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阻塞性睡眠呼吸暂停在睡眠期间动态增加夜间血浆游离脂肪酸、葡萄糖和皮质醇水平。

Obstructive Sleep Apnea Dynamically Increases Nocturnal Plasma Free Fatty Acids, Glucose, and Cortisol During Sleep.

作者信息

Chopra Swati, Rathore Aman, Younas Haris, Pham Luu V, Gu Chenjuan, Beselman Aleksandra, Kim Il-Young, Wolfe Robert R, Perin Jamie, Polotsky Vsevolod Y, Jun Jonathan C

机构信息

Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21224.

Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

J Clin Endocrinol Metab. 2017 Sep 1;102(9):3172-3181. doi: 10.1210/jc.2017-00619.

Abstract

CONTEXT

Obstructive sleep apnea (OSA) is associated with diabetes and cardiovascular disease. This association may be related to metabolic changes that transpire during sleep in OSA.

OBJECTIVE

To examine the impact of OSA, elicited by cessation of continuous positive airway pressure (CPAP), on frequently sampled nocturnal metabolic markers including plasma free fatty acids (FFAs), glucose, insulin, triglycerides (TGs), cortisol, and lactate, as well as glucose production, oral glucose tolerance, blood pressure (BP), endothelial function, cholesterol, and high-sensitivity C-reactive protein (hsCRP).

DESIGN AND SETTING

Randomized crossover trial of CPAP vs CPAP withdrawal.

PATIENTS

Thirty-one patients with moderate to severe OSA acclimated to CPAP.

INTERVENTION

Patients underwent attended polysomnography while sleeping with therapeutic CPAP, or after CPAP withdrawal, in random order. Venous blood was sampled at ∼20-minute intervals on both nights. In 11 patients, we assessed glucose kinetics with an infusion of 6,6-[2H2]glucose.

RESULTS

CPAP withdrawal caused recurrence of OSA associated with hypoxemia, sleep disruption, and heart rate (HR) elevation. CPAP withdrawal dynamically increased nocturnal FFA (P = 0.007), glucose (P = 0.028), and cortisol (P = 0.037), in proportion to respiratory event frequency, HR elevation, or sleep fragmentation. Diabetes predisposed to glucose elevation. CPAP withdrawal also increased systolic BP (P = 0.017) and augmentation index (P = 0.008), but did not affect insulin, TGs, glucose production, oral glucose tolerance, cholesterol, or hsCRP.

CONCLUSION

OSA recurrence during CPAP withdrawal increases FFA and glucose during sleep, associated with sympathetic and adrenocortical activation. Recurring exposure to these metabolic changes may foster diabetes and cardiovascular disease.

摘要

背景

阻塞性睡眠呼吸暂停(OSA)与糖尿病和心血管疾病相关。这种关联可能与OSA睡眠期间发生的代谢变化有关。

目的

研究持续气道正压通气(CPAP)停止引发的OSA对频繁采样的夜间代谢标志物的影响,这些标志物包括血浆游离脂肪酸(FFA)、葡萄糖、胰岛素、甘油三酯(TG)、皮质醇和乳酸,以及葡萄糖生成、口服葡萄糖耐量、血压(BP)、内皮功能、胆固醇和高敏C反应蛋白(hsCRP)。

设计与地点

CPAP与停用CPAP的随机交叉试验。

患者

31例中度至重度OSA且已适应CPAP的患者。

干预措施

患者在使用治疗性CPAP睡眠时或停用CPAP后,按随机顺序接受有医护人员在场的多导睡眠监测。两晚均每隔约20分钟采集静脉血样。在11例患者中,我们通过输注6,6-[2H2]葡萄糖评估葡萄糖动力学。

结果

停用CPAP导致OSA复发,伴有低氧血症、睡眠中断和心率(HR)升高。停用CPAP使夜间FFA(P = 0.007)、葡萄糖(P = 0.028)和皮质醇(P = 0.037)动态增加,与呼吸事件频率、HR升高或睡眠碎片化程度成比例。糖尿病患者更易出现葡萄糖升高。停用CPAP还使收缩压(P = 0.017)和增强指数(P = 0.008)升高,但对胰岛素、TG、葡萄糖生成、口服葡萄糖耐量、胆固醇或hsCRP无影响。

结论

停用CPAP期间OSA复发会使睡眠期间FFA和葡萄糖增加,与交感神经和肾上腺皮质激活有关。反复暴露于这些代谢变化可能会促进糖尿病和心血管疾病的发生。

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