β-Cell function during insulin-modified intravenous glucose tolerance test successfully assessed by the C-peptide minimal model
Abstract
The insulin-modified intravenous glucose tolerance test (IM-IVGTT) is increasingly used to measure insulin sensitivity. However, the assessment of beta-cell secretion is usually made using rough indices. The aim here is to evaluate the ability of the minimal model of C-peptide secretion and kinetics recently proposed for the standard IVGTT (S-IVGTT) to also assess beta-cell function during the IM-IVGTT. C-peptide and glucose data from the IM-IVGTT in 15 normal humans were analyzed. The results show that the same rich beta-cell picture from the S-IVGTT can be obtained during an IM-IVGTT. In particular, in each individual, the time course of beta-cell secretion can be reconstructed and the functional indices of glucose control on first-phase (phi1), second-phase (phi2), and basal (phi(b)) insulin secretion can be estimated (phi1 = 191 +/- 29, phi2 = 10.9 +/- 1.4 x 10(-9) x min(-1), and phi(b) = 5.7 +/- 1.0 x 10(-9) x min(-1), mean +/- SE). Finally, the comparison between IM-IVGTT and S-IVGTT phi1, phi2, and phi(b) values suggest they are not affected by insulin administration.
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Using an insulin-modified FSIGT instead of an OGTT limited confounding from gastrointestinal or incretin effects, and together with a minimal-model approach allowed more precise quantification of specific components of glucose metabolism (SI, β-cell function, glucose effectiveness, and hepatic extraction).
“Unlike previous studies that relied on OGTT, we used the insulin-modified FSIGT to limit confounding from gastrointestinal or incretin effects. Together with a minimal-model approach, this allowed more precise quantification of specific components of glucose metabolism, such as SI, β-cell function, glucose effectiveness, and hepatic extraction (15–17).”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [16]
Measures of insulin secretion, including β-cell responsivity indices and the minute-by-minute insulin secretory rate, were estimated using FSIGT C-peptide models based on plasma glucose and C-peptide.
“Measures of insulin secretion, including a set of β-cell responsivity indices (Φ) and the minute-by-minute insulin secretory rate (ISR), were estimated using FSIGT C-peptide models (16), based on plasma concentrations of glucose and C-peptide.”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [16]
The two prior human in vivo studies did not observe differences in insulin responses, but their measures (acute insulin response to glucose or AUC) relied on circulating insulin concentrations and did not take into account hepatic insulin extraction, whole-body insulin clearance, and prevailing glucose levels, and thus did not independently determine β-cell function.
“Neither of the aforementioned human in vivo studies observed differences in insulin responses (9,10). However, the measures of those two studies (acute insulin response to glucose or AUC) relied on circulating insulin concentrations and did not take into account hepatic insulin extraction, whole-body insulin clearance, and prevailing glucose levels and, thus, did not independently determine β-cell”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [16]
Cites
Quantitative estimation of insulin sensitivity.
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Mechanisms of the Age-Associated Deterioration in Glucose Tolerance
Basu, R., Breda, E., Oberg, A. L., Powell, C. C., Dalla Man, C., Basu, A., Vittone, J. L., Klee, G. G., Arora, P., Jensen, M. D., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1738 · Cited by 440 · see citing works
Self-citationOral Glucose Tolerance Test Minimal Model Indexes of β-Cell Function and Insulin Sensitivity
Breda, E., Cavaghan, M. K., Toffolo, G., Polonsky, K. S., & Cobelli, C. (2001) · Diabetes · doi:10.2337/diabetes.50.1.150 · Cited by 320 · see citing works
Self-citationBock, G., Dalla Man, C., Campioni, M., Chittilapilly, E., Basu, R., Toffolo, G., Cobelli, C., & Rizza, R. (2006) · Diabetes · doi:10.2337/db06-0319 · Cited by 230 · see citing works
Self-citationToffolo, G., Breda, E., Cavaghan, M. K., Ehrmann, D. A., Polonsky, K. S., & Cobelli, C. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.1.e2 · Cited by 112 · see citing works
Self-citationBasu, R., Dalla Man, C., Campioni, M., Basu, A., Nair, K. S., Jensen, M. D., Khosla, S., Klee, G., Toffolo, G., Cobelli, C., et al. (2007) · Diabetes · doi:10.2337/db06-1504 · Cited by 63 · see citing works
Self-citationQian, J., Stefanovski, D., Andersen, P. A. K., Vujovic, N., Kelly, L., Lepson, J., Nguyen, H., Byrne, S., Wang, W., Mandrup-Poulsen, T., et al. (2026) · Diabetes Care · doi:10.2337/dc26-0164
- Authors
- Toffolo, G., Cefalu, W. T., & Cobelli, C.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Cobelli, Claudio
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 48
- Issue
- 9
- Pages
- 1162-1166
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2169171744
- Cited by
- 37
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- beta-cell function, first-phase insulin secretion, second-phase insulin secretion, basal insulin secretion, insulin sensitivity, glucose tolerance test, insulin administration
- MeSH terms
- C-Peptide, Glucose Tolerance Test, Humans, Insulin, Islets of Langerhans, Kinetics, Middle Aged, Sensitivity and Specificity
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