In summary, our study in individuals who had been extensively characterised for metabolic traits provides cohesive evidence to support a hepatic effect of a novel 3′UTR variant in GCK on influencing carbohydrate oxidation, energy expenditure and type 2 diabetes risk; this is consistent with the role of GCK in hepatic glycolysis and energy metabolism. The gene discussed is GCK; the disease is type 2 diabetes mellitus.