Acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men.
OBJECTIVE
Glucocorticoids (GCs), such as prednisolone, are associated with adverse metabolic effects, including glucose intolerance and diabetes. In contrast to the well known GC-induced insulin resistance, the effects of GCs on beta-cell function are less well established. We assessed the acute and short-term effects of prednisolone treatment on beta-cell function in healthy men.


METHODS
A randomised, double-blind, placebo-controlled trial consisting of two protocols was conducted. In protocol 1 (n=6), placebo and a single dose of 75 mg of prednisolone were administered. In protocol 2 (n=23), participants received 30 mg of prednisolone daily or placebo for 15 days. Both empirical and model-based parameters of beta-cell function were calculated from glucose, insulin and C-peptide concentrations obtained during standardised meal tests before and during prednisolone treatment (protocols 1 and 2), and 1 day after cessation of treatment (protocol 2).


RESULTS
Seventy-five milligrams of prednisolone acutely increased the area under the postprandial glucose curve (AUC(gluc); P=0.005), and inhibited several parameters of beta-cell function, including AUC(c-pep)/AUC(gluc) ratio (P=0.004), insulinogenic index (P=0.007), glucose sensitivity (P=0.02) and potentiation factor ratio (PFR; P=0.04). A 15-day treatment with prednisolone increased AUC(gluc) (P<0.001), despite augmented C-peptide secretion (P=0.05). beta-cell function parameters were impaired, including the fasting insulin secretory tone (P=0.02) and PFR (P=0.007).


CONCLUSIONS
Acute and short-term exposure to prednisolone impairs different aspects of beta-cell function, which contribute to its diabetogenic effects.
van Raalte
Daniël H
DH
Endocrinology Section, Department of Internal Medicine, Diabetes Centre, VU University Medical Centre, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands. d.vanraalte@vumc.nl
Nofrate
Valentina
V
Bunck
Mathijs C
MC
van Iersel
Thijs
T
Elassaiss Schaap
Jeroen
J
Nässander
Ulla K
UK
Heine
Robert J
RJ
Mari
Andrea
A
Dokter
Wim H A
WH
Diamant
Michaela
M
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage*; D055815:Young Adult
D001786:Blood Glucose; D002096:C-Peptide; D005938:Glucocorticoids; D007328:Insulin; D011239:Prednisolone