Impact of therapeutic doses of prednisolone and other glucocorticoids on insulin secretion from human islets

Abstract

Introduction: Glucocorticoid-induced diabetes (GCID) is a prevalent health issue, generally attributed to insulin resistance. High doses of dexamethasone (DEX) are known to inhibit glucose-stimulated insulin secretion (GSIS), but the effects of lower doses, commonly used in chronic therapy, and equipotent doses of other glucocorticoids (GCs) such as hydrocortisone (HC) and prednisone (PRED) remain underexplored. This study aimed to investigate these effects in vitro, and explore variations between patients.

Materials and methods: Dynamic perifusion assays were conducted on human islets to evaluate the impact of different GCs on GSIS. The islets were treated for 24h with 250nM PRED and other GCs at equipotent anti-inflammatory doses (HC: 1μM; DEX: 38nM).

Results: In 11 human islet donor preparations, 250nM PRED, corresponding to a clinical oral dose of 5mg/day, significantly inhibited the first and second phase of GSIS: area under the curve (AUC) decreased by 32.3% (P<0.001), first phase by 41.5% (P<0.001), and second phase by 38.4% (P<0.001). Despite interindividual differences in GSIS response to PRED, no significant differences were observed according to body mass index, gender or age. Comparing the effects of GCs at equipotent anti-inflammatory doses, DEX had a more pronounced inhibitory effect on GSIS than HC or PRED.

Conclusions: In vitro, low-dose PRED treatment significantly impacted GSIS. DEX had a more unfavorable impact on GSIS than HC or PRED, indicating that metabolic effects do not align with anti-inflammatory potency.

Keywords: Diabetes; Glucocorticoids; Human islets; Hyperglycemia; Insulin secretion.