Comparison of pancreas-transplanted type 1 diabetic patients with portal-venous versus systemic-venous graft drainage: impact on glucose regulatory hormones and the growth hormone/insulin-like growth factor-I axis.

Context: Pancreas grafts can be drained through the iliac vein (systemic drainage) or the portal vein.

Objective: We hypothesized that normalization of portal insulin in patients with portal pancreas graft drainage stimulates the GH/IGF-I axis and thereby contributes to glucose control.

Methods: We compared patients after combined kidney and pancreas transplantation with portal drainage (n = 7) to patients with systemic drainage of the pancreas graft (n = 8) and nondiabetic controls (n = 8). Overnight fasting sera were analyzed for free and total IGF-I and IGF-binding proteins. Glucose regulatory hormones were examined after an oral glucose tolerance test and GH after stimulation with GHRH.

Results: Systemic drainage led to higher basal and stimulated insulin levels than portal drainage (P < 0.05), but increments in response to oral glucose were reduced in both transplanted groups (P < 0.05 vs. controls). However, glucose tolerance was similar in all groups. Circulating free and total IGF-I and IGF-binding protein-3 were similar to control levels in the systemic drainage group but elevated in the portal drainage group (P < 0.05). Consistently, the GH response was reduced in the portal drainage group (P < 0.05 vs. controls) and correlated inversely with free IGF-I (r = -0.63, P < 0.05).

Conclusion: Portal drainage of pancreatic endocrine secretion in pancreas graft recipients raises IGF-I and lowers GH secretion. These changes might explain that glucose regulation is maintained despite lower peripheral insulin levels, compared with patients with systemic graft drainage and nondiabetic control subjects.