Causal effects of genetically predicted type 2 diabetes mellitus on blood lipid profiles and concentration of particle-size-determined lipoprotein subclasses: a two-sample Mendelian randomization study

Publication type

Journal Article

Authors

Publication date

October 13, 2022

Summary:

Background: Observational studies have shown inconsistent results of the associations between type 2 diabetes mellitus (T2DM) and blood lipid profiles, while there is also a lack of evidence from randomized controlled trials (RCTs) for the causal effects of T2DM on blood lipid profiles and lipoprotein subclasses.

Objectives: Our study aimed at investigating the causal effects of T2DM on blood lipid profiles and concentration of particle-size-determined lipoprotein subclasses by using the two-sample Mendelian randomization (MR) method.

Methods: We obtained genetic variants for T2DM and blood lipid profiles including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) from international genome-wide association studies (GWASs). Two-sample MR method was applied to explore the potential causal effects of genetically predicted T2DM on blood lipid profiles based on different databases, respectively, and results from each MR analysis were further meta-analyzed to obtain the summary results. The causal effects of genetically predicted T2DM on the concentration of different subclasses of lipoproteins that are determined by particle size were also involved in MR analysis.

Results: Genetically predicted 1-unit higher log odds of T2DM had a significant causal effect on a higher level of TG (estimated β coefficient: 0.03, 95% confidence interval [CI]: 0.00 to 0.06) and lower level of HDL-C (estimated β coefficient: −0.09, 95% CI: −0.11 to −0.06). The causality of T2DM on the level of TC or LDL-C was not found (estimated β coefficient: −0.01, 95% CI: −0.02 to 0.01 for TC and estimated β coefficient: 0.01, 95% CI: −0.01 to 0.02 for LDL-C). For different sizes of lipoprotein particles, 1-unit higher log odds of T2DM was causally associated with higher level of small LDL particles, and lower level of medium HDL particles, large HDL particles, and very large HDL particles.

Conclusion: Evidence from our present study showed causal effects of T2DM on the level of TG, HDL-C, and concentration of different particle sizes of lipoprotein subclasses comprehensively, which might be particularly helpful in illustrating dyslipidemia experienced by patients with T2DM, and further indicate new treatment targets for these patients to prevent subsequent excessive cardiovascular events from a genetic point of view.

Published in

Frontiers in Cardiovascular Medicine

Volume

Volume: 9:965995

DOI

https://doi.org/%2010.3389/fcvm.2022.965995

ISSN

2297055

Subjects

Notes

Open Access

© 2022 Chen, Zheng, Shao, Zhou, Yang, Huang and Tang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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