Dexamethasone administration transiently increases insulin response to an oral carbohydrate challenge in horses.

Abstract

Objective: Dexamethasone is used to experimentally induce insulin resistance; however, its impact on insulin secretion is unclear. This study aimed to assess the responses to oral carbohydrate challenges in dexamethasone-treated horses.

Methods: 8 healthy Standardbreds received 0.08 mg/kg of dexamethasone IM every 48 hours for 14 days in June 2022 (winter in the Southern hemisphere). Oral glucose tests (OGT) were conducted before treatment (day 1) and on days 8 and 15. Glucose, insulin, triglycerides, total and active glucagon-like peptide-1 (tGLP-1 and aGLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were measured at baseline and at intervals up to 240 minutes after OGT. The results were analyzed using a mixed-effects linear regression model.

Results: After 8 days of dexamethasone, significant increases in areas under the curve (AUC) of glucose (effect size, +139.1 [95% CI, 124.0 to 154.1] mg/dL·min), insulin (+297.6 [95% CI, 214.6 to 380.8] µIU/mL·min), triglycerides (+4,854.3 [95% CI, 2,181.3 to 7,527.3] mg/dL·min), tGLP-1 (+2.58 [95% CI, 0.23 to 4.93] pmol/L·min), and GIP (+65.56 [95% CI, 40.98 to 90.16] pg/mL·min) were detected post-OGT. These effects were blunted by day 15, with glucose, insulin, and active glucagon-like peptide-1 AUC significantly lower than on day 8 and tGLP-1, triglycerides, and GIP AUC not different from day 1. No horse developed clinical laminitis.

Conclusions: Dexamethasone increased insulin secretion after an OGT with higher lipid mobilization and stimulation of the enteroinsular axis, but the effect was partially reversed by day 15.

Clinical relevance: While dexamethasone induces insulin resistance consistently over prolonged periods, its effect on insulin secretion seems transient.