title: Islet-cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance?
abstract: OBJECTIVE
  Glucocorticoids 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  We 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).
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: 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
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.forename: Kelly A A
authors.initials: KA
authors.lastname: Kwa
authors.forename: Renate E
authors.initials: RE
authors.lastname: van Genugten
authors.forename: Maarten E
authors.initials: ME
authors.lastname: Tushuizen
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.forename: John M
authors.initials: JM
authors.lastname: Karemaker
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000293:Adolescent; D000328:Adult; D000886:Anthropometry; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005934:Glucagon / Q000097:blood; D005938:Glucocorticoids / Q000633:toxicity*; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D054795:Incretins / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D010182:Pancreatic Diseases / Q000139:chemically induced* / Q000503:physiopathology; D010186:Pancreatic Function Tests; D011239:Prednisolone / Q000494:pharmacology; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014630:Vagus Nerve / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D054795:Incretins; D005934:Glucagon; D001120:Arginine; D011239:Prednisolone