During the last five years, an advancement in the treatment of the insulin dependent diabetic patient (Type I) has been the delivery of insulin into the peritoneal space. From our previous studies, five advantages of this insulin delivery route compared to the intravenous and subcutaneous routes have emerged: 1) prolonged insulin delivery catheter patency (more than five years), 2) direct portal vein insulin absorption (direct hepatic insulinzation), 3) decreased peripheral hyperinsulinemia, 4) rapid absorption of intraperitioneal insulin, resulting in normal meal insulin profiles, and 5) normalization of the plasma glucose concentration and glycosylated hemoglobin concentration. Having established the advantages of this route of insulin delivery, we now propose to expand our investigation to specific clinical settings. The grant is divided into three projects: 1) examination of the response and insulin kinetics of intraperitoneally delivered insulin in the fed, postprandial and exercising diabetic patient, 2) long-term follow-up (five years) of insulin-dependent diabetic subjects who have received insulin exclusively by the intraperitoneal route (these patients have all been implanted with our remotely-controlled insulin delivery pump whose insulin delivery catheter terminates in the peritoneal space), and 3) intraperitoneal insulin delivery in a subgroup of insulin-dependent diabetic patients who are resistant to subcutaneous insulin delivery. To safely administer intraperitoneal insulin into these latter patients, we have developed an implantable FDA-approved subcutaneous-peritoneal access device. The proposed studies will carefully define the kinetics of intraperitoneal insulin absorption in insulin-dependent diabetic patients. The long-term benefits to these patients may be the reduction in both microvascular diabetic complications (as a result of normoglycemia) and a reduction in the macrovascular-atherosclerotic complications (as a result of normal insulin profiles). Depending upon the results of the proposed studies, the intraperitioneal delivery of insulin may become the preferred insulin delivery route for specific insulin-requiring diabetic patients.
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