Our results address many of the limitations of prior studies, including the inclusion of bolus and basal preparations of analogue and human insulin, inclusion of a large number of eligible participants from multiple US health care systems, systematic ascertainment of cardiovascular events and CVD mortality, inclusion of a broad representation of adults with type 2 diabetes being treated predominantly in primary care settings, and use of sophisticated analytic methods including but not limited to machine learning. This evidence concerns the gene INS and type 2 diabetes mellitus.