敏感性。我们的研究结果支持睡眠呼吸暂停对葡萄糖代谢有重要影响的概念。胰岛素抵抗指数无法检测到这一发现。
