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.