INSULIN SECRETORY PROFILES AND C-PEPTIDE CLEARANCE KINETICS AT 6 MONTHS AND 2 YEARS AFTER KIDNEY-PANCREAS TRANSPLANTATION

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. 5.1 +/- 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.