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

M. Hollingdal, C. B. Juhl, R. Dall, J. Sturis, J. D. Veldhuis, O. Schmitz, N. Pørksen

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46 Scopus citations

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 s 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.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalDiabetologia
Volume45
Issue number1
DOIs
StatePublished - Feb 12 2002

Keywords

  • Autocorrelation
  • Deconvolution
  • Glucose entrainment
  • High frequency insulin pulsatility
  • Insulin resistance
  • Prednisolone
  • Spectral analysis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Hollingdal, M., Juhl, C. B., Dall, R., Sturis, J., Veldhuis, J. D., Schmitz, O., & Pørksen, N. (2002). Glucocorticoid induced insulin resistance impairs basal but not glucose entrained high-frequency insulin pulsatility in humans. Diabetologia, 45(1), 49-55. https://doi.org/10.1007/s125-002-8244-y