2017 ACVIM Forum Research Abstract Program

ber type area or proportion. There were breed differences in adipocyte, but not muscle histology. The weak correlations between BCS, TBFM and SI and AIRg suggest that adiposity may not be a key factor in determining metabolic fitness in horses. Equine metabolic syndrome (EMS), a clustering of metabolic disturbances resulting in insulin dysregulation and derangements in fat metabolism, is the most common cause of laminitis. Previous work from our lab has confirmed that the pathophysiology of EMS is complex, with both genetic and environmental factors contributing to the phenotypic variability in metabolic traits. The objective of this project was to identify genomic regions contributing to EMS by performing a genome-wide association study (GWAS) in a cohort of 232 Welsh ponies and 286 Morgan horses phenotyped for 11 metabolic traits. Genotyping was performed on one of three SNP arrays (54,000, 670,000 to 1,800,000 SNPs); genotype imputation allowed for generation of a uniform set of makers across platforms (~1.8 million SNPs). GWAS was performed using a mixed linear regression model with sex and age included as covariates. Within breeds, a total of 67 (Welsh ponies) and 116 (Morgans) significant loci were identified for the metabolic traits, of which 4 were shared between breeds. Loci were defined as shared if SNPs with a P-value < 1.00e-05 were within a 500 kb window of each other. Specifically, shared loci were identified on ECA10, ECA18, ECA20, and ECA3 for insulin levels post oral sugar test, and baseline non-esterified fatty acids, triglycerides, and ACTH, respectively, with a total of 75 candidate genes identified. These data confirm that EMS is a polygenic trait with risk loci unique to individual breeds as well as those shared between breeds. Future directions include interrogation of these regions through whole genome sequencing. The relationship between insulin dysregulation, dietary adaptation and aging is poorly understood yet critical to making dietary recommendations for horses at risk of insulin dysregulation and associated laminitis. In this study, the effect of age and diet on insulin and glucose dynamics was examined in 16 healthy Thoroughbred and Standardbred horses, divided into two groups: Adult (8.8 AE 2.9 years; mean AE SD) and Aged (20.6 AE 2.1 years). Four concentrate isocaloric diets: Base (low starch, low sugar), Starch (base plus kibbled corn), Fiber (base plus beet pulp and soybean hulls), and Sugar (base plus dextrose powder) were each fed for seven weeks (balanced four-way crossover). Horses were group fed low non-structural carbohydrate hay once daily, and individually fed concentrate meals twice daily. In the seventh week, insulin-modified frequently sampled intravenous glucose tolerance tests and oral sugar tests (OST) (0.25 mL/kg corn syrup) were performed. Data were analyzed with multivariable linear mixed regression (significance set at P ≤ 0.05). Acute insulin response to glucose (AIRg), OST_peak insulin, insulin area under the curve, and OST_insulin 75 minutes were higher in Aged than Adult independent of diet. Aged had higher AIRg and disposition index on Fiber and Sugar, and glucose effectiveness on Sugar than Adults adapted to the same diet. Adults had lower OST_insulin basal on Fiber compared to Sugar. Aged horses had higher OST_peak insulin than Adults on Fiber. Age and diet had an influence on insulin and glucose dynamics, and should be considered when evaluating a horse's metabolic status. Di