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

3 years ago

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

Adrian Vella, Francesca Piccinini, Marcello C. Laurenti, Chiara Dalla Man, Anu Sharma, Robert A. Rizza, Meera Shah, Ron T. Varghese, Kent R. Bailey, Claudio Cobelli

Aims Standardized, population-based kinetics of C-peptide distribution and clearance are used to estimate insulin secretion from plasma C-peptide concentrations without direct measurement of C-peptide kinetics. We then compared the performance of population-based kinetics to directly measured C-peptide kinetics when used to calculate β-cell responsivity indices. To ensure that population-based kinetics apply to all conditions where β-cell function is measured, subjects were studied in the presence and absence of acute insulin resistance. Materials and Methods Somatostatin was used to inhibit endogenous insulin secretion in 56 nondiabetic subjects. Subsequently, a C-peptide bolus was administered and the changing concentrations used to calculate individual kinetic parameters of C-peptide clearance. In addition, they were studied on 2 occasions in random order using an oral glucose tolerance test (OGTT). On one occasion, free fatty acid (FFA) elevation to cause insulin resistance, was achieved by infusion of intralipid + heparin. 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 parameters (k12 and k21) of the model describing C-peptide kinetics, but smaller differences in the fractional clearance, i.e. the irreversible loss from the accessible compartment (k01), obtained from population-based estimates compared to experimental measurement. Since it is predominantly influenced by k01, DI estimated using individual kinetics correlated well with those 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 OGTT.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/dom.13106