Insulin Resistance Is Accompanied by Increased Fasting Glucagon and Delayed Glucagon Suppression in Individuals With Normal and Impaired Glucose Regulation
Abstract
Hyperinsulinemia is an adaptive mechanism that enables the maintenance of normoglycemia in the presence of insulin resistance. We assessed whether glucagon is also involved in the adaptation to insulin resistance. A total of 1,437 individuals underwent an oral glucose tolerance test with measurements of circulating glucose, insulin, and glucagon concentrations at 0, 30 and 120 min. Early glucagon suppression was defined as suppression in the period from 0 to 30 min, and late glucagon suppression as 30 to 120 min after glucose intake. Insulin sensitivity was estimated by the validated insulin sensitivity index. Individuals with screen-detected diabetes had 30% higher fasting glucagon levels and diminished early glucagon suppression, but greater late glucagon suppression when compared with individuals with normal glucose tolerance (P ≤ 0.014). Higher insulin resistance was associated with higher fasting glucagon levels, less early glucagon suppression, and greater late glucagon suppression (P < 0.001). The relationship between insulin sensitivity and fasting glucagon concentrations was nonlinear (P < 0.001). In conclusion, increased fasting glucagon levels and delayed glucagon suppression, together with increased circulating insulin levels, develop in parallel with insulin resistance. Therefore, glucose maintenance during insulin resistance may depend not only on hyperinsulinemia but also on the ability to suppress glucagon early after glucose intake.
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Increased fasting glucagon and delayed glucagon suppression go along with insulin resistance in individuals with normal and impaired glucose regulation.
“increased fasting glucagon and delayed glucagon suppression have been shown to go along with insulin resistance in individuals with normal and impaired glucose regulation (10)”
From Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test (2021) · cites this paper as [10]
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“Moreover, increased fasting glucagon and delayed glucagon suppression have been shown to go along with insulin resistance in individuals with normal and impaired glucose regulation (10).”
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- Authors
- Færch, K., Vistisen, D., Pacini, G., Torekov, S. S., Johansen, N. B., Witte, D. R., Jonsson, A., Pedersen, O., Hansen, T., Lauritzen, T., Jørgensen, M. E., Ahrén, B., & Holst, J. J.
- Affiliations
- Steno Diabetes Center, Gentofte, Denmark
- National Research Council (IT)
- University of Copenhagen (DK)
- Danish Diabetes Academy (DK)
- Aarhus University (DK)
- Division of Medicine, Lund University, Lund, Sweden
- Corresponding author
- Færch, Kristine
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2016-08-08
- Volume
- 65
- Issue
- 11
- Pages
- 3473-3481
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2482901886
- Cited by
- 217
- References
- 37
- Citations by year
- 2026: 19 · 2025: 21 · 2024: 40 · 2023: 19 · 2022: 24 · 2021: 28 · 2020: 19 · 2019: 20 · 2018: 14 · 2017: 9 · 2016: 3
- FWCI
- 16.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Health Services in the counties of Copenhagen, Aarhus, Ringkøbing, Ribe, and Southern Jutland in Denmark
- Danish Council for Strategic Research;
- Danish Research Foundation for General Practice
- Danish Centre for Evaluation and Health Technology Assessment
- Diabetes Fund of the National Board of Health
- Danish Medical Research Council
- Aarhus University Research Foundation
- European Foundation for the Study of Diabetes/Pfizer for Research into Cardiovascular Disease Risk Reduction in Patients with Diabetes (74550801)
- Novo Nordisk Foundation
- 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 Treatment and Management
- Keywords
- insulin resistance, glucagon, glucagon suppression, hyperinsulinemia, prediabetes, insulin sensitivity, glucose tolerance, oral glucose tolerance test, screen-detected diabetes, glucose homeostasis
- MeSH terms
- Aged, Blood Glucose, Diabetes Mellitus, Type 2, Fasting, Female, Glucagon, Glucose, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Prediabetic State, Cohort Studies
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