With incidences of approximately 2 per patient per week [4–6] for mild (i.e. self-treated) hypoglycemia, and 0.1-1.5 per patient year [2, 5–9] for severe hypoglycemia (SH), hypoglycemia is both the main limitation in achieving glycemic targets and the main side effect of intensified insulin therapy in T1DM [10, 11]. The gene discussed is INS; the disease is Hypoglycemia.