Equine metabolic syndrome (EMS) describes a characteristic collection of clinical signs and clinicopathologic changes in equids. It is found in both horses and ponies and has also been recognized in donkeys. Affected animals typically are obese with increased condition score overall and increased adiposity in the neck and tailhead regions. Laminitis, both chronic and acute, is common. Hyperinsulinemia with normal blood glucose concentrations (insulin resistance) is the primary clinical pathologic finding. Other associated signs include infertility, altered ovarian activity, and increased appetite. Other laboratory findings include hypertriglyceridemia, increased serum concentrations of leptin, increased systemic markers of inflammation, and arterial hypertension. Previously, this cluster of clinical signs in horses has been referred to as hypothyroidism, peripheral Cushing's disease, prelaminitic syndrome, or Syndrome X. EMS replaces these earlier terms.
EMS first develops in horses that are 5–16 yr old. Breeds most commonly affected include ponies, Saddlebred, Tennessee Walking, Paso Fino, Morgan, Mustang, and Quarter horse. Thoroughbreds and Standardbreds infrequently develop EMS. There is no recognized sex predilection.
Etiology and Pathogenesis
The underlying reason why some horses develop EMS and others do not is not known. There appears to be a genetic disposition, both within and between breeds. Affected animals may possess a “thrifty” gene that enabled their ancestors to survive in harsh environments. This increased efficiency of energy metabolism became maladaptive in modern environments with plentiful, nutrient-dense feedstuffs.
The common denominators behind many of the signs associated with EMS appear to be increased adiposity, insulin resistance, and hyperinsulemia. When obesity develops, adipose tissues elaborate leptin and other adipokines as well as tumor necrosis factor and other inflammatory mediators. This may lead to a vicious cycle of increasing adipocyte inflammation as more and more inflammatory cells are attracted to adipose tissue as a result of these increased inflammatory mediator concentrations. Increased fat stores in the liver may also predispose to insulin resistance due to down-regulation of insulin receptors.
Insulin has vasoregulatory actions. Insulin resistance can decrease nitric oxide production and promote vasoconstriction. Altered glucose and insulin levels may also lead to altered epidermal cell function and glucose uptake by epidermal laminar cells. These effects predispose horses with EMS to develop laminitis.
Horses with EMS respond to high carbohydrate meals with an exaggerated increase in insulin and a very slow return to baseline values. This indicates a resistance to the peripheral effects of insulin and an inability to metabolize carbohydrate normally.
EMS may be a predisposing factor for pituitary pars intermedia dysfunction (PPID; also called equine Cushing's disease). Both endocrine disorders can occur concurrently in middle-aged and older horses. Horses with EMS should therefore be monitored to detect the onset of PPID.
There is no clinical picture that is pathognomonic for insulin resistance. Horses may exhibit all the phenotypic characteristics of EMS with normal responses to evocative testing. In most instances, the animals in question are obese due to excess calorie intake rather than any underlying metabolic alteration.
Affected horses typically are obese with a body condition score >6 out of 9. Even if the overall condition score is not extremely elevated, there is increased fat deposition in the neck, leading to a “cresty” appearance. Fat deposition over the ribs and over the top line to the tail head is also common. Geldings may have increased fat deposition in the prepuce, while mares may have increased fat deposition around the mammary gland. Laminitis is a common finding. Horses brought in for evaluation with no previous history of laminitis often show evidence of prior episodes such as abnormal hoof growth rings and radiographic evidence of third phalanx rotation. Laminitis may occur secondary to ingestion of feeds high in soluble carbohydrates, either in the form of lush pasture or high-carbohydrate hays and supplements. This can result in bouts of laminitis developing in the spring, when new pasture growth appears, and in the fall, when night temperatures are below freezing.
Horses with EMS may not lose weight without extreme feed restriction; owners commonly report that affected horses remain obese even when fed minimal amounts. Obesity may be exacerbated by laminitis, which may limit exercise. Horses appear to have increased appetites and often will eat continuously as long as feed is available. Infertility and abnormal reproductive cycles occur in mares affected with EMS.
Increased general adiposity and laminitis are often documented. The pituitary gland is normal in younger horses with EMS, but lesions consistent with PPID may be found in older horses with EMS that are concurrently affected by EMS and PPID.
Diagnostic testing for EMS should concentrate on documenting insulin resistance while ruling out PPID. The presence of obesity and the cresty neck phenotype is not sufficient to make a diagnosis. A careful dietary history and physical examination are essential. Establishing baseline body condition score and neck circumference will enable owners and practitioners to assess the horse's response to treatment. Even if there is no history of laminitis, careful examination of the feet, including lateral images of P3, are indicated.
Because many conditions including diet, pain, and stress can affect blood glucose and insulin levels, diagnostic testing should be performed in a controlled manner in a low-stress environment. If the horse has laminitis, diagnostic testing should be delayed until the feet have stabilized and are relatively pain free.
Blood glucose concentrations are in the normal range or only slightly elevated with EMS. If persistent hyperglycemia is documented, concurrent PPID should be strongly suspected. Because many factors influence blood glucose and insulin levels, a one-time blood insulin measurement should only be used as a screening test for insulin resistance. Insulin should be determined after the horse has been fasted for 6–8 hr. These conditions can be met by leaving only one flake of hay with the horse after 10 PM the night before and then collecting the blood sample the next morning. If those conditions are met, a blood insulin concentration >20 μU/mL is suggestive of insulin resistance.
To document insulin resistance, the horse's ability to handle an increased glucose load should be evaluated. This can be done via oral or IV glucose tolerance testing or a combined glucose-insulin response test. The oral glucose tolerance test can be altered by delayed gastric emptying or poor GI absorption and is less desirable. The combined glucose-insulin test provides the most information in the shortest period of time, and is the preferred diagnostic test. Because of the large number of blood samples required and the fact that change from baseline—not absolute glucose values—is of interest, a hand-held glucometer may be used when performing these tests.
Tests for PPID such as the dexamethasone suppression test, domperidone response test, and thyroid releasing hormone response test are normal in horses with EMS. Positive results indicate that the horse is concurrently affected by EMS and PPID, which can occur in older horses. Detection of PPID is important because it is thought that PPID exacerbates insulin resistance in horses previously affected by EMS.
Treatment and Prevention
Treatment for EMS involves dietary management and, if diet and exercise is not sufficient to treat the condition, medical therapy. Correction of the diet may be all that is needed to return the animal to normal body weight. Dietary carbohydrate restriction is essential to decrease glycemic and insulinemic response; total calorie intake is restricted in order to reduce body weight. Pasture access should be eliminated or severely restricted. Use of a grazing muzzle may aid in decreasing pasture ingestion.
The nonstructural carbohydrate (NSC) content of forage should be determined by feed analysis. This can be calculated by adding starch and water soluble carbohydrate percentages. Ideally NSC should comprise <10% of the hay dry matter. Soaking hay in water for 60 min has been recommended to lower water-soluble carbohydrate concentrations, but the actual amount reduced is extremely variable and this is not a reliable method to produce a low-NSC forage. Supplements should be given to add needed vitamins and minerals, but not additional calories. Complete feeds that are formulated to be low in digestible energy and carbohydrate specifically designed for horses with insulin resistance may be used in place of forage and supplements. Numerous dietary supplements have been suggested to increase insulin sensitivity, including cinnamon, chromium, and magnesium. None have been shown to improve insulin sensitivity in horses in experimental situations.
Horses should initially be fed 1.5% of their ideal body weight in forage per day. This amount can be lowered to 1.0% of ideal body weight after 30 days, if necessary. Sudden feed restriction should be avoided because it may lead to hyperlipemia and further exacerbate insulin resistance. Increasing the amount and level of exercise will increase the rate of weight loss. The amount of exercise necessary to provide maximal benefits has not been established, but 5 sessions per week that include at least 30 min of trotting and lungeing is a realistic goal. In horses with laminitis, walking as pain allows may be of some benefit.
Weight reduction should be documented by scale weight or weight tapes. In addition, neck thickness and diameter can be monitored over time. If increased exercise and dietary modification is not sufficient to decrease body weight, medical therapy may be of benefit.
The thyroid hormone thyroxine, in the form levothyroxine sodium, will accelerate weight loss and thereby improve insulin sensitivity when combined with dietary interventions in horses. Horses >350 kg can be given 48 mg/day, PO; smaller horses and ponies should receive 24 mg/day, PO. Treatment periods of 3–6 mo are often needed to achieve desirable weight loss. At that time, the horse can be weaned off the medication over 3–4 wk. If feed intake is not limited concurrently, treatment with levothyroxine is unlikely to resolve clinical signs.
Metformin increases insulin sensitivity through its effects on insulin signaling pathways and lowers blood glucose concentrations by inhibiting gluconeogenesis and glycogenolysis. It has been reported to lead to improvement in hyperinsulinemic horses at a dosage of 15 mg/kg, PO, bid. The longterm efficacy and safety of metformin has not been established in horses, however. If it is used, blood glucose should be carefully monitored. Use of metformin should be discontinued if hypoglycemia is documented.
Prevention of EMS should focus on maintaining normal weight in horses, particularly those that are high-risk breeds. Because these animals may be more efficient users of ingested calories than others, it is imperative to feed to maintain an ideal condition score and not to use arbitrary feeding guidelines. Particular care should be exercised when turning animals on pasture during times of high soluble carbohydrate content, eg, spring and autumn.
Last full review/revision July 2011 by Janice E. Kritchevsky, 'VMD, MS, DACVIM