Basal rate subcutaneous insulin infusion: absorption kinetics and relation to local blood flow

Twenty diabetic patients received a constant subcutaneous infusion of 125I-labelled short-acting insulin (1.12 U/h) into the anterior abdominal wall. Measurement of the size of the insulin depot at the infusion site was performed by measuring the radioactivity and by using a calibration bolus to transform count rate to units of insulin in the depot. By the 133Xenon technique, local subcutaneous blood flow rate was measured on the contralateral side of the anterior abdominal wall. From the start of the infusion the SC depot built up slowly, but did not reach steady-state by 6 h. After 24 h of infusion, the size of the depot ranged between 2.7 and 10.9 U (5.2 +/- 0.5 U, mean +/- SE). The size of this steady-state depot was inversely correlated with SC blood flow. After stopping the infusion, insulin disappeared according to first order kinetics without any lag period. The insulin disappearance rate from the depot was positively correlated with the blood flow in a curvilinear fashion. The results suggest that the relationship between blood flow and the size of the insulin depot is best explained by a predominantly blood flow limited removal of insulin at low rates of blood flow, with increasing limitation by diffusion at higher rates.