title: Glucocorticoid induced insulin resistance impairs basal but not glucose entrained high-frequency insulin pulsatility in humans.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark. M.Hollingdal@dadlnet.dk
authors.forename: M
authors.initials: M
authors.lastname: Hollingdal
authors.forename: C B
authors.initials: CB
authors.lastname: Juhl
authors.forename: R
authors.initials: R
authors.lastname: Dall
authors.forename: J
authors.initials: J
authors.lastname: Sturis
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: O
authors.initials: O
authors.lastname: Schmitz
authors.forename: N
authors.initials: N
authors.lastname: Pørksen
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D010919:Placebos; D011239:Prednisolone / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005938:Glucocorticoids; D007328:Insulin; D010919:Placebos; D011239:Prednisolone