Advancing Our Understanding of the Glucose System via Modeling: A Perspective
Abstract
The glucose story begins with Claude Bernard's discovery of glycogen and milieu interieur, continued with Banting's and Best's discovery of insulin and with Rudolf Schoenheimer's paradigm of dynamic body constituents. Tracers and compartmental models allowed moving to the first quantitative pictures of the system and stimulated important developments in terms of modeling methodology. Three classes of multiscale models, models to measure, models to simulate, and models to control the glucose system, are reviewed in their historical development with an eye to the future.
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Several models have re-examined physiological and clinical data from a dynamical perspective to shed light on mechanisms leading to diabetes, with uncompensated insulin resistance at their core.
“several models ( 17-19 ) have re-examined physiological and clinical data from a dynamical perspective to shed light on the mechanisms leading to diabetes, with uncompensated insulin resistance at their core ( 20, 21 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [18]
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Self-citationMirouze, J., Selam, J. L., Pham, T. C., & Cavadore, D. (1977) · Diabetologia · doi:10.1007/bf01219712 · Cited by 86 · see citing works
Cobelli, C., & Ruggeri, A. (1983) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.1983.325203 · Cited by 82 · see citing works
Self-citationModular Artificial β-Cell System: A Prototype for Clinical Research
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Introduction to Modeling in Physiology and Medicine
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The Theory of the Study of Transfers within a Multi-Compartment System Using Isotopic Tracers
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Comparison of Algorithms for the Closed-Loop Control of Blood Glucose Using the Artificial Beta Cell
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Man, C. D., Caumo, A., Basu, R., Rizza, R. A., TOFFOLO, G. M., & Cobelli, C. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00299.2004 · Cited by 59 · see citing works
Self-citationControl of Blood Glucose in Diabetics using an Artificial Pancreas*
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A subcellular model of glucose-stimulated pancreatic insulin secretion
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Self-citationBertoldo, A., Pencek, R. R., Azuma, K., Price, J. C., Kelley, C., Cobelli, C., & Kelley, D. E. (2006) · Diabetes · doi:10.2337/db06-0762 · Cited by 52 · see citing works
Self-citationSonntag, A., Pezze, P. D., Shanley, D. P., & Thedieck, K. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08582.x · Cited by 50 · see citing works
Assessment of postprandial glucose metabolism: conventional dual- vs. triple-tracer method
TOFFOLO, G. M., Basu, R., Man, C. D., Rizza, R. A., & Cobelli, C. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00461.2005 · Cited by 50 · see citing works
Self-citationA model of GLP-1 action on insulin secretion in nondiabetic subjects
Dalla Man, C., Micheletto, F., Sathananthan, A., Rizza, R. A., Vella, A., & Cobelli, C. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00705.2009 · Cited by 45 · see citing works
Self-citationA compartmental model to quantitate in vivo glucose transport in the human forearm
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Self-citationCalculation of the Systemic Delivery Rate of Insulin in Normal Man*
Polonsky, K. S., Given, B. D., PUGH, W., Licinio, J., THOMPSON, J. E., Karrison, T. G., & Rubenstein, A. H. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-1-113 · Cited by 43 · see citing works
Studies in the concentration of indifferent narcotics in blood and tissues
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Cellular modeling: insight into oral minimal models of insulin secretion
Pedersen, M. G., TOFFOLO, G. M., & Cobelli, C. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00670.2009 · Cited by 41 · see citing works
Self-citationWilliams, K. V., Bertoldo, A., Kinahan, P. E., Cobelli, C., & Kelley, D. E. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1619 · Cited by 33 · see citing works
Self-citationTOFFOLO, G. M., Grandi, F. D., & Cobelli, C. (1995) · Diabetes · doi:10.2337/diabetes.44.7.845 · Cited by 30 · see citing works
Self-citationArtom, C., Sarzana, G., & Segrè, E. G. (1938) · Archives Internationales de Physiologie · doi:10.3109/13813453809148721 · Cited by 30 · see citing works
Norwich, K. H., Radziuk, J., Lau, D., & Vranić, M. (1974) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y74-068 · Cited by 28 · see citing works
Ličko, V., & Silvers, A. (1975) · Mathematical Biosciences · doi:10.1016/0025-5564(75)90110-8 · Cited by 27 · see citing works
Man, C. D., Piccinini, F., Basu, R., Basu, A., Rizza, R. A., & Cobelli, C. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00482.2012 · Cited by 26 · see citing works
Self-citationThe disposition index: from individual to population approach
Denti, P., TOFFOLO, G. M., & Cobelli, C. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00139.2011 · Cited by 25 · see citing works
Self-citationComparison of models of insulin release
Landahl, H. D., & Grodsky, G. M. (1982) · Bulletin of Mathematical Biology · doi:10.1016/s0092-8240(82)80019-0 · Cited by 23 · see citing works
Multiscale Modeling of Insulin Secretion
Pedersen, M. G., Man, C. D., & Cobelli, C. (2011) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2011.2164918 · Cited by 23 · see citing works
Self-citationA New Dynamic Index of Insulin Sensitivity
Pillonetto, G., Caumo, A., Sparacino, G., & Cobelli, C. (2006) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2005.869654 · Cited by 23 · see citing works
Self-citationGlycemic Control with Closed-Loop Intraperitoneal Insulin in Type I Diabetes
Leblanc, H., Chauvet, D., Lombrail, P., & Robert, J. J. (1986) · Diabetes Care · doi:10.2337/diacare.9.2.124 · Cited by 23 · see citing works
IVGTT glucose minimal model covariate selection by nonlinear mixed-effects approach
Denti, P., Bertoldo, A., Vicini, P., & Cobelli, C. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00656.2009 · Cited by 22 · see citing works
Self-citationUse of labeled oral minimal model to measure hepatic insulin sensitivity
Man, C. D., Toffolo, G., Basu, R., Rizza, R. A., & Cobelli, C. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00486.2007 · Cited by 22 · see citing works
Self-citationGlucose Fluxes During OGTT in Adolescents Assessed by a Stable Isotope Triple Tracer Method
Toffolo, G., Dalla Man, C., Cobelli, C., & Sunehag, A. L. (2008) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2008.21.1.31 · Cited by 22 · see citing works
Self-citationAn Electrical Analog for Analysis of Compartmental Biological Systems
Brownell, G. L., Cavicchi, R. V., & Perry, K. E. (1953) · Review of Scientific Instruments · doi:10.1063/1.1770820 · Cited by 21 · see citing works
Short Term Glucose Homeostasis in Man: A Systems Dynamics Model
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Phenotype forecasting with SNPs data through gene-based Bayesian networks
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Models for the insulin response to intravenous glucose
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A HYDRODYNAMIC MODEL OF ISOTOPE DISTRIBUTION IN LIVING ORGANISMS
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Multiscale modelling of insulin secretion during an intravenous glucose tolerance test
Pedersen, M. G., & Cobelli, C. (2013) · Interface Focus · doi:10.1098/rsfs.2012.0085 · Cited by 11 · see citing works
Self-citation
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1 of the 145 references couldn’t be matched to a known paper.
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In silico clinical trials: how computer simulation will transform the biomedical industry
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Glucose Variability: Timing, Risk Analysis, and Relationship to Hypoglycemia in Diabetes
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Self-citationVettoretti, M., Facchinetti, A., Sparacino, G., & Cobelli, C. (2017) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2017.2746340 · Cited by 110 · see citing works
Self-citationA Long-Term Model of the Glucose–Insulin Dynamics of Type 1 Diabetes
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Physiological Closed-Loop Control (PCLC) Systems: Review of a Modern Frontier in Automation
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Impulsive Zone MPC for Type I Diabetic Patients based on a long-term model
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A Variable Reference Trajectory for Model-Free Glycemia Regulation
MohammadRidha, T., Moog, C. H., Delaleau, E., Fliess, M., & Join, C. (2015) · Society for Industrial and Applied Mathematics eBooks · doi:10.1137/1.9781611974072.9 · Cited by 24 · see citing works
Clinical impact of blood glucose monitoring accuracy: an in-silico study
Campos-Náñez, E., Fortwaengler, K., & Breton, M. D. (2017) · Journal of Diabetes Science and Technology · doi:10.1177/1932296817710474 · Cited by 22 · see citing works
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Self-citationYet Another Glucose Variability Index: Time for a Paradigm Change?
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A nonlinear time-delay realization for gastroparesis in patients with diabetes
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A differential simulator using past clinical trial data to run simulated clinical trials
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A phenomenological-based semi-physical model of the kidneys and its role in glucose metabolism
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Physiological models for artificial pancreas development
VISENTIN, R., Schiavon, M., Basu, R., Basu, A., Man, C. D., & Cobelli, C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815655-1.00015-6 · Cited by 7 · see citing works
Self-citationPerformance Requirements for Glucose Assays in Intensive Care Units
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A closed-loop microneedle-integrated physiological model for predictive glycemic management
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Prediabetes detection in unconstrained conditions using wearable sensors
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Diabetic Gastroparesis Modeling and Observer Design
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An OGI model for personalized estimation of glucose and insulin concentration in plasma
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Self-citationAlgorithm for Predicting the Glicemic Profil in Diabetes Under Regular Measurements
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Modeling the SMBG measurement error
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Computational modeling of the pancreas and pancreatic function
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- Authors
- Cobelli, C., Dalla Man, C., Pedersen, M. G., Bertoldo, A., & Toffolo, G.
- Affiliations
- University of Padua (IT)
- Venue
- IEEE Transactions on Biomedical Engineering
- Published
- 2014-05
- Volume
- 61
- Issue
- 5
- Pages
- 1577-1592
- ISSN
- 0018-9294 (ISSN-L)
- 1558-2531
- OpenAlex
- W2048014456
- Cited by
- 46
- References
- 145
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- IEEE Transactions on Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- FP7 EU Project AP@home, Italian Ministero dell¿Univerisità e della Ricerca project FIRB 2008, Juvenile Diabetes Research Foundation Simulation Core Facility Grant
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Social Sciences › Arts and Humanities › History and Philosophy of Science › History of Science and Medicine
- Keywords
- glucose homeostasis, compartmental model, tracer kinetics, multiscale modeling, insulin, glycogen, milieu intérieur, glucose regulation
- MeSH terms
- Blood Glucose, Computer Simulation, Diabetes Mellitus, Humans, Insulin, Models, Biological, Organ Specificity, Pancreas, Artificial, Biomedical Research, History, 19th Century, History, 20th Century, History, 21st Century
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