Acute and 2-week exposure to prednisolone impair different aspects of β-cell function in healthy men

• Published in: European journal of endocrinology Vol. 162; no. 4; pp. 729 - 735
• Main Authors: van Raalte, Daniël H, Nofrate, Valentina, Bunck, Mathijs C, van Iersel, Thijs, Elassaiss Schaap, Jeroen, Nässander, Ulla K, Heine, Robert J, Mari, Andrea, Dokter, Wim H A, Diamant, Michaela
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.04.2010; European Society of Endocrinology
• Subjects: Adult; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; C-Peptide - blood; Clinical Study; Double-Blind Method; Drug Administration Schedule; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Glucocorticoids - administration & dosage; Humans; Insulin - blood; Insulin Resistance; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Male; Medical sciences; Middle Aged; Postprandial Period - drug effects; Prednisolone - administration & dosage; Vertebrates: endocrinology; Young Adult; Antineoplastic agent; Human; Corticosteroid; Cell function; Acute; Antiinflammatory agent; Male; Exposure; Adrenal hormone; Adult; β Cell; Immunosuppressive agent; Endocrinology; Prednisolone
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-09-1034

ObjectiveGlucocorticoids (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 β-cell function are less well established. We assessed the acute and short-term effects of prednisolone treatment on β-cell function in healthy men.Research design and methodsA 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 β-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).ResultsSeventy-five milligrams of prednisolone acutely increased the area under the postprandial glucose curve (AUCgluc; P=0.005), and inhibited several parameters of β-cell function, including AUCc-pep/AUCgluc 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 AUCgluc (P<0.001), despite augmented C-peptide secretion (P=0.05). β-cell function parameters were impaired, including the fasting insulin secretory tone (P=0.02) and PFR (P=0.007).ConclusionsAcute and short-term exposure to prednisolone impairs different aspects of β-cell function, which contribute to its diabetogenic effects.