TY - JOUR
T1 - Performance of individually measured vs population-based C-peptide kinetics to assess β-cell function in the presence and absence of acute insulin resistance
AU - Varghese, Ron T.
AU - Dalla Man, Chiara
AU - Laurenti, Marcello C.
AU - Piccinini, Francesca
AU - Sharma, Anu
AU - Shah, Meera
AU - Bailey, Kent R.
AU - Rizza, Robert A.
AU - Cobelli, Claudio
AU - Vella, Adrian
N1 - Funding Information:
This work was supported by the National Institutes of Health grant numbers UL1 TR000135, R01 DK78646, and 5T32 DK007352-37.
Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - C-peptide fractional clearance
KW - acute insulin resistance
KW - hepatic insulin extraction
KW - insulin action
KW - insulin secretion
KW - β-cell function
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U2 - 10.1111/dom.13106
DO - 10.1111/dom.13106
M3 - Article
C2 - 28862812
AN - SCOPUS:85042100435
VL - 20
SP - 549
EP - 555
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 3
ER -