葡萄糖代谢、昼夜节律与低氧之间的关联：阻塞性睡眠呼吸暂停患者 NPAS2 和 Rev-Erb-α 蛋白血清水平评估——一项初步研究。

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.

机构信息

Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, Poland.

Department of Gynecology, Oncological Gynecology and Treatment of Endometriosis, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland.

出版信息

Dent Med Probl. 2024 May-Jun;61(3):465-469. doi: 10.17219/dmp/185718.

DOI:10.17219/dmp/185718

PMID:38804230

Abstract

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 (SpO2) 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.

摘要

背景

阻塞性睡眠呼吸暂停（OSA）是 2 型糖尿病（DM2）的危险因素之一。由于 OSA 与昼夜节律紊乱有关，它会影响昼夜节律蛋白，包括神经元 PAS 结构域蛋白 2（NPAS2）和核受体亚家族 1 组 D 成员 1（Rev-Erb-α）。这些蛋白已被证明与代谢异常有关，如胰岛素抵抗。

目的

本初步研究旨在比较严重 OSA 组和严重 OSA+DM2 组与健康对照组患者的 NPAS2 和 Rev-Erb-α 蛋白血清水平，并考虑与多导睡眠图（PSG）参数的相关性（例如，氧饱和度（SpO2）变量）。

材料和方法

共有 40 名参与者被纳入研究。他们被分为 3 组：OSA 组（n = 17；呼吸暂停低通气指数（AHI）>30，无 DM2）；OSA+DM2 组（n = 7；AHI > 30 且 DM2）；对照组（n = 16；AHI < 5，无 DM2）。所有参与者都进行了夜间 PSG 检查，并在第二天早上采集血液。使用酶联免疫吸附试验（ELISA）评估 NPAS2 和 Rev-Erb-α 蛋白的血清水平。

结果

与健康个体相比，OSA 组的 NPAS2 蛋白水平显著降低（p = 0.017）。此外，与 OSA+DM2 组相比，OSA 组的 NPAS2 蛋白水平也较低，但仅呈现出趋势（p = 0.094）。Rev-Erb-α 蛋白浓度无差异。此外，还观察到快速眼动（REM）睡眠期间 AHI 与 NPAS2 蛋白血清水平呈负相关（r = -0.478；p = 0.002）。