Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial

• Published in: Diabetologia 2011-08, Vol.54 (8), p.2103-2112
• Main Authors: van Raalte, D. H., Brands, M., van der Zijl, N. J., Muskiet, M. H., Pouwels, P. J. W., Ackermans, M. T., Sauerwein, H. P., Serlie, M. J., Diamant, M.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biological Transport - drug effects; Blood Glucose - drug effects; Body fat; Diabetes; Diabetes. Impaired glucose tolerance; Disease; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Glucocorticoids - pharmacology; Glucose; Human Physiology; Humans; Insulin - metabolism; Insulin resistance; Internal Medicine; Lipolysis - drug effects; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Musculoskeletal system; Prednisolone - administration & dosage; Prednisolone - adverse effects; Prednisolone - pharmacology; Proteins; Young Adult
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2174-9

Aim/hypothesis To assess whether low-dose glucocorticoid treatment induces adverse metabolic effects, as is evident for high glucocorticoid doses. Methods In a randomised placebo-controlled double-blind (participants and the investigators who performed the studies and assessed the outcomes were blinded) dose–response intervention study, 32 healthy men (age 22 ± 3 years; BMI 22.4 ± 1.7 kg/m 2 ) were allocated to prednisolone 7.5 mg once daily ( n  = 12), prednisolone 30 mg once daily ( n  = 12), or placebo ( n  = 8) for 2 weeks using block randomisation. Main outcome measures were glucose, lipid and protein metabolism, measured by stable isotopes, before and at 2 weeks of treatment, in the fasted state and during a two-step hyperinsulinaemic clamp conducted in the Clinical Research Unit of the Academic Medical Centre, Amsterdam, the Netherlands Results Prednisolone, compared with 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