Performance of individually measured vs population-based C-peptide kinetics to assess β-cell function in the presence and absence of acute insulin resistance

Aims: To compare the performance of population-based kinetics with that of directly measured C-peptide kinetics when used to calculate β-cell responsivity indices, and to study people with and without acute insulin resistance to ensure that population-based kinetics apply to all conditions where β-cell function is measured. Methods: Somatostatin was used to inhibit endogenous insulin secretion in 56 people without diabetes. Subsequently, a C-peptide bolus was administered and the changing concentrations were used to calculate individual kinetic measures of C-peptide clearance. In addition, the participants were studied on 2 occasions in random order using an oral glucose tolerance test (OGTT). On one occasion, free fatty acid elevation, to cause insulin resistance, was achieved by infusion of Intralipid + heparin. The Disposition Index (DI) was then estimated by the oral minimal model using either population-based or individual C-peptide kinetics. Results: There were marked differences in the exchange variables (k₁₂ and k₂₁) of the model describing C-peptide kinetics, but smaller differences in the fractional clearance; that is, the irreversible loss from the accessible compartment (k₀₁), obtained from population-based estimates compared with experimental measurement. Because it is predominantly influenced by k₀₁, DI estimated using individual kinetics correlated well with DI estimated using population-based kinetics. Conclusions: These data support the use of population-based measures of C-peptide kinetics to estimate β-cell function during an OGTT.