RD Lawrence Lecture 2015 Old habits are hard to break: lessons from the study of hypoglycaemia.

Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia. In the present review, I propose that impaired awareness of hypoglycaemia may represent a form of learning called habituation, a response that, at a cellular level, represents a biological adaptation designed to protect the organism from future exposure to that stressor. In diabetes, this survival response to low glucose is, however, overwhelmed by high systemic insulin levels resulting from exogenous insulin therapy, leading to progressively more severe hypoglycaemia. A recognition of the underlying mechanism means that the development of impaired awareness of hypoglycaemia can perhaps be better understood and explained to individuals with diabetes, and novel therapeutic approaches such as dishabituation or cognitive behavioural therapies can be considered.