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

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 HbA _1c as predicted by 40 variants previously shown to be associated with both type 2 diabetes and HbA _1c . 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 HbA _1c 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 HbA _1c , 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.