Metabolic profiling of hyperinsulinemic horses

Insulin dysregulation mediates the increased risk for laminitis associated with the two most common equine endocrinopathies, pituitary pars intermedia dysfunction (PPID) and the equine metabolic syndrome (EMS). This thesis aimed to describe the metabolic profile of horses with this condition to help elucidate the cause for the increased insulin production it elicits and possibly uncover some pathomechanisms leading to laminitis. Besides identifying metabolites correlated to the level of the insulin response to an oral glucose test, such as carnitine, arginine and DOPA, this project revealed the potential of such molecules in recognizing horses with insulin dysregulation without complex diagnostic tests. Additionally, it allowed to concretely quantify the reduction of the insulin response to oral carbohydrates following weight loss, while differentiating the respective metabolic impact of weight gain and worsened insulin dysregulation. Lastly, metabolites associated with subsequent laminitis were described. Altogether, the results provided new concepts for the identification of insulin dysregulation, supported an association between this condition and vascular dysfunction, helped distinguish the metabolic impact of weight variations from the effect of insulin dysregulation, and suggested that carnitine and arginine could be investigated as nutritional supplements to treat insulin dysregulation.