Glycemic Regulation Using a Programmed Insulin Delivery Device: III. Long-Term Studies on Diabetic Dogs

Abstract

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 –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- or 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.

Effects of somatostatin added to insulin in a glucose-controlled insulin infusion system

“…Excessive insulin administration is an unavoidable problem with all such peripheral infusion [2,3], particularly post-prandially [4]. Somatostatin infusion has been reported to lower the subcutaneous insulin requirements in insulin dependent diabetics [5,6].…”

Suppression of Growth Hormone and Somatomedin C by Long-Acting Somatostatin Analog SMS 201–995 in Type I Diabetes mellitus

“…Insulin pump devices have almost en abled the euglycemic metabolic control in diabetic patients. However, continuous sub cutaneous insulin infusions promote the de velopment of hyperinsulinemia [1,2] which is considered a possible factor in the patho genesis of macroangiopathy [3]. Moreover, no positive effect of this form of therapy has yet been proved on proliferative retinopathy in its advanced stages.…”

The metabolic and hormonal responses to a mixed meal in umestrained pancreatectomised dogs chronically treated by portal or peripheral insulin infusion

“…Using a portable hormone delivery device, glucose regulation was realised in pancreatectomised dogs for prolonged periods with insulin delivered either into the peripheral [1] or into the portal [2] circulations. To achieve close to normal glycaemic control three simple parameters relating to insulin requirements were programmed.…”