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Dose-response relationship between genetically proxied average blood glucose levels and incident coronary heart disease in individuals without diabetes mellitus.

Diabetologia. 2021 Jan 26. doi: 10.1007/s00125-020-05377-0. Epub ahead of print. PMID: 33495845.

Authors/Editors: Burgess S, Malik R, Liu B, Mason AM, Georgakis MK, Dichgans M, Gill D.
Publication Date: 2021



Aims/hypothesis: Our aim was to investigate the relationship between average blood glucose levels and incident CHD in individuals without diabetes mellitus.

Methods: To investigate average blood glucose levels, we studied HbA1c as predicted by 40 variants previously shown to be associated with both type 2 diabetes and HbA1c. Linear and non-linear Mendelian randomisation analyses were performed to investigate associations with incident CHD risk in 324,830 European ancestry individuals from the UK Biobank without diabetes mellitus.

Results: Every one mmol/mol increase in genetically proxied HbA1c was associated with an 11% higher CHD risk (HR 1.11, 95% CI 1.05, 1.18). The dose-response curve increased at all levels of HbA1c, and there was no evidence favouring a non-linear relationship over a linear one.

Conclusions/interpretations: In individuals without diabetes mellitus, lowering average blood glucose levels may reduce CHD risk in a dose-dependent way.


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