How is Obstructive Sleep Apnea Associated with High Blood Pressure and Diabetes Mellitus Type 2? Clues from a Two-Step Mendelian Randomized Study

Yubin Shen; Hongwei Wang; Weiyu Zhang; Xiwen Ou; Song Liu

doi:10.2147/NSS.S423331

How is Obstructive Sleep Apnea Associated with High Blood Pressure and Diabetes Mellitus Type 2? Clues from a Two-Step Mendelian Randomized Study

Nat Sci Sleep. 2023 Sep 29:15:749-765. doi: 10.2147/NSS.S423331. eCollection 2023.

Authors

Yubin Shen^#¹, Hongwei Wang^#¹, Weiyu Zhang¹, Xiwen Ou¹, Song Liu¹

Affiliation

¹ Department of Respiratory Medicine and Sleep Lab, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People's Republic of China.

^# Contributed equally.

Abstract

Background: Obstructive sleep apnea (OSA), high blood pressure (HBP), and type 2 diabetes mellitus (T2DM) have a close clinical relationship, but whether and how OSA affects HBP and T2DM is unclear.

Study design and methods: Two-step, two-sample Mendelian randomization techniques were applied using single-nucleotide polymorphisms as genetic instruments for exposure and mediators, thus minimizing bias due to confounding factors and reverse causality. The total effect of OSA on HBP and T2DM was categorized into direct and mediating effects based on the mediating factors.

Results: Two-sample MR analysis showed that OSA increased the risk of HBP (odds ratio [OR] = 1.010, 95% confidence interval [CI], 1.002-1.018; P = 0.0121) and T2DM (OR = 1.140, 95% CI, 1.059-1.228; P = 0.0005). In the process of OSA caused by HBP, sex hormone-binding globulin (SHBG) (female, 4.47% mediation; male, 2.76% mediation), total testosterone (TT) (male, 3.72% mediation), bioavailable testosterone (BioT) (female, 7.74% mediation), high-density lipoprotein cholesterol (HDL-C) (3.25% mediation), and apolipoprotein A1 (ApoA1) (1.31% mediation) were individual contributors. SHBG (female, 4.10% mediation; male, 1.58% mediation), TT (male, 3.69% mediation), BioT (female, 2.58% mediation), HDL-C (3.32% mediation), ApoA1 (2.14% mediation), and omega-6 fatty acids (2.33% mediation) may have mediating roles to varying degrees in the process of OSA caused by T2DM.

Interpretation: This MR study showed that OSA is a risk factor for HBP and T2DM, and the evaluation of mediators may help further reveal the specific mechanism by which OSA causes HBP and T2DM.

Keywords: Mendelian randomization; high blood pressure; mediating factors; obstructive sleep apnea; type 2 diabetes mellitus.

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number 81873423]. The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.