Association between glucose metabolism, the circadian cycle and hypoxia: Evaluation of the NPAS2 and Rev-Erb-α protein serum levels in obstructive sleep apnea patients – a pilot study

Background.Obstructive sleep apnea (OSA) is one of the risk factors for diabetes mellitus type 2 (DM2).As OSA is associated with the disruption of the circadian rhythm, it affects circadian clock proteins, including neuronal PAS domain protein 2 (NPAS2) and nuclear receptor subfamily 1 group D member 1 (Rev-Erb-α).These proteins have been shown to be related to metabolic abnormalities, i.a., insulin resistance.Objectives.The present pilot study aimed to investigate the NPAS2 and Rev-Erb-α protein serum levels in the groups of patients with severe OSA and severe OSA+DM2 in comparison with healthy controls, taking into account correlations with polysomnography (PSG) parameters (e.g., oxygen saturation (SpO 2 ) variables). Material and methods.A total of 40 participants were included in the study.They were split into 3 groups as follows: the OSA group (n = 17; apnea-hypopnea index (AHI) >30, no DM2); the OSA+DM2 group (n = 7; AHI > 30 and DM2); and the control group (n = 16; AHI < 5, no DM2).All participants underwent a nocturnal PSG examination and had their blood collected the following morning.The serum levels of NPAS2 and Rev-Erb-α proteins were assessed using the enzyme-linked immunosorbent assay (ELISA). Results.The mean NPAS2 protein level was significantly lower in the OSA group as compared to healthy individuals (p = 0.017).Additionally, the OSA group presented with lower NPAS2 protein levels as compared to the OSA+DM2 group, but only a tendency was observed (p = 0.094).No differences in the Rev-Erb-α protein concentration were noticed.Furthermore, a negative correlation between AHI during rapid eye movement (REM) sleep and the NPAS2 protein serum level was observed (r = -0.478;p = 0.002).Conclusions.Serum NPAS2 protein might be involved in metabolic dysregulation present among OSA patients, while the mechanism itself may be associated with REM sleep.