CHAPTER 159 Insulin Resistance and Equine Metabolic Syndrome
Insulin resistance (IR) can be broadly defined as a decrease in tissue responses to circulating insulin, which causes a decrease in insulin-mediated glucose uptake into skeletal muscle, adipose, and liver tissues. Causes of IR include reduction in the density of insulin receptors on cell surfaces, malfunction of insulin receptors, defective internal signaling pathways, or interference with the translocation or function of glucose transporter proteins. Compensated IR is the most common glucose and insulin metabolism abnormality identified in horses and ponies. In this situation, serum insulin concentrations are higher than normal because more insulin is secreted from the pancreas to compensate for lower tissue responses.
Compensated IR is thought to lead to uncompensated IR if pancreatic insufficiency develops. This is sometimes also referred to as beta-cell exhaustion and is recognized when serum insulin concentration is lower than expected for the blood glucose concentration. Type 2 diabetes mellitus develops when insulin secretion can no longer compensate for the IR state and hyperglycemia develops. The term diabetes actually refers to excessive production of urine (polyuria). With type 2 diabetes mellitus, polyuria develops as a result of osmotic diuresis secondary to glucosuria. Diabetes mellitus is very rare in horses.
Insulin resistance is associated with pituitary pars intermedia dysfunction (PPID) because glucocorticoids inhibit glucose uptake into insulin-sensitive tissues such as skeletal muscle and adipose tissue and increase gluconeogenesis in the liver. This causes hyperglycemia, which preserves glucose delivery to high-priority tissues such as the brain during times of stress or danger. It is presumed that PPID induces chronic IR through increased cortisol production, but studies have not been performed to determine the relative importance of adrenocorticotropin hormone (ACTH) itself and other pituitary products, such as corticotrophin-like intermediate peptide.
Equine metabolic syndrome (EMS) is a term used to describe a collection of clinical signs that sometimes accompany insidious-onset or pasture-associated laminitis. This syndrome is currently defined by evidence of IR, obesity, or regional adiposity, and previous or existing laminitis. Clinical signs of EMS have been attributed to hypothyroidism in the past, but it is now recognized that low resting thyroid hormone concentrations accompany extrathyroidal illness in horses. Until a thyroid-stimulating hormone assay becomes commercially available, hypothyroidism should only be diagnosed by documenting an absent or blunted response to thyrotropin-releasing hormone. Ideally this diagnosis should also be supported by detection of a low rectal temperature and bradycardia. Low resting total tri-iodothyronine (tT3) and total thyroxine (tT4) concentrations detected in some obese insulin-resistant horses are a consequence rather than a cause of the observed clinical condition.
Equine metabolic syndrome is detected most commonly in ponies, Miniature horses, donkeys, and horses of the Morgan, Paso Fino, and Norwegian Fjord breeds. It has also been detected in Arabians, Quarter Horses, Saddlebreds, Tennessee Walking Horses, Thoroughbreds, and Warmbloods. Most horses are from 5 to 15 years of age when laminitis is first detected, but obesity can develop at an earlier age. Founder lines are sometimes present on hoof surfaces, indicating previous episodes of subclinical laminitis. These protruding growth rings are wider at the heel than they are dorsally and are thought to occur when laminitis inhibits dorsal hoof-wall growth. Physical characteristics of EMS include generalized obesity, regional adiposity, or both. Regional adiposity takes the form of a cresty neck in horses, and neck circumference is negatively correlated with insulin sensitivity. Other manifestations of regional adiposity include abnormal adipose tissue deposits close to the tailhead, in the prepuce, or randomly distributed beneath the skin of the trunk region (Figure 159-1).
(Courtesy of the University of Tennessee.)
Many horses are on pasture when laminitis first develops, and episodes are more common in the spring and fall. Other horses with EMS are first recognized when they are evaluated for colic, hyperlipemia, or infertility problems. Horses with EMS appear to be at greater risk for colic caused by pedunculated lipomas, and this problem seems to develop at a younger age in affected animals. Obesity and IR have been associated with reproductive problems in mares.
Equine metabolic syndrome develops when genetic and environmental factors interact. Insulin resistance follows a heritable pattern in ponies, and EMS occurs in closely related horses. Obese horses with EMS are almost always described as easy keepers because they appear to require fewer calories to maintain body weight. This concept is relevant to the issue of genetic susceptibility. Certain breeds or genetic lines may have undergone evolutionary adaptations to survive in harsher environments, and these horses or ponies are likely to be more efficient at converting poorer-quality forages into energy. Environmental factors that potentially contribute to the development of EMS include grazing on lush pasture, consumption of concentrates, and interference with seasonal weight loss.
Feeding excessive calories to genetically susceptible horses promotes obesity, and horses with EMS often have a history of overfeeding. Some concentrates, such as sweet feed, induce weight gain and also exacerbate IR. These feeds are usually rich in starches and simple sugars and create a glycemic response that can be difficult for the insulin resistant horse to accommodate. It should also be recognized that the perception of obesity differs markedly between horse owners and breed associations, so some horses are deliberately overfed to enhance their appearance.
Grass consumed on pasture sometimes provides too many calories for the genetically susceptible horse. These horses and ponies are evolutionarily adapted to grazing on poorer forages, so they rapidly gain weight when out on pasture. Depending on the climate, soil type, plant species, and drainage conditions, pasture grass can contain an abundance of nutrients, including hydrolyzable carbohydrates such as sugars that are digested and absorbed in the small intestine and fermentable carbohydrates that are primarily digested within the large intestine. Many horses and ponies with EMS will remain obese and insulin resistant for as long as they are permitted to graze on grass, even when concentrates and hay are eliminated from the diet.