To determine whether insulin antibodies are generated in diabetic patients after short- and long-term intraperitoneal insulin use and, if so, whether they are of potential clinical interest. Insulin antibodies commonly develop in diabetic patients who use subcutaneous human insulin, although their clinical significance remains controversial. Few data are available regarding insulin antibody responses to intraperitoneal insulin.


We studied insulin antibody levels and clinical diabetes control in 25 type 1 diabetic patients treated for 3-6 years with intraperitoneal surfactant-stabilized porcine modified human insulin delivered by implantable programmable insulin delivery systems.


All patients had preimplantation insulin antibody levels <20 μU/ml, with a mean value of 2 ± 2 μU/ml (1 SD). Mean antibody levels increased throughout the study period to a mean maximum of 197 ± 326 μU/ml (P < 0.02) with 11 of 25 (44%) patients' levels exceeding 20 μU/ml (insulin responders). The mean time to significant antibody development was 21.8 ± 4.4 months. Of the 11 responder patients, 4 had clinical syndromes that consisted of increasing daily insulin requirements and/or nocturnal hypoglycemia despite minimal nighttime basal insulin infusion rates associated with peak antibody levels >200 μU/ml. None of the nonresponder patients (antibody levels <20 (μU/ml) had these clinical findings.


Our results indicate that insulin antibody levels observed during intraperitoneal administration of human insulin are 1) similar to those reported during subcutaneous administration; although the rise in antibody level may be delayed compared with subcutaneous human insulin, 2) associated with a patient subset who are insulin antibody responders after switching from subcutaneous to intraperitoneal human insulin, 3) associated with a decrease in levels among responder patients regardless of whether they discontinue or continue pump use, and 4) associated with increased insulin needs and/or nocturnal hypoglycemia despite minimal basal rate insulin infusion at nighttime when antibody levels exceed 200 μU/ml.

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