Effect of pergolide treatment on insulin dysregulation in horses and ponies with pituitary pars intermedia dysfunction

Background: Due to the high frequency of laminitis reported for both conditions, the relationship between pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID), and the potential role of dopamine in modifying insulin secretion, requires further investigation. Objectives: To evaluate the effect of pergolide mesylate on insulin sensitivity and postprandial insulin and glucose responses in horses and ponies with ID, both with or without concurrent PPID. Study design: Randomised crossover study. Methods: Sixteen horses and ponies, comprising eight matched pairs (PPID+ID or ID-only), were given pergolide mesylate at a dose of 2 mu g/kg bwt orally once daily for 4 weeks (plus a 4-week non-treatment control period, with a 4-week washout between phases). A combined glucose and insulin tolerance test (CGIT) and a standard meal test (SMT; containing 1.1 g/kg bwt of starch and 0.1 g/kg bwt of free sugars), were performed before and after each treatment period to determine insulin sensitivity and postprandial insulin and glucose responses, respectively. Variables derived from the CGIT and SMT were analysed using linear mixed models. Results: Pergolide treatment did not alter any of the variables derived from the CGIT in either the PPID+ID or ID-only groups (all p > 0.05). For the SMT, insulin responses were reduced by pergolide treatment for the PPID+ID group, with Delta change values for the total area under the curve for insulin over 300 mins (estimated marginal mean [95% confidence interval]) being -25.4 (-39.9 to -7.3) min center dot mIU/mL (p = 0.03) and Delta change values for peak insulin concentration being -100 (-167 to -29) mu IU/mL (p = 0.04). No effect of pergolide treatment was detected for the ID-only group. Main limitationsNumber of animals and heterogeneity among groups. Conclusions: Pergolide had no effect on tissue insulin sensitivity. However, the results suggest that postprandial hyperinsulinaemia may be limited by this dopamine receptor agonist in animals with PPID plus ID.