Breed differences in insulin sensitivity and insulinemic responses to oral glucose in horses and ponies of moderate body condition score

Abstract

Breed-related differences may occur in the innate insulin sensitivity (SI) of horses and ponies, an important factor believed to be associated with the risk of laminitis. The aim of this study was to measure the glucose and insulin responses of different breeds of horses and ponies in moderate body condition to a glucose-containing meal and to compare these responses with the indices of SI as determined by a frequently sampled intravenous glucose tolerance test (FSIGT). Eight Standardbred horses, 8 mixed-breed ponies, and 7 Andalusian-cross horses with a mean ± SEM BCS 5.0 ± 0.3 of 9 were used in this study. Each animal underwent an oral glucose tolerance test (OGTT) in which they were fed a fiber-based ration (2.0 g/kg BW) containing 1.5 g/kg BW added glucose, as well as a standard FSIGT with minimal model analysis. The glucose response variables from the OGTT were similar between groups; however, the peak insulin concentration was higher in ponies (94.1 ± 29.1 μIU/mL; P = 0.003) and Andalusians (85.3 ± 18.6; P = 0.004) than in Standardbreds (21.2 ± 3.5). The insulin area under the curve was also higher in ponies (13.5 ± 3.6 IU·min·L⁻¹; P = 0.009) and Andalusians (15.0 ± 2.7; P = 0.004) than in Standardbreds (3.1 ± 0.6). Insulin sensitivity, as determined by the FSIGT, was lower in Andalusians (0.99 ± 0.18 × 10⁻⁴/[mIU·min]) than in Standardbreds (5.43 ± 0.94; P < 0.001) and in ponies (2.12 ± 0.44; P = 0.003) than in Standardbreds. Peak insulin concentrations from the OGTT were negatively correlated with SI (P < 0.001; r_s = −0.75). These results indicate that there are clear breed-related differences in the insulin responses of horses and ponies to oral and intravenous glucose. All animals were in moderate body condition, indicating that breed-related differences in insulin dynamics occurred independent of obesity.

Introduction

The term equine metabolic syndrome (EMS) has been used to describe the phenotypic characteristics of animals that are at higher risk of developing laminitis [1]. The central components of EMS have been considered to be increased adiposity (generalized obesity or regional adiposity), hyperinsulinemia, and insulin resistance (IR) [1]. As yet, it has not been established whether obesity is a cause or a consequence of IR in horses or whether it is essential to the EMS phenotype. Obesity has been proposed to contribute to IR through the disruption of insulin-signaling pathways by the adipokines and proinflammatory cytokines produced by excessive amounts of adipose tissue [2]. However, IR has developed in horses independent of obesity, such as when they become adapted to diets that contain large amounts of nonstructural carbohydrates (NSCs) [3], [4]. This is presumably as a result of prolonged periods of postprandial hyperinsulinemia that causes the down-regulation of insulin receptors in target tissues. To date, it has been difficult to independently assess the role of obesity and hyperinsulinemia in the development of laminitis in horses with EMS.

A genetic basis for the EMS phenotype has been proposed [5]. It is recognized that ponies and certain breeds of horse (including Morgans, Paso Finos, and quarter horses) are more commonly affected [6], [7]. Andalusian horses (a Spanish warmblood breed) are an example of a breed predisposed to the EMS phenotype, which commonly exhibit a tendency toward obesity (‘easy keeper’) and are considered to be predisposed to laminitis [8]. However, Standardbred horses do not appear to be predisposed to obesity, IR, or laminitis. Previous studies have found oral glucose tolerance to be impaired in obese and laminitis-prone ponies compared with Standardbred horses, supporting the observation that there may be innate differences between breeds [9], [10]. A better understanding of how genetic and environmental factors contribute to the development of EMS is crucial to improving the management of horses and ponies at risk of developing laminitis [11].

The assessment of insulin sensitivity (SI) with the use of a quantitative method such as the insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) has been successfully used in horses, although its utility is generally confined to the research setting [12]. Investigators have tried to determine whether the insulinemic response of horses to a simple oral sugar test can be used as an index of IR [13], [14]. In addition to absorbed glucose, other factors such as incretin hormones may contribute to pancreatic stimulation when carbohydrates are given by the oral route [15]. Therefore, oral glucose tolerance test (OGTT) insulin responses may not necessarily correlate with FSIGT insulin responses.

The aim of this study was to examine the glucose and insulin responses of Standardbred horses, ponies, and Andalusian horses in moderate body condition to an OGTT and FSIGT. We hypothesized that ponies would have lower SI than horses, which would be reflected by increased insulinemic responses to a glucose-containing meal.