CIRCULATING PROINSULIN LEVELS IN INSULIN-DEPENDENT DIABETIC-PATIENTS AFTER WHOLE PANCREAS-KIDNEY TRANSPLANTATION

Disproportional hyperproinsulinemia is a sensitive marker for beta-cel l dysfunction. The objective of this study was to assess the proinsuli n profile in persons with insulin-dependent diabetes mellitus (IDDM) a fter pancreas-kidney transplantation. We determined serum insulin, C-p eptide, and proinsulin concentrations during an oral glucose challenge in five pancreas-kidney transplant recipients, nine nondiabetic kidne y transplant recipients, and 17 normal subjects. Basal proinsulin conc entrations were significantly increased iri pancreas-kidney recipients (geometric mean [+/-1 SE range], 6.0 [5.5 to 6.4] pmol/L) and kidney recipients (6.4 [5.4 to 7.5] pmol/L) compared with the normal subjects (2.8 [2.5 to 3.2] pmol/L). Integrated proinsulin concentrations durin g the oral glucose load were also higher in pancreas-kidney recipients (1.4 [1.1 to 1.8] nmol/L min) and kidney recipients (1.5 [1.2 to 2.0] nmol/L min) versus normal subjects (0.8 [0.7 to 0.9] nmol/L min). The re was no difference in basal or integrated proinsulin concentrations between the two transplant groups. Even after adjustment for the glome rular filtration rate (GFR), basal and incremental proinsulin concentr ations continued to be higher in the transplant groups than in the nor mal subjects. Proinsulin to C-peptide molar ratios both before and aft er the glucose load were similar in the three groups. From these findi ngs, we conclude that pancreas-kidney transplantation provokes proport ional hyperproinsulinemia, which is closely associated with its reduce d clearance in the kidneys. Copyright (C) 1998 by W.B. Saunders Compan y.