PANCREATIC POLYPEPTIDE (PP) ADMINISTRATION REDUCES THE INSULIN REQUIREMENT OF PATIENTS ON INSULIN PUMP TREATMENT

Abstract

Introduction: PP deficiency has been shown to be associated with hepatic insulin resistance in chronic pancreatitis (CP) and after pancreatectomy. Our previous studies with an 8 hr infusion of bovine PP (bPP) in patients with severe CP showed enhanced insulin action and improved glucose tolerance. We therefore sought to determine whether the addition of a continuous infusion of bPP would reduce the insulin requirements in patients on stable insulin pump treatment of diabetes. Methods: We studied 3 diabetic patients (2 with long standing auto-immune type 1 diabetes and one with total pancreatectomy), who were stable on outpatient insulin pump therapy (variable basal rate with bolus additions based on frequent finger-stick glucose determinations). In a single-blind cross-over design, a continuous, fixed subcutaneous infusion of 2 pmol·kg·min bPP or saline was begun, and insulin requirements and glucose levels were monitored for 72 hrs. Mean plasma glucose [G] determination and mean insulin infusion [Ii] requirements were assessed during each 24 hrs of the infusion period. Results: There were no adverse outcomes or side effects associated with the 72 hr bPP infusion in any patient. In two patients, the insulin pump was turned off completely, as per standard protocol, when [G] fell below 60 mg/dl after 48 hrs of bPP infusion. The pump was restarted, per protocol, when [G] climbed above 100 mg/dl 8 hrs later. During the final 24 hrs of bPP infusion, [G] was 211 mg/dl, and mean [Ii] was 3.81 U/hr, compared to the final 24 hr of saline infusion (197 mg/dl and 4.10 U/hr, respectively). The insulin need, corrected for [G], or [Ii]/[G], decreased 15.1% during bPP infusion compared to saline. Conclusions: These preliminary data suggest that the addition of a 2 pmol·kg·min subcutaneous infusion of bPP to patients on stable insulin pump treatment of diabetes resulted in a lowered insulin requirement. This effect corroborates earlier findings of a therapeutic effect of an 8 hr infusion of bPP, and suggests that PP replacement may benefit patients with profound endocrine insufficiency, by enhancing sensitivity to insulin. These effects may be of value in delaying or reducing insulin therapy in patients with PP deficiency due to CP or pancreatectomy.