Insulin pump therapy and rapid acting insulin: what have we learned?

Approximately 80 years after the discovery and first human use of insulin, we are still striving to replace insulin in a physiological manner. The development of insulin analogues with superior pharmacokinetics has made mimicking of meal and basal insulin requirements by subcutaneous injection more feasible. Administration by continuous subcutaneous insulin infusion (CSII) has provided additional flexibility in meal timing and modifying basal insulin replacement in response to circadian rhythms. Several studies have documented improved glycaemic control with CSII using a rapid-acting analogue such as insulin lispro, compared with regular human insulin. Lower postprandial glucose peaks and improved HbA1c levels were seen with insulin lispro by CSII. In addition, the frequency of hypoglycaemia was significantly reduced and the counter-regulatory hormone responses were maintained. The use of insulin lispro in CSII, compared with regular human insulin, resulted in improved hepatic glucose output in response to glucagon. The potential for problems of hyperglycaemia and ketoacidosis with interruption of insulin delivery by CSII has been studied. One study showed accelerated development of hyperglycaemia and ketosis with insulin lispro compared with regular human insulin while another showed no difference but return to normal glycaemia was faster when insulin lispro was administered. The use of CSII in the US has grown from 6,600 in 1990 to over 100,000 patients currently. With improved insulins, better methods of delivery and advances in glucose monitoring we will continue progress towards physiological insulin replacement and reduce the long-term complications of diabetes.