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

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 ± 2 years; BMI: 21.9 ± 1.7 kg/m2). Participants were allocated to prednisolone 7.5 mg once daily (n = 12), prednisolone 30 mg 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) nmol L− 1 min− 1 for prednisolone 7.5 mg and prednisolone 30 mg, 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 30 mg. 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.