Optimal glycaemic control in unrestrained diabetic dogs using programmed compound squarewave insulin infusions

Abstract

A glycaemic control identical with the normal has been achieved in unrestrained totally depancreatised dogs using a portable open-loop insulin delivery system. The device consisted of a battery power pack with a flow-rate controller, an insulin reservoir and a peristaltic pump from which pulses of insulin were delivered every 90 seconds into the inferior vena cava through an exteriorised indwelling catheter. Insulin was infused at the basal rate of 0.45±0.03 mUkg⁻¹ min⁻¹ (Mean±s.e.m.) in the postabsorptive state resulting in peripheral IRI and plasma glucose levels of 12±1 μU ml⁻¹ and 86±7 mg dl⁻¹. In the postprandial period the infusion rate was enhanced sevenfold to the rate of 3.16±0.21 mU kg⁻¹min⁻¹ for 7h and then reduced to 1.05±0.07 mU kg⁻¹ min⁻¹ for an additional 2.25 h. A weight-maintaining constant diet was provided and the resulting glycaemic profiles were similar to age, sex and weight-matched healthy controls. Fasting peripheral insulin levels in the infused diabetic dogs were not significantly different from non-diabetic controls (10±1μUml⁻¹). However, in the postprandial period of enhanced delivery, insulin levels in the diabetic dogs were 3.1 times higher than the controls. With the compound square waveforms of preprogrammed insulin infusion found appropriate in this study unaccountable low or high plasma glucose levels did not occur but hyperinsulinism accompanied the glycaemic normalisation following a mixed meal.