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

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.

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.

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.

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.

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