糖尿病与主动脉夹层：通过孟德尔随机化研究 3-羟基丁酸的作用。

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

机构信息

Department of Cardiac Surgery, The Second Hospital of Shandong University, 250033, Jinan, Shandong, China.

Department of Cadre Health Care, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shangdong, People's Republic of China.

出版信息

Cardiovasc Diabetol. 2024 May 7;23(1):159. doi: 10.1186/s12933-024-02266-3.

DOI:10.1186/s12933-024-02266-3

PMID:38715052

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11077732/

Abstract

BACKGROUND

In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization.

MATERIALS AND METHODS

We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately.

RESULTS

The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta.

CONCLUSION

Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

摘要

背景

在观察性和实验性研究中，糖尿病已被报道为主动脉夹层的保护因素。3-羟基丁酸是酮体的主要成分之一，已被发现有利于改善心血管疾病。然而，糖尿病对主动脉夹层的保护作用是否通过 3-羟基丁酸介导尚不清楚。我们旨在通过两阶段孟德尔随机化研究来探讨糖尿病对主动脉夹层风险的因果影响，以及 3-羟基丁酸在其中的中介作用。

材料和方法

我们进行了两阶段孟德尔随机化研究，以研究糖尿病、3-羟基丁酸和主动脉夹层之间的因果关系，并计算 3-羟基丁酸的中介效应。从全基因组关联研究中获得了 1 型糖尿病、2 型糖尿病、主动脉夹层和 3-羟基丁酸的公开可用数据。分别进行了 1 型糖尿病与主动脉夹层的关联、2 型糖尿病与主动脉夹层的关联以及 3-羟基丁酸的中介效应分析。

结果

IVW 法显示 1 型糖尿病与主动脉夹层的风险呈负相关（OR 0.912，95%CI 0.836-0.995），加权中位数、简单模式和加权模式法均得到一致的结果。3-羟基丁酸对 1 型糖尿病与主动脉夹层关系的中介比例为 24.80%（95%CI 5.12-44.47%）。IVW 法显示 2 型糖尿病与主动脉夹层的风险呈负相关（OR 0.763，95%CI 0.607-0.960），加权中位数、简单模式和加权模式法均得到一致的结果。3-羟基丁酸对 2 型糖尿病与主动脉夹层关系无因果中介效应。