In subjects with type 1 diabetes, autoimmune de-struction of pancreatic β-cells leads eventually to an absolute requirement for insulin replacement therapy. Insulin delivered exogenously is not subject to normal physiological feedback regulation, so it may induce hypoglycemia even in the presence of an intact counterregulatory response. The average individual with type 1 diabetes experiences about two episodes of symptomatic hypoglycemia per week, a figure that has not changed substantially in the last 20 years (1). Severe hypoglycemia (requiring help for recovery) has an annual prevalence of 30–40% and an annual incidence of 1.0–1.7 episodes per patient per year (1). This risk is increased markedly with the increasing duration of the disease and strict glycemic control. In subjects with type 2 diabetes, the increasing duration of the disease and the more widespread use of insulin therapy also increase the risk of severe hypoglycemia. This was reflected in a recent survey in Tayside, Scotland, which found the proportion of severe hypoglycemic episodes needing emergency medical assistance was similar between type 1 and insulin-treated type 2 diabetic patients (2).

The experience of hypoglycemia is not limited to a transient impairment of cognition. We now recognize that hypoglycemia carries with it a recognized morbidity and mortality (3) and creates a negative mood-state characterized by reduced energy and increased tension (4). This may explain why hypoglycemia is greatly feared by individuals with diabetes; so much so that the fear of hypoglycemia is rated with the same degree of concern as the development of sight-threatening retinopathy or end-stage renal disease. This fear of hypoglycemia influences an individual’s ability to adhere to optimal insulin replacement regimens and to put in place those measures required to achieve near-normal glucose control. In this way, hypoglycemia has emerged as a major obstacle to achieving the goals of intensive insulin therapy in everyday clinical practice.