Hypoglycaemia in the treatment of diabetes mellitus

Hypoglycaemia (low blood glucose concentration) is the most important acute complication of the pharmacological treatment of diabetes mellitus. Low blood glucose impairs brain (and, potentially, cardiac) function. The brain has minimal endogenous stores of energy, with small amounts of glycogen in astroglial cells. The brain is therefore largely dependent on circulating glucose as the substrate to fuel cerebral metabolism and support cognitive performance. If blood glucose levels fall sufficiently, cognitive dysfunction is inevitable. In health, efficient glucose sensing and counterregulatory mechanisms exist to prevent clinically significant hypoglycaemia. These are impaired by diabetes and by its therapies. Patients with diabetes rank fear of hypoglycaemia as highly as fear of chronic complications such as nephropathy or retinopathy (1). Fear of hypoglycaemia, hypoglycaemia itself and attempts to avoid hypoglycaemia limit the degree to which glycaemic control can be intensified to reduce the risk of chronic complications of diabetes both for type 1 and type 2 diabetes.