Oral Glucose Tolerance Test Minimal Model Indexes of β-Cell Function and Insulin Sensitivity
Open accessAbstract
The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies—the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT300-22) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose (Φs [109 min-1] and Φd [109]) and the insulin sensitivity index (SI) (105 dl/kg per min per pmol/l) were estimated by using the minimal model of C-peptide secretion and kinetics originally proposed for intravenous graded glucose infusion and the minimal model approach recently proposed for meal/OGTTs. The indexes obtained from FSOGTT300-22 were used as a reference for internal validation of OGTT protocols with reduced sampling schedules. Our results show that 11 samples in a 300-min period (OGTT300-11) is the test of choice because the indexes it provides (Φs = 36 ± 3 [means ± SE]; Φd = 710 ± 111; SI = 10.2 ± 2.4) show excellent correlation and are not statistically different from those of FSOGTT300-22 (Φs = 33 ± 3; Φd = 715 ± 120; SI = 10.1 ± 2.3). In conclusion, OGTT300-11, interpreted with C-peptide and glucose minimal models, provides a quantitative description of β-cell function and insulin sensitivity in a single individual while preserving the important clinical classification of glucose tolerance provided by the standard 120-min OGTT.
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The C-peptide minimal model allows exploration of the influence of glucose concentrations on insulin secretion after a glucose perturbation.
“one can use the C-peptide minimal model (4), which allows exploration of the influence of glucose concentrations on insulin secretion, after a glucose perturbation.”
From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [4]
The model describing glucose-dependent insulin secretion is linear in both Φd and Φs; doubling Φd or Φs results in doubling SRd or SRs, respectively.
“the model describing the glucose-dependent insulin secretion (4, 28) is linear in both Φd and Φs; i.e., doubling Φd or Φs results in doubling SRd or SRs, respectively.”
From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [4]
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Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus* (2002) · Diabetes Care · doi:10.2337/diacare.25.2007.s5 · Cited by 10,320 · see citing works
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425 · see citing works
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997) · Diabetes Care · doi:10.2337/diacare.20.7.1183 · Cited by 6,220 · see citing works
Efron, B., & Tibshirani, R. (1986) · Statistical Science · doi:10.1214/ss/1177013815 · Cited by 6,033 · see citing works
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Morgan, C. R., & Lazarow, A. (1963) · Diabetes · doi:10.2337/diab.12.2.115 · Cited by 2,212 · see citing works
Quantitative estimation of insulin sensitivity.
Bergman, R. N., Ider, Y. Z., Bowden, C. R., & Cobelli, C. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.236.6.e667 · Cited by 1,874 · see citing works
Self-citationBergman, R. N., Phillips, L. S., & Cobelli, C. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110398 · Cited by 1,640 · see citing works
Self-citationKahn, S. E., Prigeon, R. L., McCulloch, D. K., Boyko, E. J., Bergman, R. N., Schwartz, M. W., Neifing, J. L., Ward, W. K., Beard, J. C., & Palmer, J. P. (1993) · Diabetes · doi:10.2337/diab.42.11.1663 · Cited by 1,405 · see citing works
Cauter, E. V., Mestrez, F., Sturis, J., & Polonsky, K. (1992) · Diabetes · doi:10.2337/diab.41.3.368 · Cited by 938 · see citing works
Self-citationCauter, E. V., Mestrez, F., Sturis, J., et al. (1992) · Diabetes · doi:10.2337/diabetes.41.3.368 · Cited by 643 · see citing works
Polonsky, K. S., Sturis, J., & Bell, G. I. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341207 · Cited by 590 · see citing works
Self-citationSAAM II: Simulation, analysis, and modeling software for tracer and pharmacokinetic studies
Barrett, P. H. R., Bell, B. M., Cobelli, C., Golde, H., Schumitzky, A., Vicini, P., & Foster, D. M. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90064-6 · Cited by 445 · see citing works
Self-citationPrehepatic Insulin Production in Man: Kinetic Analysis Using Peripheral Connecting Peptide Behavior*
EATON, R. P., ALLEN, R. C., SCHADE, D. S., ERICKSON, K. M., & STANDEFER, J. (1980) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-51-3-520 · Cited by 363 · see citing works
The mathematical modeling of metabolic and endocrine systems
Twizell, E. H. (1984) · Applied Mathematical Modelling · doi:10.1016/0307-904x(84)90183-5 · Cited by 329 · see citing works
Kahn, S. E., Prigeon, R. L., McCulloch, D. K., Boyko, E. J., Bergman, R. N., Schwartz, M. W., Neifing, J. L., Ward, W. K., Beard, J. C., Palmer, J. P., et al. (1993) · Diabetes · doi:10.2337/diabetes.42.11.1663 · Cited by 328 · see citing works
Characterization of Seven C-peptide Antisera
FABER, O. K., Binder, C., Markussen, J., Hedïng, L. G., Naithani, V. K., Kuzuya, H., BLIX, P. M., Horwitz, D. L., & Rubenstein, A. H. (1978) · Diabetes · doi:10.2337/diab.27.1.s170 · Cited by 230 · see citing works
Insulin Sensitivity from Meal Tolerance Tests in Normal Subjects: A Minimal Model Index
Caumo, A., Bergman, R. N., & Cobelli, C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6982 · Cited by 206 · see citing works
Self-citationTOFFOLO, G. M., Grandi, F. D., & Cobelli, C. (1995) · Diabetes · doi:10.2337/diab.44.7.845 · Cited by 134 · 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-citationHovorka, R., Chassin, L. J., Luzio, S. D., Playle, R., & Owens, D. R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.3.4646 · Cited by 90 · see citing works
Basu, A., Caumo, A., Bettini, F., Gelisio, A., Alzaid, A., Cobelli, C., & Rizza, R. A. (1997) · Diabetes · doi:10.2337/diab.46.3.421 · Cited by 86 · see citing works
Self-citationHampton, S. M., Morgan, L. M., Tredger, J. A., Cramb, R., & Marks, V (1986) · Diabetes · doi:10.2337/diab.35.5.612 · Cited by 80 · see citing works
Tracer Kinetics in Biomedical Research
Cobelli, C., Foster, D., & TOFFOLO, G. M. (2002) · Springer eBooks · doi:10.1007/b112199 · Cited by 68 · see citing works
Self-citationIntegrated mathematical model to assess beta-cell activity during the oral glucose test
Thomaseth, K., Kautzky‐Willer, A., Ludvik, B. H., Prager, R., & Pacini, G. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.3.e522 · Cited by 48 · see citing works
Toffolo, G., Cefalu, W. T., & Cobelli, C. (1999) · Metabolism · doi:10.1016/s0026-0495(99)90132-4 · Cited by 37 · see citing works
Self-citationHovorka, R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.3.744 · Cited by 30 · see citing works
Basu, A., Caumo, A., Bettini, F., et al. (1997) · Diabetes · doi:10.2337/diabetes.46.3.421 · Cited by 20 · see citing works
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Meal Simulation Model of the Glucose-Insulin System
Dalla Man, C., Rizza, R. A., & Cobelli, C. (2007) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2007.893506 · Cited by 955 · see citing works
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Leighton, E., Sainsbury, C. A., & Jones, G. C. (2017) · Diabetes Therapy · doi:10.1007/s13300-017-0265-4 · Cited by 773 · see citing works
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Cobelli, C., Dalla Man, C., Sparacino, G., Magni, L., De Nicolao, G., & Kovatchev, B. P. (2009) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2009.2036073 · Cited by 511 · see citing works
Self-citationPalmer, J. P., Fleming, G. A., Greenbaum, C. J., Herold, K. C., Jansa, L. D., Kolb, H., Lachin, J. M., Polonsky, K. S., Pozzilli, P., Skyler, J. S., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.1.250 · Cited by 491 · see citing works
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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
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Petersen, K. F., Dufour, S., Feng, J., Befroy, D., Dziura, J., Man, C. D., Cobelli, C., & Shulman, G. I. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608537103 · Cited by 403 · see citing works
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Basu, R., Dalla Man, C., Campioni, M., Basu, A., Klee, G., Toffolo, G., Cobelli, C., & Rizza, R. A. (2006) · Diabetes · doi:10.2337/db05-1692 · Cited by 334 · see citing works
Self-citationModel Predictive Control of Type 1 Diabetes: An <i>in Silico</i> Trial
Magni, L., Raimondo, D. M., Bossi, L., Dalla Man, C., De Nicolao, G., Kovatchev, B., & Cobelli, C. (2007) · Journal of Diabetes Science and Technology · doi:10.1177/193229680700100603 · Cited by 317 · see citing works
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Mari, A., Schmitz, O., Gastaldelli, A., Oestergaard, T., Nyholm, B., & Ferrannini, E. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00093.2002 · Cited by 303 · see citing works
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Saad, A., Dalla Man, C., Nandy, D. K., Levine, J. A., Bharucha, A. E., Rizza, R. A., Basu, R., Carter, R. E., Cobelli, C., Kudva, Y. C., et al. (2012) · Diabetes · doi:10.2337/db11-1478 · Cited by 297 · see citing works
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Pepino, M. Y., Tiemann, C. D., Patterson, B. W., Wice, B. M., & Klein, S. (2013) · Diabetes Care · doi:10.2337/dc12-2221 · Cited by 253 · see citing works
Hebert, M., Ma, X., Naraharisetti, S., Krudys, K., Umans, J., Hankins, G., Caritis, S., Miodovnik, M., Mattison, D., Unadkat, J., et al. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.5 · Cited by 252 · 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
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Dalla Man, C., Campioni, M., Polonsky, K. S., Basu, R., Rizza, R. A., Toffolo, G., & Cobelli, C. (2005) · Diabetes · doi:10.2337/diabetes.54.11.3265 · Cited by 179 · see citing works
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Self-citationCali, A. M. G., Man, C. D., Cobelli, C., Dziura, J., Seyal, A., Shaw, M., Allen, K., Chen, S., & Caprio, S. (2009) · Diabetes Care · doi:10.2337/dc08-1274 · Cited by 125 · see citing works
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Jastreboff, A. M., Lacadie, C., Seo, D., Kubat, J., Van Name, M. A., Giannini, C., Savoye, M., Constable, R. T., Sherwin, R. S., Caprio, S., et al. (2014) · Diabetes Care · doi:10.2337/dc14-0525 · Cited by 83 · see citing works
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Self-citationCampioni, M., Toffolo, G., Shuster, L. T., Service, F. J., Rizza, R. A., & Cobelli, C. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00033.2006 · Cited by 40 · see citing works
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Self-citation
- Authors
- Breda, E., Cavaghan, M. K., Toffolo, G., Polonsky, K. S., & Cobelli, C.
- Affiliations
- University of Padua (IT)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-01-01
- Volume
- 50
- Issue
- 1
- Pages
- 150-158
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2132549450
- Cited by
- 320
- References
- 29
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 11 · 2020: 14 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 18 · 2015: 18 · 2014: 18 · 2013: 21 · 2012: 16
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- University of Chicago
- National Institutes of Health (1k23dk002742-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-31842, DK 20595, DK-02742)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- oral glucose tolerance test, minimal models, beta-cell function, insulin sensitivity, C-peptide secretion, insulin secretion, glucose tolerance, sampling schedule
- MeSH terms
- Adult, Blood Glucose, C-Peptide, Female, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Islets of Langerhans, Male, Models, Biological, Specimen Handling
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