Maintenance of normoglycemia in pancreatectomized dogs with a controlled release micropump

A diffusion-based insulin micropump was capable of sustaining normoglycemia in diabetic, pancreatectomized dogs for as long as 10 months. Basal insulin delivery was provided by diffusion into the peritoneal cavity from the insulin reservoir across a silicone rubber porous outlet, while the delivery of insulin was augmented for 35 minutes at mealtimes by repeated squeezing of a polyurethane foam disk; the latter was initiated 15 minutes prior to the start of the meal. In the best implant, which functioned for more than 10 months before it was deliberately terminated, the mean glucose level was 126 +/- 24.7 mg/dl (+/- SD) and the mean Schlichtkrull M value was 2.8. In the other three implants, the mean and standard deviations were a little higher. The basal insulin supply was sufficient to restore normoglycemia each morning, while the augmented supply substantially reduced the size of the postprandial period of hyperglycemia. Over the 10 month period studied, the maximum concentration was 150 mg/dl approximately 6 hours after the beginning of the meal, based on the mean of the approximately 200 glucose profiles determined for this implant. Despite this ability to maintain reasonable normoglycemic profiles for long periods, the pump performance deteriorated over this time period, presumably from a tissue reaction to the porous outlet of the implant. This deterioration was evident in the higher levels of glycemia associated with an insulin delivery program that was maintained for too long or in the need to readjust the program to achieve similar levels of glycemia. Nevertheless, the biocompatibility and efficacy of the controlled release micropump demonstrates the feasibility of this approach.