Obstructive sleep apnea (OSA) is related to obesity and metabolic disorders. The main clinical symptoms are excessive daytime sleepiness (EDS) and snoring. However, not all patients with OSA manifest EDS. Hypocretin-1, neuropeptide Y, leptin, ghrelin and adiponectin are implicated in both metabolic and sleep regulation, two conditions affected by OSA. We hypothesized that levels of these peptides may be related to EDS in OSA patients.

We included 132 patients with EDS, as defined by an Epworth Sleepiness Scale (ESS) score ≥13 (mean ± SD, 15.7 ± 2.3) and 132 patients without EDS as defined by an ESS score ≤9 (6.5 ± 1.9). All patients had an apnea–hypopnea index (AHI) ≥ 20 h⁻¹. Both groups were matched for gender (males; 83.3% vs. 85.6%), age (50.15 ± 11.2 yrs vs. 50.7 ± 9.9 yrs), body mass index (BMI) (31.8 ± 5.6 kg m⁻² vs. 32.1 ± 4.8 kg m⁻²), and apnea–hypopnea index (AHI) (45.5 ± 19.1 h⁻¹ vs. 43 ± 19.2 h⁻¹).

OSA patients with EDS showed significantly higher plasma hypocretin-1 levels (p < 0.001) and lower plasma ghrelin levels (p < 0.001) than OSA patients without EDS. There were no statistically significant differences in neuropeptide Y (p = 0.08), leptin (p = 0.07) and adiponectin (p = 0.72) between the two groups. In the multiple linear regression model ESS score was associated with plasma levels of hypocretin-1, ghrelin and total sleep time.

Our study shows that EDS in patients with OSA is associated with increased circulating hypocretin-1 and decreased circulating ghrelin levels, two peptides involved in the regulation of body weight, energy balance, sympathetic tone and sleep–wake cycle. This relationship is independent of AHI and obesity (two key phenotypic features of OSA).