Objective: The wear duration of insulin infusion sets (IIS) is impacted by initial local trauma caused by cannula insertion and sustained inflammation due mostly to insulin infusion, both of which affect insulin absorption. Efforts have been made to mitigate cannula kinking at insertion and during use, and other site reactions that contribute to IIS failures. This Medtronic preclinical study investigated performance of a novel flexible and kink-free soft cannula.
Method: In-vitro tests (included buckling kink test, inflammatory macrophage cell culture, and insulin compatibility test by USP insulin monographic methods) were conducted on the Flexible cannula and commercial Teflon cannulas. In-vivo study of 3-day sets with both cannulas were conducted on diabetic swine by having animals wear one set multiple times (on the abdomen) while receiving Novolog™ insulin subcutaneously via a pump for 7 days or until set failure, determined by (1) blood glucose (BG) value not decreasing by ≥50 mg/dL an hour after a correction bolus for a BG level >350 mg/dL, or (2) evidence of infection at the infusion site.
Result: Compared to the control Teflon cannula, kink resistance of the Flexible cannula was significantly improved (Kinked: Teflon 6/6, Flexible 0/6) . In the inflammatory in-vitro cell culture model, the pro-inflammatory cytokines generated by the Flexible cannula trended less (mean MCP-1: Teflon -9.7 ng/mL, Flexible - 7.7 ng/mL; mean MIP-1α: Teflon -24.1 ng/mL, Flexible - 24.0 ng/mL) . Tested by the USP methods, both cannulas were insulin compatible. In the swine diabetes model, the 3-day IIS with the Flexible cannula had a greater 7-day survival rate (50%, n=10) than the corresponding control (36%, n=56) , although not statistically different. No significant increase in total daily dose of insulin was observed.
Conclusion: Preliminary in-vitro and in-vivo test results indicate that the novel Flexible cannula is ideally suited for IIS device performance. Further product development is ongoing.
C.Chiu: Employee; Medtronic. G.Zhang: Employee; Medtronic. S.Chattaraj: Employee; Medtronic. R.Gottlieb: Employee; Medtronic.