An intravenous cannula will be inserted into the non-dominant hand vein for regular sampling of blood glucose. Samples will be arterialised by inserting the cannula in a retrograde manner and a heated blanket will be used for warming the hand as is standard practice. A second cannula will be inserted into a vein in the antecubital fossa of the same arm for intravenous infusion of glucose and insulin. A modified hyperinsulinaemic glucose clamp will be performed. After a run-in period, arterialised blood glucose will be maintained at 4.5 mmol/L for 30 minutes. Blood glucose will then either be maintained at 4.5 mmol/L throughout (euglycaemia), or lowered over 20 minutes to 2.5 mmol/L (hypoglycaemia), and maintained at this level for 60 minutes. At the end of this experimental phase, euglycaemia (4.5 mmol/L) will be restored and maintained for a further period of 20 minutes. The glucose clamp will then be discontinued and the subjects will be given a meal. Subjects will be advised regarding adjustment of doses and times of insulin administration for the rest of the day by the study doctor who is experienced in the management of insulin-treated diabetes.