Insulin responses to varying profiles of subcutaneous insulin infusion: kinetic modelling studies

Abstract

Refinement of continuous subcutaneous insulin infusion for diabetes therapy requires improved knowledge of subcutaneous insulin absorption kinetics. We have used kinetic modelling to quantitate systemic insulin delivery produced by subcutaneously-infused insulin (i.e. simulated meal and basal delivery). Profiles were studied in normal subjects, with endogenous insulin suppressed. Paired studies of intravenous insulin infusion enabled systemic insulin delivery to be quantitated. High rate subcutaneous delivery (10 U in 5 min) resulted in a systemic delivery of approximately 8 U in 4h. Increasing infused insulin concentration delayed systemic delivery (p<0.025). Both continuous and pulsatile low-rate infusions (2.4 U/h) gave similar slow increases in systemic delivery to 1 U after 4 h. Computer fitting to a two-pool model of the subcutaneous space suggested a low rate of insulin degradation for all profiles (rate constant <10%/h). We conclude that: (1) systemic insulin delivery following subcutaneous infusion conforms reasonably to a two-pool model, (2) subcutaneous insulin degradation is low regardless of input profile, (3) a long delay in basal systemic delivery should be taken into account when initiating or resuming interrupted subcutaneous insulin infusion. Kinetic modelling of subcutaneous insulin absorption should be useful to predict the impact of programming strategies for continuous subcutaneous insulin infusion therapy.