Reiterated catheter obstructions thwart improved diabetes control with continuous peritoneal insulin infusion (CPII) from implantable pumps (1). Occlusions, from either fibrin clots or omental encapsulations, are promoted by CPII and diabetes duration and insulin instability (2,3). Pathological analysis of encapsulation tissues disclosed, among predominant collagen fibrosis, inflammatory reactions, including lymphocytes and amyloid-like deposits reacting to anti-insulin antibodies, surrounded by histiocytes or giant cells (2). However, catheter obstructions were not related to high plasma anti-insulin antibody levels (4,5). Enhanced migration toward insulin and the chemotactic peptide formyl-methionyl-leucyl-phenylalanine of monocyte-issued macrophages from three patients with previous catheter encapsulations suggested that higher macrophage chemotaxis might promote these events (5). We report two unique observations of aseptic peritonitis with predominant macrophagic reactions that occurred in patients using implantable pumps with recurrent catheter obstructions, supporting this hypothesis.

Case 1 is a 54-year-old woman, type 1 diabetes duration 42 years. After 2 years of CPII, she received an implantable pump (model MIP 2007; MiniMed, Sylmar, CA) in July 2000. In December 2000, a fibrin clot occluding catheter tip was removed using laparoscopy. A shorter replacement catheter was implanted when obstruction recurred in May 2001. Following surgery, CPII was ineffective and ketosis required intravenous insulin delivery. Computerized tomography scanning identified peritoneal fluid accumulation and diffuse thickening of mesenteric fat, suggesting possible neoplasic peritonitis. Laparoscopy revealed diffuse peritoneal inflammation but no cancer node. Neither bacterial infection nor cancer cells were found in peritoneal fluid, but a high content of fibrin, monocytes, lymphocytes, and macrophages were found. The catheter tip stuck to the peritoneum and was surrounded by predominant macrophages among an inflammatory cell reaction. CPII became effective again only after high doses of oral prednisone (1 mg · kg−1 · day−1). Prednisone (15 mg/day) remained necessary to keep CPII effective, with each steroid interruption resulting in recurrent hyperglycemia. No catheter obstruction recurred thereafter.

Case 2 is a 62-year-old man, type 1 diabetes duration 30 years, using CPII since 1981 with previous implantable pump catheter encapsulations from 1990. He received a new implantable pump in December 2000. In June 2002, the catheter encapsulation needed peeling by laparoscopy. Removed tissue showed a predominantly macrophagic inflammatory reaction, including some lymphocytes, giant cells, and pseudo-amyloid material among collagen fibrosis. Catheter obstruction recurred in January 2003. Laparoscopy revealed diffuse peritoneal inflammation with whitish urticaria-like plaques. Pathological analysis identified granulomatous peritoneal lesions with histiocytes, fibrosis, and pseudo-amyloid material unlabeled by anti-insulin antibodies. Similar histiocytic reaction was found in collagen fibrosis surrounding the catheter tip. Prednisone (20 mg/day) was prescribed to treat peritoneal reaction until pump replacement in July 2003 because an unexpected pump failure precluded assessment of steroid effect on CPII efficacy. CPII was effective with the new pump, and prednisone could be stopped 2 weeks after surgery.

In our experience with 87 patients using an implantable pump since 1990, such generalized peritoneal reactions have not been seen previously or reported elsewhere. In both cases, a predominant macrophagic reaction was disclosed, as previously described in encapsulation tissues (2,5). Long-term CPII or diabetes likely promoted these events in patients who appear to be specifically reactive to peritoneal infusion. Because pseudo-amyloid material in Case 2 could not be labeled by anti-insulin antibodies, contribution of insulin in peritoneal macrophagic reaction cannot be argued. We recommend that recurrent implantable pump catheter obstructions should be explored by laparoscopy for peritoneal examination. Although steroid treatment appeared to be effective on peritonitis and restored CPII efficacy, continuation of CPII in such cases must be debated.

Broussolle C, Jeandidier N, Hanaire-Broutin H, the Evadiac Study Group: French multicentre experience with implantable insulin pumps.
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Diabetes Care
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Diabetes Care
Olsen CL, Chan E, Turner DS, Iravani M, Nagy M, Selam JL, Wong ND, Waxman K, Charles MA: Insulin antibody responses after long-term intraperitoneal insulin administration via implantable programmable insulin delivery systems.
Diabetes Care
Kessler L, Tritschler S, Bohbot A, Sigrist S, Karsten V, Boivin S, Dufour P, Belcourt A, Pinget M: Macrophage activation in type 1 diabetic patients with catheter obstruction during peritoneal insulin delivery with an implantable pump.
Diabetes Care