Endogenous Insulin Delivery on Demand

The autoimmune destruction of pancreatic beta islet cells in type 1 diabetes severely disrupts normal glucose metabolism and causes a chronic and incurable life threatening disease. Treatment with exogenous insulin is life-saving, but requires a complicated daily regimen of multiple injections and blood glucose monitoring. Insulin dosing is adjusted to prevent fluctuations of blood glucose levels to limit episodes of hyperglycaemia. Failure to maintain euglycaemia results in micro- and macrovascular disease and the late complications of diabetes such as nephropathy, retinopathy, hypertension, diabetic ulcers, neuropathy and cardiomyopathy.

The American Diabetes Association recommends a target glycated haemoglobin level of less than seven per cent (HbA1c) as a reflection of consistent euglycemia such that haemoglobin is not abnormally glycated consequent to frequent or prolonged periods of hyperglycaemia. A normal HbA1c is a reliable surrogate predictor of reduced risk of the long term complications of diabetes (1).

While intensive insulin therapy has been encouraged primarily to avoid the delayed complications of diabetes, an intensive insulin regimen in many cases increases the occurrence of hypoglycaemic events (2). The Diabetes Control and Complications Trial reveals that most of the episodes of hypoglycaemia occur when the patient is asleep at night (3). Of great concern too is that, with chronic diabetes, patients frequently become unaware of impending hypoglycaemia, even when they are awake. New methods and devices for insulin delivery and monitoring continue to be developed to improve the management of blood glucose levels. Nevertheless, episodic hypoglycaemia and hypoglycaemic unawareness remain life-threatening risks for a significant number of patients with type 1 diabetes who follow medical advice to normalise their HbA1c level.