Purpose: For Type 1 diabetic patients, continuous intraperitoneal insulin infusion (CIPII) shows many clinical advantages, including ease of glycemic control, rapid absorption and clearance of insulin, reduced incidence of hypoglycemia, and normalization of the portal to peritoneal insulin gradient. However, the occurrence of intraperitoneal catheter obstruction is problematic according to clinical observations, which may decrease the efficacy of CIPII. Analysis of explanted IP catheters from patients, will be helpful to understand the cause of IP catheter obstructions and will make it possible to develop mitigations to reduce the overall complication rate with CIPII.
Methods: Fixed catheter blockages were removed from explanted (from patients) catheter tips and embedded in paraffin blocks. The following staining methods were used to demonstrate the existence of different major cell types. H&E staining was used to differentiate infiltrated neutrophils, activated macrophages, and giant cells based on cell morphology. Fibrosis is one of the most important steps in the foreign body reaction. One-step trichrome staining was performed to determine the presence of fibroblasts and the formation of any fibrous capsule in/surrounding the catheters. The mast cell populations, which are associated with allergic reactions, were determined using toluidine blue stain. The cause of catheter obstruction may be a result of insulin amyloid formation and thus insulin aggregation, in the form of insulin amyloids, accordingly amyloid red stain was utilized.
Results: Based on the histological evaluation of the blocked samples, the main components of tip blockage were fibroblasts and macrophages. Fibroblasts and macrophages are well-known inflammatory cells, indicating cellular infiltration and fibrotic deposition at the catheter tip end. According to the results of the toluidine blue stain, few mast cells were observed in the blocked samples, which ruled out the possibility of allergic reactions in the formation of tip blockage. A little apple-green birefringence was observed in the amyloid red stained samples under polarized light microscopy. These results indicated that there was a very small amount of amyloid proteins in the tip deposit, which could be insulin amyloid fibrils (Figure 1).
Conclusion: Macrophages and fibroblasts are the main components of the catheter obstruction. Insulin amyloid fibrils may also be involved in tip blockage. Whether the formation of insulin aggregates could accelerate this process by introducing an additional foreign body will be further investigated.
Eric Renard– Professor, Montpellier University Hospital, Montpellier
Peter Lord– CEO, PhysioLogic Devices, Inc., Alpine, California
Diane Burgess– Distinguished Professor of Pharmaceutics, University of Connecticut, Storrs, Connecticut