Islet-cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance?

Metabolism. 2013 Apr;62(4):568-77. doi: 10.1016/j.metabol.2012.10.007. Epub 2012 Nov 17.


Aim: 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.

Design and 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).

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anthropometry
  • Arginine / pharmacology
  • Blood Glucose / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Glucagon / blood
  • Glucocorticoids / toxicity*
  • Glucose Clamp Technique
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Hyperglycemia / chemically induced
  • Incretins / metabolism
  • Islets of Langerhans / drug effects*
  • Male
  • Pancreatic Diseases / chemically induced*
  • Pancreatic Diseases / physiopathology
  • Pancreatic Function Tests
  • Prednisolone / pharmacology
  • Stimulation, Chemical
  • Sympathetic Nervous System / physiopathology*
  • Vagus Nerve / physiopathology*
  • Young Adult


  • Blood Glucose
  • Glucocorticoids
  • Incretins
  • Glucagon
  • Arginine
  • Prednisolone

Associated data

  • ISRCTN/ISRCTN78149983