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

Abstract

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 μg/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 Δ 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∙mIU/mL (p = 0.03) and Δ change values for peak insulin concentration being −100 (−167 to −29) μIU/mL (p = 0.04). No effect of pergolide treatment was detected for the ID-only group.

Main limitations

Number 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.