Integrated model of hepatic and peripheral glucose regulation for estimation of endogenous glucose production during the hot IVGTT
Abstract
We have developed a new model to describe endogenous glucose kinetics during a labeled (hot) intravenous glucose tolerance test (IVGTT) to derive a time profile of endogenous glucose production (EGP). We reanalyzed data from a previously published study (P. Vicini, J. J. Zachwieja, K. E. Yarasheski, D. M. Bier, A. Caumo, and C. Cobelli. Am J Physiol Endocrinol Metab 276: E285–E294, 1999), in which insulin-modified [6,6-2 H 2]glucose-labeled IVGTTs (0.33 g/kg glucose) were performed in 10 normal subjects. In addition, a second tracer ([U-13 C]glucose) was infused in a variable rate to clamp the endogenous glucose tracer-to-tracee ratio (TTR). Our new model describing endogenous glucose kinetics was incorporated into the two-compartment hot minimal-model structure. The model gave estimates of glucose effectiveness [1.54 ± 0.31 (SE) ml·kg−1·min−1], insulin sensitivity (37.74 ± 5.23 10 4 dl·kg−1·min−1·μU−1·ml), and a new parameter describing the sensitivity of EGP to the inhibitory effect of insulin (IC 50 = 0.0195 ± 0.0046 min−1). The model additionally provided an estimate of the time course of EGP showing almost immediate inhibition, followed by a secondary inhibitory effect caused by infusion of insulin, and a large overshoot as EGP returns to its basal value. Our estimates show very good agreement with those obtained via deconvolution and the model-independent TTR clamp technique. These results suggest that the new integrated model can serve as a simple one-step approach to obtain metabolic indexes while also providing a parametric description of EGP.
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Most existing mathematical models of postprandial endogenous glucose production suppression use plasma glucose and not endogenous glucose production as the variable to fit.
“However, most of them use plasma glucose and not EGP as a variable to fit.”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [10]
Some mathematical models exist in the literature describing postprandial endogenous glucose production suppression as a function of plasma glucose, insulin, and glucagon.
“Some mathematical models exist in the literature describing the postprandial EGP suppression as a function of plasma glucose, insulin [10, 11], and glucagon [12–15].”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [10]
In these experimental conditions, this model and the other models of the literature are still suboptimal because they do not account for the glucagon evanescent effect visible in the data.
“Nonetheless, in our experimental conditions, this [11] and the other models of the literature [10, 12–15] are still suboptimal since they do not account for the glucagon evanescent effect visible in the data (Fig. 1, Panel D).”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [10]
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- Authors
- Krudys, K. M., Dodds, M. G., Nissen, S. M., & Vicini, P.
- Affiliations
- University of Washington (US)
- ORCID
- Dodds, Michael G.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2005-05
- Volume
- 288
- Issue
- 5
- Pages
- E1038-E1046
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2131473533
- Cited by
- 30
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 1 · 2013: 1 · 2012: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (P41EB001975)
- National Institute of Dental and Craniofacial Research (T32 DE07023, T32DE007023)
- 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
- endogenous glucose production, glucose kinetics, minimal models, glucose effectiveness, insulin sensitivity, [U-13C]glucose, deconvolution
- MeSH terms
- Blood Glucose, Computer Simulation, Diagnosis, Computer-Assisted, Glucose, Glucose Tolerance Test, Humans, Insulin Resistance, Kinetics, Liver, Metabolic Clearance Rate, Models, Biological, Radioisotope Dilution Technique, Sensitivity and Specificity, Reproducibility of Results
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