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Cited by 303Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes Management and Research

Meal and oral glucose tests for assessment of β-cell function: modeling analysis in normal subjects

Mari, Andrea, Schmitz, Ole, Gastaldelli, Amalia, Oestergaard, Torben, Nyholm, Birgit, Ferrannini, Ele·2002·American Journal of Physiology-Endocrinology and Metabolism
DOI 10.1152/ajpendo.00093.2002
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Abstract

We investigated β-cell function and its relationship to insulin sensitivity in 17 normal volunteers. For insulin secretion (derived by C-peptide deconvolution), a mathematical model was applied to 24-h triple-meal tests (MT) as well as oral glucose tolerance tests (OGTT); insulin sensitivity was assessed by the euglycemic insulin clamp technique. The β-cell model featured a glucose concentration-insulin secretion dose response (characterized by secretion at 5 mM glucose and slope), a secretion component proportional to the glucose concentration derivative, and a time-dependent potentiation factor (modulating the dose response and accounting for effects of sustained hyperglycemia and incretins). The β-cell dose-response functions estimated from the whole 24-h MT, the first 2 h of the MT, and the OGTT differed systematically, because a different potentiation factor was involved. In fact, potentiation was higher than average during meals (1.6 ± 0.1-fold during the first meal) and had a different time course in the MT and OGTT. However, if potentiation was accounted for, the 24- and 2-h MT and the OGTT yielded similar dose responses, and most β-cell function parameters were intercorrelated ( r = 0.50–0.86, P ≤ 0.05). The potentiation factor was found to be related to plasma glucose-dependent insulin-releasing polypeptide concentrations ( r = 0.49, P< 0.0001). Among β-cell function parameters, only insulin secretion at 5 mM glucose from MT correlated inversely with insulin sensitivity (24-h MT: r = −0.74, P < 0.001; 2-h MT: r = −0.52, P < 0.05), whereas the dose-response slope and the OGTT parameters did not. In nine other subjects, reproducibility of model parameters was evaluated from repeated MTs. Coefficients of variation were generally ∼20%, but the derivative component was less reproducible. We conclude that our model for the multiple MT yields useful information on β-cell function, particularly with regard to the role of potentiation. With cautious interpretation, a 2-h MT or a standard OGTT can be used as surrogates of 24-h tests in assessing spontaneous β-cell function.

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  • The only model that indirectly accounts for a potentiation due to incretin is the one proposed by Mari et al.

    “The only model that indirectly accounts for a potentiation due to incretin is the one proposed by Mari et al. (20).”

    From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [20]

  • The Mari et al. model introduced a potentiating factor that modulates the dose-response relation between insulin secretion and plasma glucose to better fit C-peptide data, but did not explicitly describe the incretin effect.

    “It introduced a potentiating factor, which modulates the dose-response relation between insulin secretion and plasma glucose to better fit the C-peptide data, but it did not explicitly describe the incretin effect.”

    From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [20]

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Authors
Mari, A., Schmitz, O., Gastaldelli, A., Oestergaard, T., Nyholm, B., & Ferrannini, E.
Affiliations
  • National Research Council (IT)
  • Aarhus University Hospital (DK)
  • University of Pisa (IT)
  • Department of Medicine M (Endocrinology and Diabetes), University Hospital, DK-8000 Aarhus, Denmark
ORCID
Venue
American Journal of Physiology-Endocrinology and Metabolism
Publisher
American Physiological Society
Published
2002-12-01
Volume
283
Issue
6
Pages
E1159-E1166
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
DOI
10.1152/ajpendo.00093.2002
OpenAlex
W1998802885
Cited by
303
References
14
Citations by year
2026: 6 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 13 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 19 · 2017: 18 · 2016: 17 · 2015: 21 · 2014: 20 · 2013: 17 · 2012: 14
FWCI
7.27
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
beta-cell function, insulin secretion, oral glucose tolerance test, insulin sensitivity, hyperinsulinemic-euglycemic clamp, mathematical modeling, reproducibility
MeSH terms
Insulin Secretion, Adult, Blood Glucose, C-Peptide, Dose-Response Relationship, Drug, Female, Food, Formulated, Gastric Inhibitory Polypeptide, Glucose, Glucose Tolerance Test, Humans, Insulin, Islets of Langerhans, Male, Reference Values, Reproducibility of Results, Glucose Clamp Technique

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