Equine laminitis: Induced by 48 h hyperinsulinaemia in Standardbred horses

Abstract

SummaryReasons for performing study: Hyperinsulinaemia is known to induce laminitis experimentally in healthy ponies with no history of the condition. Horses are more insulin sensitive than ponies and whether prolonged hyperinsulinaemia and euglycaemia would have a similar laminitogenic effect requires study. Objectives: To determine if laminitis results when the prolonged euglycaemic hyperinsulinaemic clamp technique (p-EHC) is applied to clinically normal Standardbred horses, and to monitor hoof wall temperature seeking an association between vascular activity and laminitis development. Methods: Eight young, clinically normal Standardbred horses were assigned into 4 pairs and within each pair, one was assigned randomly to either treatment (n = 4) or control (n = 4) groups. Treated horses received continuous infusions of insulin and glucose until clinical signs of laminitis developed, at which point the horses were subjected to euthanasia. Control horses received an equivalent volume of a balanced electrolyte infusion for the same period. Hoof wall surface temperature (HWST) was monitored continuously throughout the experimental period. Results: All horses in the treatment group were calculated to have normal insulin sensitivity. All treated horses, and none in the control group, developed laminitis (P = 0.01). Pronounced digital pulses were a feature of the treatment group, while insignificant digital pulses occurred in control horses. HWST was higher and less variable in treated horses once hyperinsulinaemia was established. Conclusions: Healthy Standardbred horses subjected to prolonged hyperinsulinaemia develop laminitis within 48 h, demonstrating that laminitis in horses can be triggered by insulin. Potential relevance: Insulin resistance and the associated hyperinsulinaemia place horses and ponies at risk of developing laminitis. This study demonstrates a need for prompt management of the persistent hyperinsulinaemia seen in some endocrinopathies.

Effect of Dietary Nonstructural Carbohydrate Content on Activation of 5′‐Adenosine Monophosphate‐Activated Protein Kinase in Liver, Skeletal Muscle, and Digital Laminae of Lean and Obese Ponies

“…Since the first reports of experimental laminitis induction by prolonged systemic insulin and glucose infusion were published,5, 6 much speculation has occurred regarding the most important and relevant pathophysiologic mechanisms by which laminitis develops in this setting. Initial reports suggested that laminar IR may exist, resulting in chronic glucose (carbon substrate) deprivation at the cellular level, energy failure, and dermoepidermal separation (based on in vitro experiments using laminar explants incubated in glucose‐free media for prolonged periods and subjected to mechanical distraction) 2.…”

“…Additionally, laminar basal epithelial cells (the cells that separate from their basement membrane during laminitis) do not appear to express the insulin receptor, suggesting that hyperinsulinemia may not directly affect these cells or may be activate alternate receptors (such as the insulin‐like growth factor‐1 receptor) 4. Although laminar energy dysregulation is thought to be involved in the pathophysiology of EMSAL,2, 5, 6 the mechanism or mechanisms involved remain poorly characterized.…”

Histopathological hoof laminar changes in horses with Pituitary Pars Intermedia Adenoma: cases report

“…The result obtained by the authors suggests that the separation of the BM occurs secondary to initial injury, since it was possible to observe morphological changes related to the nuclei of the BC and organization of primary epidermal laminae (PEL) and secondary epidermal laminae (SEL) prior to the change of BM. de Laat et al (2010) observed the development of laminitis after insulin administration with clinical manifestation of the disease, such as hoof sensitivity and lameness, and with the histopathological assessment of the laminar tissue showing cell proliferation, thinning of SEL, rounded BC oriented perpendicular to the BM. However, these findings differ from those described by Pollitt (1996) in its classification as grade 3 associated with obvious symptoms of laminitis, such as the absence of BM and severe destruction of the lamellar architecture of the hoof.…”

An update on equine laminitis

“…Horses affected by Cushing's syndrome, obese animals or the ones receiving high and prolonged concentrations of glucocorticoids (RYU et al, 2004, DE LAAT et al, 2010 show endocrine disorders, such as hyperglycemia, hyperinsulinemia and insulin resistance (DE LAAT et al, 2010). The endochrinopathy laminitis is evidenced by milder clinical signs in comparison with laminitis secondary to inflammatory diseases, and in some animals it may occur rotation of the distal phalanx with hoof structural changes, with less intense painful discomfort which can be inconspicuous or absent (JOHNSON, 2002a).…”

“…The disease can also be induced in healthy horses via insulin administration (DE LAAT et al, 2010), in an experimental model related to secondary laminitis to endocrine changes. BELKNAP et al (2011) ischemia can also promote lesions in the laminar tissue (RIO TINTO et al, 2004;LASKOSKI et al, 2010), which is supported by severe changes in laminar tissue reported in horses with natural colic syndrome not yet evidencing clinical signs of foot disease (LASKOSKI et al, 2009).…”