No abstract

Continuous subcutaneous insulin infusion (CSII) is becoming increasingly used for achieving target glycemic control as well as providing flexibility in lifestyle. In a widely used version of CSII, the insulin pump itself is attached to one end of an insulin infusion set (IIS), which delivers insulin via a thin flexible plastic tube to the patient’s body via a cannula or needle that is inserted under the skin at the other end of the IIS. Despite the increased use of CSII by patients with diabetes, there have been few recent advances in IIS technology, especially when compared to the many recent advances made in insulin pump technology and in insulin pharmacokinetics. To discuss recent developments in, and future plans for IIS development, Diabetes Technology Society virtually hosted the Advances in Insulin Pump Infusion Sets Symposium on December 1, 2020. This symposium featured experts in the field of IISs, including representatives from Medtronic and ConvaTec (which are two manufacturers that are currently developing IISs), Stanford University, Steno Diabetes Center Copenhagen, and Science Consulting in Diabetes. The webinar’s six speakers covered (1) patient burden, (2) extended wear technology, and (3) future directions in IIS development.

Objective: Develop a test methodology for evaluating the reason for infusion set (IS) failure in persons with diabetes using insulin pump therapy (Continuous Sub-cutaneous Insulin Infusion, CSII). Insulin stability (physical, chemical, and microbiological) and/or the loss of preservatives in the infusate are thought to play significant roles in shortening IS wear time. In-vitro and in-vivo methods were used to assess the cause(s) site inflammation and the loss of preservatives. Method: Fast-acting insulin (insulin aspart and lispro) were pumped through different infusion sets (>4) under simulated-use conditions. The pumped insulin and non-pumped insulin controls were characterized for physical, chemical, and microbiological properties. The pumped insulin, combined with fibrinogen (an initiator for material foreign body responses), were tested in murine macrophage cell culture for inflammatory responses. The corresponding infusion sets were tested in vivo in a diabetic porcine model to determine IS wear-time. Result: Pumped insulins in ≥8 insulin/IS combinations met corresponding criteria in USP insulin monographs, indicating no significant chemical changes. Lower preservative content was found to increase insulin aggregates in-vitro/in-vivo. Pro-inflammatory cytokines (MIP-1α, and MCP-1) increased significantly in the inflammatory in-vitro model. The IS wear-time was shortened from 4.9±0.3 days (control) to 1.7±0.3 days (p<0.0001) with lower preservative content (<50% per label claim). Conclusion: Preliminary findings from in-vitro and in-vivo test model development indicate that macrophage number, the inflammatory response, and device wear time were significantly impacted by loss of preservative and trace aggregates/particles. The new test methodology can further our understanding as to how to improve IS wear time. Disclosure S. Chattaraj: Employee; Self; Medtronic. G. Zhang: None. E. Anselmo: Employee; Self; Medtronic. J.C. Fusselman: None.

This study was funded by Medtronic. Declaration of Financial / Other RelationshipsSC, TK, KS, KW and GZ are employees of Medtronic.JME peer reviewers on this manuscript have received an honorarium from JME for their review work, but have no other relevant financial relationships to disclose.The Medtronic Extended-Wear Infusion Set (branded as Medtronic Extended) is a CE marked device in EU, and an investigational device in the US; it is currently not approved for use in the US.

Continuous subcutaneous insulin infusion (CSII) therapy is becoming increasingly popular. CSII provides convenient insulin delivery, precise dosing, easy adjustments for physical activity, stress, or illness, and integration with continuous glucose monitors in hybrid or other closed-loop systems. However, even as insulin pump hardware and software have advanced, technology for insulin infusion sets (IISs) has stayed relatively stagnant over time and is often referred to as the “Achilles heel” of CSII. To discuss barriers to insulin pump therapy and present information about advancements in, and results from clinical trials of extended wear IISs, Diabetes Technology Society virtually hosted the “Improving the Patient Experience with Longer Wear Infusion Sets Symposium” on December 1, 2021. The symposium featured experts in the field of IISs, including representatives from Steno Diabetes Center Copenhagen, University of California San Francisco, Stanford University, Medtronic Diabetes, and Science Consulting in Diabetes. The webinar’s seven speakers covered (1) advancements in insulin pump therapy, (2) efficacy of longer wear infusion sets, and (3) innovations to reduce plastics and insulin waste.