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Vitamins and plant ingredients

Effects of selenium on coronary artery disease, type 2 diabetes and their risk factors: a Mendelian randomization study

European Journal of Clinical Nutrition volume 75, pages 1668–1678 (2021)Cite this article

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Abstract

Background

The impact of selenium on coronary artery disease (CAD) and type 2 diabetes (T2D) remains unclear with inconsistent results from observational studies and randomized controlled trials. We used Mendelian randomization to obtain unconfounded estimates of the effect of selenium on CAD, T2D, lipids and glycemic traits.

Methods

We applied genetic variants strongly (P < 5 × 10−8) associated with blood and toenail selenium to publicly available summary statistics from large consortia genome-wide association studies of CAD (76,014 cases and 264,785 non-cases), T2D (74,124 cases and 824,006 controls), lipids and glycemic traits. Variant specific Wald estimates were combined using inverse variance weighting, with several sensitivity analyses.

Results

Genetically predicted selenium was associated with higher T2D (OR 1.27, 95% CI 1.07–1.50, P = 0.006). There was little evidence of an association with CAD. Genetically predicted selenium was associated with lower low-density lipoprotein (LDL) cholesterol, lower high-density lipoprotein (HDL) cholesterol, higher fasting insulin and higher homeostasis model assessment of insulin resistance. These results were not robust to all sensitivity analyses. No associations with triglycerides, fasting glucose or homeostasis model assessment of β-cell function were evident.

Conclusions

Our study suggests selenium may increase the risk of T2D, possibly through insulin resistance rather than pancreatic beta cell function, but may reduce lipids. We found little evidence of an association with CAD, although an inverse association cannot be definitively excluded. The effect of selenium on these outcomes warrants further investigation.

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Acknowledgements

Data on coronary artery disease/myocardial infarction have been contributed by the CARDIoGRAMplusC4D and UK Biobank CardioMetabolic Consortium CHD working group who used the UK Biobank Resource (application number 9922). Data have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. Data on diabetes have been contributed by DIAGRAM investigators and have been downloaded from http://www.diagram-consortium.org. Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org.

Funding

The authors received no funding for this study.

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Authors and Affiliations

  1. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Patrick Manson Building, 7 Sassoon Road, Pokfulam, Hong Kong SAR, China

    Abigail A. Rath & C. Mary Schooling

  2. Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, 6/F Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

    H. Simon Lam

  3. School of Public Health and Health Policy, City University of New York, New York City, NY, USA

    C. Mary Schooling

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AAR and CMS designed the study, analyzed the data, interpreted the results and had primary responsibility for the final content. AAR drafted the paper. CMS critically revised the paper. HSL reviewed and commented on the paper.

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Correspondence to C. Mary Schooling.

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Rath, A.A., Lam, H.S. & Schooling, C.M. Effects of selenium on coronary artery disease, type 2 diabetes and their risk factors: a Mendelian randomization study. Eur J Clin Nutr 75, 1668–1678 (2021). https://doi.org/10.1038/s41430-021-00882-w

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