Liu Qianqian, Chang Xingyu, Lian Rongna, Chen Qi, Wang Jialei, Fu Songbo
Department of Endocrinology, First Hospital of Lanzhou University, Lanzhou, Gansu, China.
Gansu Provincial Endocrine Disease Clinical Medicine Research Center, Lanzhou, Gansu, China.
Front Cardiovasc Med. 2024 May 9;11:1340602. doi: 10.3389/fcvm.2024.1340602. eCollection 2024.
The relationship between obstructive sleep apnea syndrome (OSAS) and diabetic microangiopathy remains controversial.
This study aimed to use bidirectional two-sample Mendelian Randomization (MR) to assess the causal relationship between OSAS and diabetic microangiopathy.
First, we used the Linkage Disequilibrium Score Regression(LDSC) analysis to assess the genetic correlation. Then, the bidirectional two-sample MR study was conducted in two stages: OSAS and lung function-related indicators (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) were investigated as exposures, with diabetic microangiopathy as the outcome in the first stage, and genetic tools were used as proxy variables for OSAS and lung function-related measures in the second step. Genome-wide association study data came from the open GWAS database. We used Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted median, Simple mode, and Weighted mode for effect estimation and pleiotropy testing. We also performed sensitivity analyses to test the robustness of the results. Furthermore, we performed multivariate and mediation MR analyses.
In the LDSC analysis, We found a genetic correlation between OSAS, FVC, FEV 1, and diabetic microangiopathy. In the MR analysis, based on IVW analysis, genetically predicted OSAS was positively correlated with the incidence of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). In the subgroup analysis of DR, there was a significant causal relationship between OSAS and background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). The reverse MR did not show a correlation between the incidence of diabetic microangiopathy and OSAS. Reduced FVC had a potential causal relationship with increased incidence of DR and PDR. Reduced FEV1 had a potential causal relationship with the increased incidence of BDR, PDR, and DKD. Multivariate MR analysis showed that the association between OSAS and diabetic microangiopathy remained significant after adjusting for confounding factors. However, we did not find the significant mediating factors.
Our results suggest that OSAS may be a cause of the development of diabetic microangiopathy, and OSAS may also be associated with a high risk of diabetic microangiopathy, providing a reference for a better understanding of the prevention of diabetic microangiopathy.
阻塞性睡眠呼吸暂停综合征（OSAS）与糖尿病微血管病变之间的关系仍存在争议。
本研究旨在采用双向双样本孟德尔随机化（MR）方法评估OSAS与糖尿病微血管病变之间的因果关系。
首先，我们采用连锁不平衡评分回归（LDSC）分析来评估遗传相关性。然后，双向双样本MR研究分两个阶段进行：第一阶段，将OSAS及肺功能相关指标（用力肺活量（FVC）和第1秒用力呼气量（FEV1））作为暴露因素，糖尿病微血管病变作为结局；第二步，使用遗传工具作为OSAS和肺功能相关指标的替代变量。全基因组关联研究数据来自开放的GWAS数据库。我们使用逆方差加权（IVW）、MR-Egger回归、加权中位数、简单模式和加权模式进行效应估计和多效性检验。我们还进行了敏感性分析以检验结果的稳健性。此外，我们进行了多变量和中介MR分析。
在LDSC分析中，我们发现OSAS、FVC、FEV1与糖尿病微血管病变之间存在遗传相关性。在MR分析中，基于IVW分析，遗传预测的OSAS与糖尿病视网膜病变（DR）、糖尿病肾病（DKD）和糖尿病神经病变（DN）的发生率呈正相关。在DR的亚组分析中，OSAS与背景性糖尿病视网膜病变（BDR）和增殖性糖尿病视网膜病变（PDR）之间存在显著的因果关系。反向MR未显示糖尿病微血管病变的发生率与OSAS之间存在相关性。FVC降低与DR和PDR发生率增加之间存在潜在因果关系。FEV1降低与BDR、PDR和DKD发生率增加之间存在潜在因果关系。多变量MR分析表明，在调整混杂因素后，OSAS与糖尿病微血管病变之间的关联仍然显著。然而，我们未发现显著的中介因素。
我们的结果表明，OSAS可能是糖尿病微血管病变发生的一个原因，并且OSAS也可能与糖尿病微血管病变的高风险相关，为更好地理解糖尿病微血管病变的预防提供了参考。
