Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods

Aims/hypothesis. We compared four methods to assess their accuracy in measu ring insulin secretion during an intravenous glucose tolerance test in pati ents with Type II (non-insulin-dependent) diabetes mellitus and with varyin g beta-cell function and matched control subjects. Methods. Eight control subjects and eight Type II diabetic patients underwe nt an intravenous glucose tolerance test with tolbutamide and an intravenou s bolus injection of C-peptide to assess C-peptide kinetics. Insulin secret ion rates were determined by the Eaton deconvolution (reference method), th e Insulin SECretion method (ISEC) based on population kinetic parameters as well as one-compartment and two-compartment versions of the combined model of insulin and C-peptide kinetics. To allow a comparison of the accuracy o f the four methods, fasting rates and amounts of insulin secreted during th e first phase (0-10 min) and the second phase (10-180 min) were calculated. Results. All secretion responses from the ISEC method were strongly correla ted to those obtained by the Eaton deconvolution method (r = 0.83-0.92). Th e one-compartment combined model, however, showed a high correlation to the reference method only for the first-phase insulin response (r = 0.78). The two-compartment combined model failed to provide reliable estimates of ins ulin secretion in three of the control subjects and in two patients with Ty pe II diabetes. The four methods were accurate with respect to mean basal a nd first.-phase secretion response. The one-compartment and two-compartment combined models were less accurate in measuring the second-phase response. Conclusion/interpretation. The ISEC method can be applied to normal, obese or Type II diabetic patients. In patients with deviating kinetics of C-pept ide the Eaton deconvolution method is the method of choice while the one-co mpartment combined model is suitable for measuring only the first-phase ins ulin secretion.