Examining the Effect of Supraphysiological Insulin in an In Vitro Insulin Infusion Cannula Host Response Model

Abstract

Continuous subcutaneous insulin infusion (CSII), better known as "pump therapy" is a widely used and relatively effective insulin replacement strategy for individuals living with type 1 diabetes. However, the insulin infusion set (IIS) portion of the pump represents the most signifigant limitation of these devices, with a current wear time of just 2-3 days. Prolonged use of an IIS places individuals at risk for serious adverse events associated with poor glycemic management, including unexplained hyperglycemia and diabetic ketoacidosis. This limitation is often attributed to a local inflammatory host response, which is largely carried out by macrophages that interact with the cannula surface and its adsorbed protein layer. Additional emerging research has demonstrated that the insulin molecule itself can cause significant changes to local tissue which in turn may contribute to impaired IIS performance observed with extended wear time. Here, we present a novel in vitro model used to examine the effect of supraphysiological concentrations of insulin on the inflammatory responses of macrophages to mimic host responses to the IIS. Present data suggests that supraphysiological cocentrations of insulin, like those present at the infusion site, tend to exacerbate the pro-inflammatory macrophage response to IIS cannulas.