Dose-dependent and tissue-specific adverse effects of exogenous glucocorticoids: insights for optimizing clinical practice.
Pofi R., Othonos N., Marjot T., Bonaventura I., Barrett A., White S., Miller H., Potter T., Bailey M., Eastell R., Gossiel F., Woods C., Hazlehurst JM., Hodson L., Tomlinson JW.
PURPOSE: There is limited data on dose-specific metabolic effects of exogenous glucocorticoids (GC) doses. This study aimed to investigate the differential tissue-specific and dose-dependent effects of low-to-intermediate prednisolone doses on insulin sensitivity and bone metabolism in healthy individuals. METHODS: We performed a post-hoc pooled analysis of three independent clinical trials, each administering one week of daily prednisolone at 10 mg, 15 mg, or 20 mg, in a total of 30 different healthy male volunteers (aged 18-65; BMI 20-35 kg/m²; normal kidney function). Outcome measures included: changes in liver (endogenous glucose production-EGP, β-hydroxybutyrate-OHB), muscle (M/I value, Glucose disposal-Gd) and adipose tissue (NEFA, glycerol) insulin sensitivity assessed across a hyperinsulinemic-euglycemic clamp. Bone turnover was evaluated through osteocalcin levels. RESULTS: Prednisolone 10 mg had minimal impact on metabolic parameters. 15 mg and 20 mg caused similar reductions (no dose effects) in liver (time effect p