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

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


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Blood Glucose / analysis*
  • Cardiovascular Diseases / prevention & control
  • Circadian Rhythm*
  • Continuous Positive Airway Pressure / methods
  • Cross-Over Studies
  • Fatty Acids, Nonesterified / blood*
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / blood*
  • Male
  • Middle Aged
  • Oxygen Consumption / physiology
  • Polysomnography
  • Predictive Value of Tests
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Sleep / physiology
  • Sleep Apnea, Obstructive / blood*
  • Sleep Apnea, Obstructive / diagnosis
  • Sleep Apnea, Obstructive / therapy*
  • Treatment Outcome
  • Withholding Treatment


  • Biomarkers
  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Hydrocortisone

Associated data

  • ClinicalTrials.gov/NCT02824263