Iatrogenic hypoglycaemia is a well-known complication of insulin therapy in patients with diabetes mellitus and a limiting factor for glycaemic control. In a setting of endogenous insulin deficiency (type 1 and advanced type 2 diabetes), one episode of hypoglycaemia reduces
both counterregulatory hormone responses to and subjective awareness of subsequent hypoglycaemia, thus
impairing physiological defences against hypoglycaemia.
This phenomenon may lead to a vicious cycle of recurrent hypoglycaemia and glucose counterregulatory
failure, of which hypoglycaemia unawareness (i.e. the
inability to perceive symptoms of hypoglycaemia) is the
clinical representative. The underlying mechanism of
hypoglycaemia-induced counterregulatory failure has not
yet been disclosed. Patients with clinical hypoglycaemia
unawareness are at high risk of severe hypoglycaemia
that requires third-party assistance. Management options
include avoidance of hypoglycaemic events and optimisation of insulin therapy to limit deterioration of glycaemic control associated with hypoglycaemia avoidance. Several counterregulatory-stimulating agents have been found to improve hypoglycaemic awareness in small clinical trials, but none have been tested in sufficiently large randomised studies to justify their use in daily practice. More research is required to elucidate the pathogenesis of counterregulatory failure and to develop adequate treatment strategies.