Faster in and faster out: Accelerating insulin absorption and action by insulin infusion site warming

摘要

Objective: This study was undertaken to investigate the effect of an insulin infusion site warming device, the InsuPatch40 ? (IP40) (InsuLine Medical Ltd., Petach-Tikvah, Israel), on insulin aspart pharmacodynamics (PD) and pharmacokinetics (PK) in adolescents with type 1 diabetes. Subjects and Methods: Seventeen subjects with type 1 diabetes (age, 15±1 years; hemoglobin A1c, 7.5±0.2% [58±2.2 mmol/mol]) underwent two euglycemic clamps performed on separate mornings with and without IP40 activation with warming temperature at 40 C. On both days, the basal infusion was suspended, and glucose levels were maintained between 90 and 100 mg/dL by a variable rate dextrose infusion for up to 5 h after a 0.2 U/kg bolus of insulin aspart. Results: Time to peak insulin action and time to half-maximal action occurred earlier with a greater early glucodynamic effect (area under the curve [AUC] for glucose infusion rate from 0 to 30 min) with IP40 than without the IP40, whereas the AUC for the time-action profile and the peak action did not differ with and without infusion site warming. PK parameters were in agreement with PD parameters, namely, a significantly earlier time to reach the maximum increment in insulin concentrations and greater early bioavailability (AUC for the change in insulin concentration from 0 to 30 min) with the IP40. The tail of the plasma insulin response curve was also shortened with infusion site warming, with the time to reach baseline insulin concentration occurring significantly earlier (P=0.04). Conclusions: Our data demonstrate that skin warming around the infusion site to 40 C with the IP40 is an effective means to accelerate absorption and action of rapid-acting insulin. These improvements in time-action responses have the potential to enhance the performance of open- and closed-loop insulin delivery systems.