PERITONEAL AND SUBCUTANEOUS ABSORPTION OF INSULIN IN TYPE-I DIABETIC SUBJECTS

We and others have shown that in type I diabetes, ip insulin delivery results in lower free insulin levels than sc delivery. The aim of this study was to compare the rate of appearance of insulin in the periphe ral circulation during ip and sc insulin administration in type I diab etes, in steady state and nonsteady state. To do this, we determined f ree insulin levels during ip or sc infusion as well as the impulse res ponse of the insulin system after iv injection of a 6-nmol bolus of in sulin. Twelve hours after a constant basal insulin infusion (5.5 +/- 1 .4 nmol/h) was started, five C-peptide-negative type I diabetic subjec ts showed a lower systemic rate of appearance of insulin (expressed as a percentage of the administered dose) with ip than sc administration (27 +/- 6% vs. 40 +/- 10%; P < 0.001). In nonsteady state, when the i nfusion rate was increased from basal to 15 nmol/h (0-150 min) and sub sequently to 42 nmol/h (150-300 min), the percent increase in insulin' s systemic rate of appearance was higher with ip than sc infusion (P < 0.05 from 60-150 min; P < 0.01 from 150-300 min), indicating faster a bsorption. Thus, we conclude that insulin is more rapidly absorbed fro m the peritoneal cavity than from sc tissue. However, with ip administ ration, a sizable amount of insulin, once absorbed, is extracted befor e reaching the peripheral circulation, most likely by the liver. This is indirect evidence that ip insulin delivery results in a portal-peri pheral insulin gradient in humans.