ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P242 | DOI: 10.1530/endoabs.65.P242

Glucocorticoid treatment is associated with dose-dependent effects in healthy male volunteers

Riccardo Pofi1,2, Ilaria Bonaventura1,2, Nanthia Othonos1, Thomas Marjot1, Ahmed Moolla1, Andrea M Isidori2, Leanne Hodson1 & Jeremy W Tomlinson1

1Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) and NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, UK; 2Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome, Italy

Objective: 2–3% of the population of the UK receive glucocorticoid (GC) therapy. Significant adverse effects are not confined to chronic use: recurrent short-course administration is associated with increased morbidity and mortality. Data about the cumulative dose responsible for drawbacks during GC treatment are still lacking. The aim of this study was to test the impact of 7 days of 10 or 15 mg of Prednisolone on metabolism in healthy male volunteers.

Methods: 16 healthy male volunteers were recruited from the Oxford Bio-Bank and divided into 2 age- and BMI-matched control groups as following: 6 volunteers received 10 mg of Prednisolone and 10 volunteers received 15 mg of Prednisolone for 7 days. Anthropometric and metabolic parameters were recorded and all patients underwent low dose hyperinsulinaemic–euglycaemic clamp (HEC), before (pre) and after (post) treatment. The main outcome measure was the M-value gathered from the HEC.

Results: Age, BMI and fasting blood glucose were not different between the groups at baseline. After one week of prednisolone 10 or 15 mg, no differences were found in delta (Δ=post-pre) fasting glucose (FG) (median ΔFG15mg 0.15±0.36 nmol/l vs. ΔFG10mg 0.15±0.36 nmol/l, P=0.635). However, M-value was significantly reduced in patients taking 15 mg of prednisolone (median ΔM15mg −2.5±2.0 mg/Kg per min vs. ΔM10mg −0.4±1.3 mg/Kg/min, P=0.016), as well as serum potassium (median ΔK15mg −0.3±0.2 mEq/l vs.ΔK10mg 0.10±0.18 mEq/l, P=0.011). No differences were found in Δcholesterol (total, HDL and non-HDL), liver or kidney function.

Conclusions: In this small cohort of healthy male volunteers, we demonstrated that GC treatment is associated with a worsening of insulin sensitivity through a dose-dependent effect. In addition, the decrease of serum potassium underpin the dose-dependent mineralocorticoid activity of GC. Further studies are needed to confirm our findings in larger cohort of patients.

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