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

Abstract

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/AUCglucratio (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.