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Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients
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OBJECTIVE—To quantitate the separate impact of obesity and hyperlycemia on the incretin effect (i.e., the gain in β-cell function after oral glucose versus intravenous glucose). RESEARCH DESIGN AND METHODS—Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51 subjects (24 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT], and 10 with type 2 diabetes) with a wide range of BMI (20–61 kg/m2). C-peptide deconvolution was used to reconstruct insulin secretion rates, and β-cell glucose sensitivity (slope of the insulin secretion/glucose concentration dose-response curve) was determined by mathematical modeling. The incretin effect was defined as the oral-to-intravenous ratio of responses. In 8 subjects with NGT and 10 with diabetes, oral glucose appearance was measured by the double-tracer technique. RESULTS—The incretin effect on total insulin secretion and β-cell glucose sensitivity and the GLP-1 response to oral glucose were significantly reduced in diabetes compared with NGT or IGT (P ≤ 0.05). The results were similar when subjects were stratified by BMI tertile (P ≤ 0.05). In the whole dataset, each manifestation of the incretin effect was inversely related to both glucose tolerance (2-h plasma glucose levels) and BMI (partial r = 0.27–0.59, P ≤ 0.05) in an independent, additive manner. Oral glucose appearance did not differ between diabetes and NGT and was positively related to the GLP-1 response (r = 0.53, P < 0.01). Glucagon suppression during the oral glucose tolerance test was blunted in diabetic patients. CONCLUSIONS—Potentiation of insulin secretion, glucose sensing, glucagon-like peptide-1 release, and glucagon suppression are physiological manifestations of the incretin effect. Glucose tolerance and obesity impair the incretin effect independently of one another.
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“Also, we only tested young and healthy adults and did not confirm our results in obese subjects or patients with impaired glucose metabolism (18, 37).”
From Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods (2023) · cites this paper as [37]
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Metadata
- Authors
- Muscelli, E., Mari, A., Casolaro, A., Camastra, S., Seghieri, G., Gastaldelli, A., Holst, J. J., & Ferrannini, E.
- Affiliations
- University of Pisa (IT)
- National Research Council (IT)
- Division of Internal Medicine, Spedali Riuniti, Pistoia, Italy
- University of Copenhagen (DK)
- Corresponding author
- Ferrannini, Ele
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-05-01
- Volume
- 57
- Issue
- 5
- Pages
- 1340-1348
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2145818242
- Cited by
- 409
- References
- 50
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 17 · 2023: 19 · 2022: 23 · 2021: 21 · 2020: 17 · 2019: 22 · 2018: 20 · 2017: 27 · 2016: 22 · 2015: 35 · 2014: 35 · 2013: 34 · 2012: 20
- FWCI
- 18.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- incretin effect, obesity, glucose tolerance, type 2 diabetes, impaired glucose tolerance, beta-cell function, beta-cell glucose sensitivity, glucagon-like peptide-1, glucagon suppression, insulin secretion, body mass index, hyperglycemia
- MeSH terms
- Insulin Secretion, Adult, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Obesity, Reference Values, Body Mass Index, Insulin-Secreting Cells
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