Macrophage activation in type 1 diabetic patients with catheter obstruction during peritoneal insulin delivery with an implantable pump

Abstract

OBJECTIVE - The purpose of this study was to evaluate the activation of macrophages in type 1 diabetic patients during peritoneal insulin delivery with an implantable pump against two types of insulin: that which was collected from the pump reservoir and that which came straight from the bottle (i.e., vial insulin). Macrophage activation was studied in patients with and without catheter obstruction and compared with activation in healthy subjects. RESEARCH DESIGN AND METHODS - Human insulin (21PH, 400 U/ml; Hoescht) was collected from the pump reservoir (Minimed) of diabetic patients with (n = 3) or without (n = 7) catheter obstruction, as assessed by histological examination of the catheter tip. Monocytes were obtained from venous blood samples from both kinds of diabetic patients and from healthy subjects (n = 5) and were differentiated into monocyte-derived macrophages in culture. Their chemotaxis and tumor necrosis factor-α (TNF-α) release were studied with respect to both types of insulin, as previously stated. Formyl-methionyl-leucyl-phenylalanine (fMLP) and lipopolysaccharide (LPS) were used as controls. RESULTS - Neither insulin recovered from the pump reservoir nor vial insulin proved chemotactic to macrophages from either healthy subjects or those diabetic patients with and without catheter obstruction. The migration toward fMLP of macrophages from patients presenting a catheter obstruction was significantly higher than that observed with macrophages from either diabetic patients without obstruction or healthy subjects; the chemotactic index (mean ± SD) was 3.81 ± 0.36 vs. 2.30 ± 0.89 and 2.60 ± 0.80, respectively (P < 0.05). LPS significantly stimulated the TNF-α secretion of macrophages from diabetic subjects with a catheter obstruction, whereas both native and reservoir-recovered insulin had no effect on this release (144.83 ± 67.25 vs, 5.15 ± 2.93 and 5.27 ± 2.43 pg/ml, P < 0.001). CONCLUSIONS - The human insulin used in implantable pumps, regardless of how long it had remained in the pump reservoir, did not induce macrophage activation in diabetic patients treated through intraperitoneal insulin delivery. In some of these diabetic patients, catheter obstruction could be explained by their high capacity of macrophage chemotaxis.