• Daniël H van Raalte, Kelly A A Kwa, Renate E van Genugten, Maarten E Tushuizen, Jens J Holst, Carolyn F Deacon, John M Karemaker, Robert J Heine, Andrea Mari, and Michaela Diamant.
• Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1007MB, PO Box 7057, Amsterdam, The Netherlands. d.vanraalte@vumc.nl
• Metab. Clin. Exp. 2013 Apr 1; 62 (4): 568-77.

AimGlucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system.Design And MethodsA randomized, placebo-controlled, double-blind, dose-response intervention study was conducted in 32 healthy males (age: 21±2years; BMI: 21.9±1.7kg/m(2)). Participants were allocated to prednisolone 7.5mg once daily (n=12), prednisolone 30mg once daily (n=12), or placebo (n=8) for two weeks. Beta-cell function was measured by hyperglycemic clamp with arginine stimulation, glucagon levels were measured following a standardized meal test.ResultsWe found that prednisolone treatment dose-dependently reduced C-peptide secretion following arginine stimulation on top of hyperglycemia (ASI-iAUCCP): -2.8 (-5.2;0.2) and -3.1 (-8.8; -1.0) nmolL(-1)min(-1) for prednisolone 7.5mg and prednisolone 30mg, respectively (P=0.035 vs. placebo). Fasting glucagon levels increased dose-dependently (vs. placebo; P=0.001), whereas postprandial glucagon levels were only increased by prednisolone 30mg. Changes in parasympathetic activity related with changes in fasting glucose levels (r=-0.407; P=0.03) and showed a trend towards correlation with fasting glucagon concentrations (r=-0.337; P=0.07). The change in sympathovagal balance was inversely related to ASI-iAUCCP (r=-0.365; P=0.05).ConclusionWe conclude that in addition to inducing insulin resistance, prednisolone treatment dose-dependently impaired islet-cell function. Altered sympathovagal balance may be related to these effects.Copyright © 2013 Elsevier Inc. All rights reserved.

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