HYPERINSULINEMIA AFTER PANCREATIC TRANSPLANTATION - PREDICTION BY A NOVEL COMPUTER-MODEL AND IN-VIVO VERIFICATION

Objective The authors evaluated systemic venous insulin release as a c ause of the hyperinsulinemia (HINS) associated with pancreatic transpl antation (PTX) with respect to the mechanism and metabolic consequence s. Summary Background Data Many investigators believe the postoperativ e anatomy associated with common PTX techniques to be the sole cause o f the two- to threefold posttransplantation HINS. However, this concep t remains to be conclusively proved and characterized quantitatively. Methods The authors used three approaches to achieve their objectives. First, a computer model was generated based on established data conce rning blood flow and tissue insulin extraction to determine whether it was mathematically possible for HINS to be caused by systemic insulin release. Second, HINS clamps were applied to normal dogs using the An dres clamp technique to quantify the in vivo differences in peripheral insulin levels and the metabolic consequences of systemic versus port al insulin infusion. Third, prolonged insulin half-life was evaluated as a possible mechanism of HINS from systemic insulin release by deter mination of biexponential rates of plasma disappearance from an endoge nous pulse of insulin in surgically induced dog models of systemic and portal insulin release. Results First, the computer model calculated a 1.4- to 2.9-fold increase in peripheral venous insulin levels with s ystemic versus portal insulin release, verifying mathematically the co ncept of HINS resulting from systemic insulin release. Second, the act ual systemic insulin infusion produced a 1.3- to 1.4-fold increase in peripheral venous insulin levels compared with portal infusion (p < 0. 05). No significant differences in hepatic glucose output, total gluco se disposal, or glucose infusion requirements were seen. Third, althou gh the basal insulin level was twofold higher in the surgically induce d animal models with systemic insulin release (p < 0.003), there were no differences in biexponential insulin clearance parameters. Conclusi ons The HINS produced by systemic insulin release did not significantl y alter glucose metabolism and was not the result of altered periphera l insulin clearance parameters. In vivo systemic venous insulin infusi on studies produce HINS, but not to the degree calculated by mathemati c modeling or that occurs after clinical PTX, making it likely that ot her factors also play a role in the HINS after PTX.