Hyperglycemia due to insulin deficiency alone, such as with endocrine cell destruction in type 1 diabetes (T1D), reflects decreased insulin output with normal or increased sensitivity, whereas hyperglycemia due to insulin-resistant states (such as in T2D) can be accompanied by either increased insulin output (because of ‘compensation’ by cells that produce insulin) or decreased insulin output (failed compensation). This evidence concerns the gene INS and type 1 diabetes mellitus.