Hypoglycaemia in diabetes

Hypoglycaemia is a feared and common unwanted effect of diabetes treated with insulin or sulphonylureas, and is the main reason why insulin-treated individuals often fail to achieve the levels of glycaemic control necessary to prevent diabetic complications. Normal brain function depends upon a continuous supply of glucose. If blood glucose falls below normal, interruption of this supply leads to cerebral dysfunction and, if it is not corrected, confusion and coma. Hypoglycaemia chiefly results from the limitation of current subcutaneous insulin delivery, which fails to reproduce the physiology of the pancreatic β-cell, leading to inappropriately high insulin concentrations between meals and at night. Patients are partly protected by physiological defences to hypoglycaemia that ensure release of adrenaline and glucagon as glucose falls below normal, and resist the glucose-lowering effect of insulin. In addition, activation of the sympatho-adrenal system provokes symptoms that patients learn to recognize, and treat by eating or drinking. With increasing duration of diabetes, and following episodes of hypoglycaemia, these defences become impaired and patients are increasingly at risk of severe episodes, particularly if they develop ‘hypoglycaemia unawareness’. Programmes of hypoglycaemia avoidance can reverse unawareness, at least in part, but complete prevention of hypoglycaemia will require completely new approaches to insulin delivery.