Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation.

Abstract

BACKGROUND: Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia-associated laminitis, but in diabetic people nonsteroidal anti-inflammatory drugs increase insulin secretion and pancreatic activity. HYPOTHESIS/OBJECTIVES: Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID). ANIMALS: Sixteen light breed horses, including 7 with ID. METHODS: Randomized cross-over study design. Horses underwent an oral glucose test (OGT) after 9&#x2009;days of treatment with phenylbutazone (4.4&#x2009;mg/kg IV q24h) or placebo (5&#x2009;mL 0.9% saline). After a 10-day washout period, horses received the alternative treatment, and a second OGT was performed. Insulin and glucose responses were compared between groups (ID or controls) and treatments using paired t test and analyses of variance with P&#x2009;<&#x2009;.05 considered significant. RESULTS: In horses with ID, phenylbutazone treatment significantly decreased glucose concentration (P&#x2009;=&#x2009;.02), glucose area under the curve (2429&#x2009;&#xb1;&#x2009;501.5 vs 2847&#x2009;&#xb1;&#x2009;486.1&#x2009;mmol/L&#x2009;&#xd7;&#x2009;min, P&#x2009;=&#x2009;.02), insulin concentration (P&#x2009;=&#x2009;.03) and insulin area under the curve (17&#x2009;710&#x2009;&#xb1;&#x2009;6676 vs 22&#x2009;930&#x2009;&#xb1;&#x2009;8788&#x2009;&#x3bc;IU/mL&#x2009;&#xd7;&#x2009;min, P&#x2009;=&#x2009;.03) in response to an OGT. No significant effect was detected in control horses. CONCLUSION AND CLINICAL IMPORTANCE: Phenylbutazone administration in horses with ID decreases glucose and insulin concentrations in response to an OGT warranting further investigation of a therapeutic potential of phenylbutazone in the management of hyperinsulinemia-associated laminitis beyond analgesia.