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

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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.

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