Glucose-lowering therapies that are associated with hyperinsulinaemia that is not glucose dependent, such as the SUs and insulin, carry a risk for hypoglycaemia that is increased in older patients, those with longer duration of diabetes, lesser insulin reserve and other comorbidities, including renal impairment, hypothyroidism and defects of counterregulatory hormone secretion. This evidence concerns the gene INS and hypothyroidism.