Henley David E, Buchanan Fiona, Gibson Rosemary, Douthwaite Jennie A, Wood Susan A, Woltersdorf Wolfram W, Catterall James R, Lightman Stafford L
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, UK.
J Endocrinol. 2009 Oct;203(1):181-8. doi: 10.1677/JOE-09-0245. Epub 2009 Jul 30.
Apelin is a peptide hormone with cardiovascular and glucose homeostasis properties, and obstructive sleep apnea (OSA) is complicated by cardiovascular and metabolic comorbidities. Plasma apelin has not been previously assessed in OSA. We investigated the response of plasma apelin to a 2-h 75 g oral glucose tolerance test (OGTT) and the effect of 3 months compliant continuous positive airway pressure (CPAP) therapy in 15 obese males with newly diagnosed OSA. Plasma apelin and serum cortisol were recorded 10 minutely, while serum insulin and glucose were measured 30 minutely. Ten subjects had plasma apelin measured at intervals across a 24-h period to investigate for circadian variation in apelin levels, and this was repeated following 3 months compliant CPAP therapy. Fasting (0.342+/-0.038 vs 0.288+/-0.024 ng/ml, P=0.04), 30 min (0.399+/-0.035 vs 0.312+/-0.036 ng/ml, P=0.007) and 120 min (0.402+/-0.030 vs 0.259+/-0.024 ng/ml, P<0.001) apelin levels were reduced following CPAP. The area under curve for apelin OGTT response was lower post-CPAP (44.1+/-3.3 vs 35.8+/-2.3 ng/ml per min, P<0.001). Mean OGTT apelin levels showed a significant treatment effect (P=0.006) and a time effect (P<0.001), and the effect of time was different pre- versus post-CPAP (P=0.005). No significant variability in apelin levels existed across the 24-h period at diagnosis. Lower levels were evident overnight following treatment (P=0.004). Improvements in insulin and glucose parameters and reduced cortisol levels were found post-CPAP. In summary, untreated OSA was associated with elevated plasma apelin levels, altered apelin secretory dynamics in response to oral glucose and lack of an apparent circadian variability, which was restored following CPAP.
阿片肽是一种具有心血管和葡萄糖稳态特性的肽类激素,而阻塞性睡眠呼吸暂停(OSA)常伴有心血管和代谢合并症。此前尚未对OSA患者的血浆阿片肽进行评估。我们调查了15名新诊断为OSA的肥胖男性在进行2小时75克口服葡萄糖耐量试验(OGTT)时血浆阿片肽的反应,以及3个月持续气道正压通气(CPAP)治疗的效果。每隔10分钟记录血浆阿片肽和血清皮质醇水平,同时每隔30分钟测量血清胰岛素和葡萄糖水平。10名受试者在24小时内每隔一段时间测量血浆阿片肽水平,以研究阿片肽水平的昼夜变化,并在3个月的CPAP依从性治疗后重复测量。CPAP治疗后,空腹(0.342±0.038对0.288±0.024 ng/ml,P = 0.04)、30分钟(0.399±0.035对0.312±0.036 ng/ml,P = 0.007)和120分钟(0.402±0.030对0.259±0.024 ng/ml,P<0.001)时的阿片肽水平降低。CPAP治疗后,阿片肽OGTT反应的曲线下面积较低(44.1±3.3对35.8±2.3 ng/ml每分钟,P<0.001)。平均OGTT阿片肽水平显示出显著的治疗效果(P = 0.006)和时间效应(P<0.001),且CPAP治疗前后的时间效应不同(P = 0.005)。诊断时,24小时内阿片肽水平无显著变化。治疗后夜间水平明显降低(P = 0.004)。CPAP治疗后胰岛素和葡萄糖参数有所改善,皮质醇水平降低。总之,未经治疗的OSA与血浆阿片肽水平升高、口服葡萄糖后阿片肽分泌动力学改变以及缺乏明显的昼夜变化有关,而CPAP治疗后这些情况得以恢复。