GLYCEMIC REGULATION USING A PROGRAMMED INSULIN DELIVERY DEVICE .3. LONG-TERM STUDIES ON DIABETIC DOGS

Long-term glycemic normalization in diabetic dogs has been achieved using a portable insulin delivery device. Six pancreatectomized male dogs carried the device for periods of 7±2 (range 4-12) mo. Pulses of insulin were delivered every 90 s into the inferior vena cava through an exteriorized indwelling catheter. In the postabsorptive period, insulin was infused at the mean rate of 0.44±0.03 mU/min/kg and glycemia was 93±7 mg/dl, while in the postprandial period insulin was infused for 7 h at the mean rate of 3.10±0.22 mU/min/kg. A standard daily diet was provided, and the resulting glycemic profiles were similar to an age-, sex-., and weight-matched group of six healthy controls. Peripheral insulin levels in the infused diabetic dogs (15±1 μU/ml) were not significantly different from nondiabetic controls in the fasting state and were unresponsive to caloric provocation. However, in the postprandial period of enhanced delivery, insulin levels in the diabetic dogs were two to four times higher than in the controls. Unaccountable episodes of hypo- of hyperglycemia did not occur. Techniques for long-term vascular access were developed such that catheter-related complications, including infection and thrombosis, were not encountered. This study demonstrates the feasibility of long-term glycemic control in unrestrained diabetic animals using a preprogrammed waveform of insulin delivery. Hyperinsulinism accompanies the glycemic normalization when the hormone is delivered peripherally.