Master of Science, The Ohio State University, 2023, Veterinary Clinical Sciences

Equine metabolic syndrome is a collection of clinical and clinicopathologic findings including insulin dysregulation (ID), regional adiposity or obesity, and laminitis. Insulin dysregulation and hyperinsulinemia are associated with development of hyperinsulinemia-associated laminitis (HAL), resulting in significant welfare and financial implications. Previous research in our laboratory identified attenuation of activated 5'-adenosine monophosphate-activated protein kinase (AMPK) concentrations and increased downstream activation of mechanistic target of rapamycin (mTOR) signaling in digital lamellar tissue of horses with laminitis. Therapy with other AMPK agonists has been investigated alone and in combination (such as metformin and aspirin), yielding variable efficacy in altering ID. Since mTOR is upregulated in laminitis, resveratrol (RES) may also be an attractive therapeutic target for HAL. The purpose of this investigation was to evaluate the effects of combination treatment with RES (10 mg/kg PO q12hr), metformin (MET; 30 mg/kg PO q12hr), and aspirin (ASP; 20 mg/kg PO q24hr) on experimentally-induced ID. We hypothesized that co-administration of AMPK agonists would improve insulin and glucose dynamics in experimentally-induced equine ID. ID was induced in 33 healthy adult light-breed horses using dexamethasone (0.08 mg/kg by mouth every 24 hours). Horses were randomly assigned to one of 5 treatment groups: RES, MET/ASP, RES/ASP, RES/MET/ASP, and placebo (CON). Frequently-sampled insulin-modified IV glucose tolerance tests (FSIGTT) and oral sugar tests (OST) were performed at baseline, after 7 days of dexamethasone administration (ID), and after ID plus 7 additional days of AMPK agonist treatment. Minimal Model analysis was performed to calculate AIRg (acute insulin response to glucose), insulin sensitivity (SI), glucose effectiveness (Sg), and disposition index (DI) from the FSIGTT [insulin] and [glucose] data. Area under the curve of [insulin] (AUCins) and (open full item for complete abstract)

Committee: Teresa Burns (Committee Chair); Ramiro Toribio (Committee Member); Laura Hostnik (Committee Member) Subjects: Endocrinology

Master of Science, The Ohio State University, 2009, Veterinary Clinical Sciences

Hyperinsulinemia in horses has been shown to be related to risk of pasture associated laminitis and the equine metabolic syndrome. Additionally, some tests of endocrine function in horses, including the dexamethasone suppression test and plasma adrenocorticotropin concentration have seasonal variation. The aim of this study was two-fold, first to determine the prevalence and risk factors for hyperinsulinemia in clinically normal, adult horses and second, to determine if those concentrations vary with season. For the first part of the study, a convenience sample of 300 horses (138 mares, 143 geldings and 19 stallions; 4 to 30 years of age) was drawn from 18 farms that partially comprised the Ohio State University field service population. Plasma insulin and glucose were measured after a 10-12 hour period of grain and grass withholding. Measures of body condition score, height, weight tape and neck circumference as well as pertinent history and management practices were obtained at that time. A univariable logistic regression and a multivariable logistic regression with a random effect of farm were used to estimate odds ratios. The prevalence of hyperinsulinemia, defined by a resting insulin concentration >15 μU/L, was 22.3% (67/300). Multivariable analysis revealed that increasing age (odds ratio per year of increasing age 1.1, 95% CI 1.03-1.17) and body condition score (odds ratio 2.43, 95% CI 1.6-3.7) increased the risk for hyperinsulinemia while access to pasture (odds ratio 0.34, 95% CI 0.14-0.86) decreased the risk. Breed, sex, exercise, and measures of neck and girth circumference were not associated with risk of hyperinsulinemia. For the second part of the study, twenty-nine healthy horses, as determined by physical examination, were evaluated at three-month intervals over a one year period. Plasma insulin and glucose concentrations were measured after a 10-12 hour period of grain and grass withholding. Body condition score, height, weight tape and neck cir (open full item for complete abstract)

Committee: Laurie Gallatin DVM (Advisor); Kenneth Hinchcliff PhD (Committee Member); James Belknap DVM (Committee Member); Raymond Geor PhD (Committee Member) Subjects: Veterinary Services