Mechanisms of impaired awareness of hypoglycaemia: Lessons from neuroimaging

Abstract Hypoglycaemia is a physiological stress and the body generates symptom and hormonal responses that alert the individual and protect them. Protection from hypoglycaemia requires three layers of defence. Firstly, a physiological counter‐regulatory response that is designed to correct glucose through glycogenolysis and gluconeogenesis; secondly awareness—the ability to perceive symptoms and attribute them to hypoglycaemia; and thirdly a behavioural and emotional response that serves as motivation to avoid subsequent episodes. Impaired awareness of hypoglycaemia (IAH) affects up to a third of people with type 1 diabetes and increases the risk of severe hypoglycaemia. The traditional model of IAH suggests this is a physiological habituation response caused by recurrent episodes that can be reversed on meticulous avoidance of hypoglycaemia. Recent data, especially from neuroimaging, suggests important roles for regions of the brain involved in salience, attention and interoception, implying a more nuanced view of IAH that may involve deficits in each of these areas. This may explain why simple hypoglycaemia avoidance using technology may not suffice to restore awareness, requiring a more holistic approach that addresses key cognitive barriers.