Differentiating Associations of Glycemic Traits with Atherosclerotic and Thrombotic Outcomes: Mendelian Randomization Investigation.
American Diabetes Association
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Yuan, S., Mason, A., Burgess, S., & Larsson, S. C. (2022). Differentiating Associations of Glycemic Traits with Atherosclerotic and Thrombotic Outcomes: Mendelian Randomization Investigation.. Diabetes https://doi.org/10.2337/db21-0905
We conducted a Mendelian randomization analysis to differentiate associations of four glycemic indicators with a broad range of atherosclerotic and thrombotic diseases. Independent genetic variants associated with fasting glucose (FG), 2-h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) at the genome-wide significance threshold were used as instrumental variables. Summary-level data for 12 atherosclerotic and 4 thrombotic outcomes were obtained from large genetic consortia and the FinnGen and UK Biobank studies. Higher genetically-predicted glycemic traits were consistently associated with an increased risk of coronary atherosclerosis related diseases and symptoms. Genetically-predicted glycemic traits except HbA1c showed positive associations with peripheral artery disease risk. Genetically-predicted FI levels were positively associated with risk of ischemic stroke and chronic kidney disease. Genetically-predicted FG and 2hGlu were positively associated with the risk of large artery stroke. Genetically-predicted 2hGlu levels showed positive associations with the risk of small vessel stroke. Higher levels of genetically-predicted glycemic traits were not associated with increased risk of thrombotic outcomes. Most associations for genetically-predicted levels of 2hGlu and FI remained after adjusting for other glycemic traits. Increased glycemic status appears to increase risks of coronary and peripheral artery atherosclerosis, but not thrombosis.
Wellcome Trust (204623/Z/16/Z)
External DOI: https://doi.org/10.2337/db21-0905
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337357
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