Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 549-555 |
| Number of pages | 7 |
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2018 |
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Keywords
- acute insulin resistance
- C-peptide fractional clearance
- hepatic insulin extraction
- insulin action
- insulin secretion
- β-cell function
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology
Cite this
Performance of individually measured vs population-based C-peptide kinetics to assess β-cell function in the presence and absence of acute insulin resistance. / Varghese, Ron T.; Dalla Man, Chiara; Laurenti, Marcello C.; Piccinini, Francesca; Sharma, Anu; Shah, Meera; Bailey, Kent R; Rizza, Robert A.; Cobelli, Claudio; Vella, Adrian.
In: Diabetes, Obesity and Metabolism, Vol. 20, No. 3, 01.03.2018, p. 549-555.Research output: Contribution to journal › Article
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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
PY - 2018/3/1
Y1 - 2018/3/1
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 - acute insulin resistance
KW - C-peptide fractional clearance
KW - hepatic insulin extraction
KW - insulin action
KW - insulin secretion
KW - β-cell function
UR - http://www.scopus.com/inward/record.url?scp=85042100435&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042100435&partnerID=8YFLogxK
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 -