Abstract

The Yale Ultra-Fast Acting Insulin Project was undertaken to explore ways to accelerate the time action profiles of rapid-acting insulin analogs to improve performance of closed and open-loop insulin delivery. With the euglycemic clamp technique, we previously reported that warming the skin around the insulin infusion site to 38.5ºC with the InsuPatch (IP38.5) results in an earlier time to peak insulin action (T GIRmax ) as compared to control clamps without IP activation (No IP) for a 0.2 unit/kg bolus of aspart insulin. To examine whether the time action profile of aspart insulin could be accelerated further by increasing IP temperature to 40ºC (IP40), paired clamps (IP40 vs. No IP) using the identical protocol have been performed in 5 adolescents with type 1 diabetes (T1D) and results compared to those in 13 adolescents with T1D previously studied with IP38.5. There were no significant differences in the maximum glucose infusion rate (GIRmax) or the overall area under curve for GIR (AUCGIR 0-300min) between IP40, IP38.5 and No IP. In contrast, skin warming with IP40 and IP38.5 reduced the time to reach half maximum (Tearly50%) and maximum GIR (TGIRmax) and increased AUC GIR 0-90min; effects that were greater with IP40 vs. IP38.5. Our preliminary results indicate that skin warming accelerates the early pharmacodynamic action of subcutaneously injected insulin and suggest that the effect is accentuated by increasing the warming temperature within the approved range for skin warming devices.