背景:阻塞性睡眠呼吸暂停(OSA)通常与胰岛素抵抗(IR)和血脂异常有关。载脂蛋白E(APOE)在脂质代谢中起重要作用。该研究旨在基于OSA的大规模人群,理清IR和APOE之间的多因素关系。
方法:最终纳入了5,591名接受多导睡眠监测诊断OSA的参与者。我们采集了人体测量,每位参与者的空腹生化和多导睡眠图数据。进行线性回归分析以评估APOE,IR,和睡眠呼吸相关参数。Logistic回归,限制性三次样条(RCS)和中介分析用于探索OSA患者APOE与IR之间的关系.
结果:OSA严重程度增加与肥胖增加有关,更明显的血脂异常,和更高水平的APOE和IR。APOE与呼吸暂停低通气指数(AHI)呈正相关,氧饱和度下降指数(ODI)和微觉醒指数(MAI),即使调整了年龄,性别,身体质量指数,以及吸烟和饮酒水平(分别为β=0.107,β=0.102,β=0.075,所有P<0.001)。IR的风险从APOE的第一到第四四分位数增加(比值比(OR)=1.695,95%CI:1.425-2.017;OR=2.371,95%置信区间(CI):2.009-2.816;OR=3.392,95%CI:2.853-4.032,所有P<0.001)。RCS分析表明APOE之间存在非线性和剂量反应关系,AHI,ODI,MAI和胰岛素抵抗。中介分析表明,HOMA-IR解释了AHI之间9.1%和10%的关联,ODI和APOE。在男性中观察到相同的趋势,但不是女人。
结论:这项研究表明,APOE是IR的危险因素;此外,IR在男性中充当OSA和APOE之间的介体。APOE,IR,OSA呈非线性和多阶段关系。一起来看,这些观察揭示了OSA患者代谢紊乱的复杂关系,这可能导致新的治疗方式的发展和对OSA的系统性影响的更深入的理解。
BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The
study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA.
METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA.
RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (β = 0.107, β = 0.102, β = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women.
CONCLUSIONS: This
study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.