While in-depth mechanistic investigations of the cholesin-GPR146 network could not be reliably performed in tissues from patients undergoing cardiovascular surgeries that we investigated, this is the first report to demonstrate that the activity of this ligand-receptor pair is likely not restricted to the intestine-liver axis and shows strong associations with a number of important clinical metabolic traits and aspects of diabetes treatment. This evidence concerns the gene GPR146 and diabetes mellitus.