Pharmacokinetics of intravenous insulin delivery in humans with type 1 diabetes

Insulin pharmacokinetics models describe the distribution and elimination of insulin in the body. These models can be useful in designing infusion schemes to produce a desired plasma insulin profile.

We evaluated the pharmacokinetics of intravenous insulin delivery in five human subjects with type 1 diabetes; one subject was studied on three separate occasions for a total of seven experiments. Each subject consumed an identical 829 Kcal meal of solid food for breakfast and lunch, followed by exercise on a stationary bicycle. Regular human insulin was infused into a peripheral vein at a basal rate (0.5 U/h) for the entire study. Coinciding with the consumption of each meal, insulin was infused at a higher rate for 120 min (average dose 8.5 +/- 2.1 U). The bolus dose was based upon preprandial and 60-min postprandial blood glucose measurements and a sliding scale regimen. Blood glucose levels were allowed to fluctuate throughout the protocol (mean 174 mg/dL, range 55-340 mg/dL). Human insulin levels were measured from plasma samples obtained every 10 min throughout the 8.5-h protocol. A total of 346 plasma samples were assayed to measure the concentration of human insulin.

Data were used to compare (previously developed) insulin kinetics models consisting of one, two, and three first-order linear differential equations. The ability of each model to simulate the input/output data (intravenous insulin infusion rate/plasma insulin concentration) was assessed. Our main finding is that the first-order linear insulin kinetics model was sufficient to describe the clinical data. The model had a fractional insulin loss rate of 0.112 +/- 0.063 min(1) and a distribution volume of 15.6 +/- 4.0 L.