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

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.

Trial registration: ClinicalTrials.gov NCT02824263.

Copyright © 2017 Endocrine Society

Figures

Figure 1.

Effect of CPAP withdrawal on sleep physiology. Data are plotted as mean ± standard error of the mean (n = 31) at 20-minute intervals. OSA data are shown in blue; CPAP data are shown in red. The shaded region, from 11 pm to 7 am, denotes the sleep/lights out period. Respiratory events = (apneas + hypopneas) in preceding 20 minutes. β coefficients and P values reflect differences between OSA and CPAP using mixed effects models. BPM, beats per minute.

Figure 2.

Effect of CPAP withdrawal on nocturnal metabolic profiles. OSA data are in blue; CPAP data are in red. Values are plotted as mean ± standard error of the mean (n = 31). The shaded region from 11 pm to 7 am denotes the sleep/lights out period. β coefficients and P values reflect differences between OSA and CPAP using mixed effects models, and do not include the OGTT period.

Figure 3.

Effect of CPAP withdrawal on glucose kinetics in patients receiving 6,6-[2H2] glucose. (a) Plasma glucose, insulin, rate of glucose appearance (Ra), disappearance (Rd), or MCR were unchanged (n = 11). (b) In patients who exhibited OSA-induced hyperglycemia (n = 4), there was no increase in glucose production but a fall in MCR and an early and persistent rise in insulin, suggesting peripheral insulin resistance.