Faster In and Faster Out: Accelerating Insulin Absorption and Action by Insulin Infusion Site Warming

Abstract

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.