INSULIN-SECRETION RATES ESTIMATED BY 2 MATHEMATICAL-METHODS IN PANCREAS-KIDNEY TRANSPLANT RECIPIENTS

After pancreas-kidney transplantation, it is difficult to obtain an ac curate estimate of the insulin secretion of the pancreas graft, since several pitfalls are involved using peripheral C-peptide and/or insuli n measurements in this determination. In this study, the individual ki netic parameters of C-peptide and then the rates of insulin secretion were estimated by two mathematical methods, the deconvolution method a nd the ''combined model'' during slow (oral glucose) and fast (intrave nous glucagon) changes in insulin secretion in six successful pancreas -kidney transplant recipients with systemic delivery of insulin (Pr), six nondiabetic kidney-transplant recipients with portal insulin secre tion (Kx), six nondiabetic controls (NS), and six C-peptide-negative i nsulin-dependent diabetes mellitus patients (IDDM). Decreased C-peptid e clearance and basal and poststimulatory hyperinsulinemia were found in both Pr and Kx compared with NS (P < 0.05). Similar glucose respons es were observed after intravenous glucagon in all groups, whereas the responses after oral glucose were 30% higher in Pr and Kx than in NS (P < 0.05). During oral glucose and after intravenous glucagon, both m athematical methods resulted in significantly lower maximal and increm ental insulin secretion rates (ISR) in Pr than in Kx (P < 0.05). In co ntrast, calculations of incremental ISR in NS and Pr induced by the tw o p-cell stimuli were about the same but significantly higher in Kx th an in NS (P < 0.05). These results differed markedly from those obtain ed using peripheral measurements of insulin and C-peptide alone. In co nclusion, when C-peptide clearance and insulin metabolism change, such as in pancreas-kidney transplant recipients, accurate evaluation of i nsulin secretion from the graft can be obtained only by using individu al kinetics of the peptides before calculating the ISR. This study als o clearly demonstrates that insulin secretion after pancreas transplan tation is still defective.