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Cited by 67Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and Lipoproteins

Glucocorticoid induced insulin resistance impairs basal but not glucose entrained high-frequency insulin pulsatility in humans

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Hollingdal, M., Juhl, C. B., Dall, R., Sturis, J., Veldhuis, J. D., Schmitz, O., Pørksen, N.·2002·Diabetologia
DOI 10.1007/s125-002-8244-y
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Abstract

Aims/hypothesis Type II (non-insulin-dependent) diabetes mellitus is characterized by abnormal insulin secretion, which involves a disrupted basal and glucose-entrained insulin pulsatility, and by insulin resistance. The aim of this study was to examine the influence of glucocorticoid-mediated insulin resistance on the regularity of high frequency insulin pulsatility.Methods Eight healthy men (means +/- SD; age 24.4 +/- 0.5 years, BMI 23.2 +/- 0.7 kg/m2) were examined after prednisolone treatment (30 mg/day) or placebo for 6 days in a double-blind, placebo controlled, cross-over study with a 6-week washout period. Blood was collected every minute for 60 min during baseline and glucose-entrainment. Time-series were assessed by spectral and autocorrelation analyses and a first-phase insulin secretion test was carried out.Results Prednisolone treatment led to insulin resistance as expected (HOMA-S; prednisolone vs placebo; 1.85 +/- 0.26 vs 1.02 +/- 0.10; p < 0.01) with exaggerated first-phase insulin secretion (3016 +/- 468 pmol/l vs 1688 +/- 207 pmol/l; p < 0.01), suggesting a stable disposition index. During baseline, normalized spectral power of serum insulin concentration time-series was reduced during prednisolone exposure compared with placebo (8.40 +/- 0.95 vs 11.79 +/- 1.66; p < 0.05) indicating a disturbed high-frequency oscillatory insulin release. A similar trend was observed using autocorrelation analysis (0.23 +/- 0.04 vs 0.32 +/- 0.07; p = 0.12). During glucose entrainment no difference in normalized spectral power or in the autocorrelation coefficient between prednisolone and placebo (p > 0.1) was observed.Conclusion/interpretation Six days of prednisolone treatment resulted in a pertubed high-frequency insulin release in the fasting state whereas the ability of glucose to entrain insulin secretion was preserved. This indicates a mechanism of pertubed glucose-insulin feedback mechanism which causes irregular oscillatory insulin release.

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Authors
Hollingdal, M., Juhl, C. B., Dall, R., Sturis, J., Veldhuis, J. D., Schmitz, O., & Pørksen, N.
Affiliations
  • Aarhus University Hospital (DK)
  • Novo Nordisk (Denmark) (DK)
  • U.S. National Science Foundation (US)
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2002-01-01
Volume
45
Issue
1
Pages
49-55
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s125-002-8244-y
OpenAlex
W1988096315
Cited by
67
References
36
Citations by year
2026: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 9 · 2013: 3 · 2012: 4
FWCI
3.18
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
Funders
Novo Nordisk
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, Cardiovascular Risks, and Lipoproteins
Keywords
glucocorticoid-induced insulin resistance, prednisolone, insulin pulsatility, insulin secretion, type 2 diabetes, first-phase insulin secretion
MeSH terms
Insulin Secretion, Adult, Blood Glucose, C-Peptide, Double-Blind Method, Glucocorticoids, Glucose Tolerance Test, Homeostasis, Humans, Insulin, Insulin Resistance, Kinetics, Male, Placebos, Prednisolone, Time Factors, Body Mass Index, Cross-Over Studies, Area Under Curve

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