Insulin Secretory Profiles and C-Peptide Clearance Kinetics at 6 Months and 2 Years After Kidney-Pancreas Transplantation

Abstract

Glucose, insulin secretion, and insulin secretory pulses were measured by deconvolution of peripheral C-peptide concentrations in 10 IDDM recipients of a combined kidney-pancreas allograft 6 mo post-transplantation and were compared with 10 matched nondiabetic control subjects. Seven of the 10 recipients were restudied 2 yr post-transplantation. To control for immunosuppressive therapy, 6 patients with a kidney allograft also were studied. Pancreatic insulin secretion rates were evaluated over a 24-h period with three mixed meals. Six months post-transplantation, fasting (5.3 ± 0.1 vs. 5.3 ± 0.1 mM), average 24-h (6.0 ± 0.1 vs. 5.7 ± 0.1 mM), and meal-related (6.1 ± 0.3 vs. 5.8 ± 0.2 mM) plasma glucose levels were not different in control subjects and recipients, respectively. Total 24-h insulin secretion rates were similar between the two groups (150 ± 15 vs. 182 ± 24 nmol · m−2 · 24 h−1). However, post-transplantation, the relationship between basal and meal-stimulated insulin secretion was altered with increased basal insulin secretion (52.2 ± 6.4 vs. 97.4 ± 12.5 pmol · m−2 · min−1 P < 0.004) and reduced meal-related secretion. The proportion of total 24-h insulin secretion comprised by basal secretion was 44 ± 4% in the control subjects vs. 73 ± 5% in recipients. The number of ultradian oscillations of insulin secretion identified in each 24-h period by pulse analysis was similar in control subjects and recipients (11.9 ± 0.9 vs. 10.4 ± 0.5 oscillations/24 h). Two years post-transplantation, the glucose profiles and oscillatory insulin secretory patterns remained intact. Basal insulin secretion was 76 ± 11 pmol · m−2 · min−1 and 24-h insulin secretion was 167 ± nmol m−2 24 h−1. Six kidney-transplant recipients studied showed that 47 ± 3% of 24-h insulin secretion was basal secretion. This finding supported the idea that altered meal secretory patterns observed in the kidney-pancreas recipients were not the result of immunosuppressive therapy. After combined kidney-pancreas transplantation 1) plasma glucose profiles remain normal 2 yr post-transplantation, 2) clearance of C-peptide is reduced, 3) basal insulin secretion is increased but meal responses are reduced, and 4) the normal oscillatory pattern of insulin secretion persists.