4.7 Article

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

Journal

DIABETES OBESITY & METABOLISM
Volume 20, Issue 3, Pages 549-555

Publisher

WILEY
DOI: 10.1111/dom.13106

Keywords

acute insulin resistance; C-peptide fractional clearance; hepatic insulin extraction; insulin action; insulin secretion; -cell function

Funding

  1. National Institutes of Health [UL1 TR000135, R01 DK78646, 5T32 DK007352-37]

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AimsTo compare the performance of population-based kinetics with that of directly measured C-peptide kinetics when used to calculate -cell responsivity indices, and to study people with and without acute insulin resistance to ensure that population-based kinetics apply to all conditions where -cell function is measured. MethodsSomatostatin 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. ResultsThere were marked differences in the exchange variables (k(12) and k(21)) of the model describing C-peptide kinetics, but smaller differences in the fractional clearance; that is, the irreversible loss from the accessible compartment (k(01)), obtained from population-based estimates compared with experimental measurement. Because it is predominantly influenced by k(01), DI estimated using individual kinetics correlated well with DI estimated using population-based kinetics. ConclusionsThese data support the use of population-based measures of C-peptide kinetics to estimate -cell function during an OGTT.

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