Genetically predicted lower HbA1c was associated with a decreased risk of type 2 diabetes (OR 0.28 per 1% lower HbA1c, 95% CI 0.11–0.71, P = 0.008) and the effect size was smaller in magnitude than the estimate of genetically proxied GK activation, albeit not significant (Pdifference = 0.061). This evidence concerns the gene GK and type 2 diabetes mellitus.