Dose-response relationship between genetically proxied average blood glucose levels and incident coronary heart disease in individuals without diabetes mellitus.
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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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1432-0428
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European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
European Commission Horizon 2020 (H2020) Societal Challenges (667375)
Medical Research Council (MC_UU_00002/7)