SFEIES24 Oral Communications Oral Communications (10 abstracts)
Differential tissue, and dose-specific adverse effects of exogenous glucocorticoids: implications for clinical practice
Riccardo Pofi 1 , Nantia Othonos 1 , Tom Marjot 1,2 , Ilaria Bonaventura 3,4 , Amy Barrett 1 , Sarah White 1 , Hamish Miller 1,5 , Tom Potter 1,6 , Conor Woods 7 , Jonathan M Hazlehurst 8 , Leanne Hodson 1 & Jeremy W Tomlinson 1
1Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, United Kingdom; 2Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 3Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, Rome, Italy; 4Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; 5Barts Liver Centre, Blizard Institute, QMUL, London, United Kingdom; 6Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, United Kingdom; 7Department of Endocrinology, Naas General Hospital, Kildare and Tallaght Hospital, Dublin, Ireland; 8Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom
Background: Prednisolone is the most prescribed exogenous glucocorticoid (GC). Despite extensive research on GC-induced side effects, key unanswered clinical questions remain about the dose threshold and tissue-specific sensitivity to adverse effects.
Aim: To compare the effects of 10, 15, and 20 mg of oral prednisolone for 7-days on the liver, skeletal muscle, adipose tissue, and bone.
Methods: We conducted a retrospective study on healthy male volunteers who participated in the FIND-IT (10 mg/day, n = 6), PUSH-UP (15 mg/day, n = 10), or TICSI (20 mg/day, n = 15) studies. Liver and skeletal muscle insulin sensitivity was assessed during a low-dose hyperinsulinaemic-euglycaemic clamp (LHEC) using stable isotope tracers to measure M/I value, endogenous glucose production (EGP), and glucose disposal (Gd) rates. Adipose tissue insulin sensitivity was evaluated through microdialysis across the LHEC and RNA-sequencing analysis of adipose tissue biopsies. Osteocalcin served as a marker for bone-related adverse effects.
Results: One week of 10 mg prednisolone did not affect liver, skeletal muscle, or adipose insulin sensitivity. However, 15 mg and 20 mg doses impaired liver and muscle glucose handling by reducing M/I value (15 mg P = 0.01; 20 mg P < 0.001) and Gd (15 mg and 20 mg P < 0.001) while increasing EGP (15 mg P = 0.005; 20 mg P = 0.04). Adipose tissue insulin sensitivity decreased in the 15 mg and 20 mg groups, as shown by increasing NEFA (15 mg P < 0.001; 20 mg P = 0.002) and glycerol levels (15 mg P < 0.001; 20 mg P = 0.002). RNA-sequencing analysis of adipose tissue biopsies demonstrated similar dysregulated gene profiles after both 10 mg and 20 mg doses. Osteocalcin levels showed similar reductions with higher prednisolone doses (15 mg P = 0.002; 20 mg P < 0.001), with published data indicating that 10 mg for 7-days reduces osteocalcin levels in healthy subjects.
Conclusions: GC-induced side effects are dose- and tissue-dependent. Compared to bone and adipose, liver and skeletal muscle appear relatively resistant to low-dose (10 mg) prednisolone. Prospective studies are needed to confirm these findings and understand their clinical implications.
Volume 104
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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