Corticosteroid Administration Enhances the Glycemic, Insulinemic, and Incretin Responses to a High‐Protein Mixed Meal in Adult Horses

ABSTRACT Background Corticosteroids are used routinely in horses and induce insulin dysregulation (ID). Nutrition is important for ID management and includes low nonstructural carbohydrate (NSC) diets and, often, high‐protein ration balancers (RB). Insulin and incretin secretion increase after high‐protein meals; corticosteroids may influence these effects. Hypothesis A high‐protein mixed meal will induce hyperinsulinemia and increased concentrations of glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide 1 (GLP‐1) in horses with ID; dexamethasone (DEX) will amplify this effect. Animals Five horses with naturally occurring ID. Methods Horses underwent an IV glucose tolerance test and a feed challenge test (FCT; 1 kg RB). Tests were repeated after DEX administration (0.08 mg/kg PO q24h, 7 days). Insulin, glucose, and incretin dynamics were compared pre‐ and post‐DEX. Results Corticosteroids exacerbated post‐prandial hyperinsulinemia and hyperglycemia after a high‐protein meal. The FCT area under the curve for insulin (AUCINS) after DEX was significantly higher than baseline (558 ± 182 μIU/mL × min vs. 257 ± 93.9 μIU/mL × min; p = 0.03). The maximum concentration of GIP (CmaxGIP) after DEX (381 ± 70.6 pg/mL) was significantly higher than baseline (262 ± 13.7 pg/mL; p = 0.013). The AUC for GLP‐1 (AUCGLP‐1; 31.1 ± 15.2 vs. 50 ± 20.2 pg/mL; p = 0.19) and the Cmax of GLP‐1 (CmaxGLP‐1; 39.1 ± 25.3 vs. 29.6 ± 12.2 pg/mL; p = 0.32) did not differ between DEX and baseline. Conclusions and Clinical Importance Metabolic responses to a high‐protein mixed meal were exacerbated by corticosteroids. Horses receiving corticosteroids had larger GIP responses, which may enhance post‐prandial hyperinsulinemia.