2 - TI Pharma

Chapter 8 Glucocorticoids affect intermediary metabolism
ABSTRACT
objectives: To assess whether low-dose glucocorticoid (GC) treatment induces adverse
metabolic effects, as is evident for high GC doses.
Methods: In a randomized, placebo-controlled, double blind, dose-response intervention
study, 32 healthy males (age: 22±3 years; BMI 22.4±1.7 kg/m2 ) 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 using block randomization. Mean outcomes measures were glucose-,
lipid- and protein metabolism, as measured by stable isotopes, before and at 2 weeks of
treatment, in the fasted state and during a two-step hyperinsulinemic clamp.
Results: Prednisolone, as compared to placebo, dose-dependently and significantly
increased fasting plasma glucose levels, whereas only prednisolone 30 mg increased
fasting insulin levels (29±15 pmol/l). Prednisolone 7.5 mg and prednisolone 30 mg
decreased the ability of insulin to suppress endogenous glucose production (by 17±6%
and 46±7%, respectively, vs. placebo). Peripheral glucose uptake was not reduced by
prednisolone 7.5 mg, but was decreased by prednisolone 30 mg by 34±6% (P