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Professional Version

Equine Metabolic Syndrome

(Insulin Dysregulation)

By

Janice E. Kritchevsky

, VMD, DACVIM-LAIM, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University

Reviewed/Revised Dec 2023
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  • The SGLT-2 inhibitors pioglitazone, ertugliflozin, and velagliflozin have improved insulin dysregulation in equine research studies.

Topic Resources

Equine metabolic syndrome is a collection of clinical signs and clinicopathologic changes that are due to the inability of some equids to respond normally to dietary carbohydrates (insulin dysregulation). Laminitis is the most important morbidity; however, preputial and mammary swelling, obesity, and infertility also occur. Diagnosis is based on measuring increased insulin secretion after a carbohydrate challenge. The condition is best controlled by limiting carbohydrate intake. If changes to diet and exercise are not sufficient, pharmacologic agents may be needed to decrease insulin concentrations.

Equine metabolic syndrome (EMS) is a characteristic collection of clinical signs and clinicopathologic changes in equids that places them at high risk for developing laminitis Laminitis in Horses The horse hoof. Median section through the horse digit. Equine laminitis is a crippling disease in which there is a failure of attachment of the epidermal laminae connected to the hoof wall... read more Laminitis in Horses . Insulin dysregulation is the key feature of the syndrome.

EMS 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 regional adiposity in the neck and tailhead regions (see ). Laminitis, both chronic and acute, is common.

Hyperinsulinemia with normal blood glucose concentrations (insulin dysregulation) is the primary clinicopathologic finding for EMS. Other associated clinical signs include infertility, altered ovarian activity, preputial swelling, and increased appetite.

Additional laboratory findings for EMS include hypertriglyceridemia, increased serum concentrations of leptin, and arterial hypertension.

Historically, this cluster of clinical signs in horses was referred to as hypothyroidism, peripheral Cushing disease, prelaminitic syndrome, or syndrome X. "Equine metabolic syndrome" replaces those earlier terms.

EMS may be the end result of an inability to properly metabolize dietary carbohydrate. Many affected horses exhibit exaggerated glucose and insulin responses to an oral hexose load before developing true insulin dysregulation.

EMS has the following typical patterns of development in different equids:

  • In horses, it arises between the ages of 5 and 16 years, with no recognized sex predilection.

  • It is most common in ponies and in the Saddlebred, Tennessee Walking Horse, Paso Fino, Morgan, Mustang, and Quarter horse breeds.

  • It occurs infrequently in Thoroughbreds and Standardbreds.

Etiology and Pathogenesis of Equine Metabolic Syndrome

The underlying reason why some horses develop EMS and others do not is not known. However, there appears to be a genetic disposition, both within and between breeds.

Horses with EMS may possess a “thrifty” gene that enabled their ancestors to survive in harsh environments but has become maladaptive in modern environments with plentiful, nutrient-dense feedstuffs.

The common denominators of many clinical signs associated with EMS appear to be increased adiposity, insulin dysregulation, and hyperinsulinemia.

When obesity develops, adipose tissues elaborate leptin and other adipokines, as well as tumor necrosis factor and other inflammatory mediators. Increased fat stores in the liver may also predispose the affected animal to insulin dysregulation because of the downregulation of insulin receptors.

Experimentally, high blood insulin concentrations lead to laminitis in horses and ponies.

  • Insulin has vasoregulatory actions. Insulin dysregulation can decrease nitric oxide production and promote vasoconstriction.

  • Altered glucose and insulin concentrations may also lead to altered epidermal cell function and glucose uptake by epidermal laminar cells.

Horses with EMS show the following responses to high-carbohydrate meals:

  • exaggerated increase in insulin

  • higher-than-expected blood glucose concentrations

  • very slow return of blood glucose concentrations to baseline values

These responses indicate a resistance to the peripheral effects of insulin (EMS) and/or an inability to metabolize oral carbohydrate normally (insulin dysregulation).

Pituitary pars intermedia dysfunction Hypertrichosis Associated with Adenomas of the Pars Intermedia Acquired hypertrichosis (excessive hair growth) is invariably associated with pituitary pars intermedia dysfunction (PPID). Definitive diagnosis is made by measuring blood endogenous ACTH concentration... read more Hypertrichosis Associated with Adenomas of the Pars Intermedia (PPID) and EMS can occur concurrently in middle-aged and older horses. Horses with EMS should therefore be monitored to detect the onset of PPID. Alternatively, any horse with PPID should also be tested for insulin dysregulation. Horses with just PPID and not EMS rarely develop laminitis.

Clinical Findings of Equine Metabolic Syndrome

No clinical picture is pathognomonic for insulin dysregulation. Horses may exhibit all the phenotypic characteristics of EMS but have normal responses to evocative testing. In such instances, the animals in question are obese because of excess calorie intake rather than any underlying metabolic alteration.

Horses with EMS typically are obese, with a body condition score of > 6 out of 9. Even if the overall condition score is not extremely high, there is increased fat deposition in the neck, leading to a cresty appearance. Fat deposition over the ribs and over the topline to the tailhead is also common.

Geldings may have increased fat deposition in the prepuce; mares may have increased fat deposition around the mammary glands.

Laminitis is a common finding in cases of EMS. 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 or pedal osteitis.

Laminitis may occur secondary to the ingestion of feeds high in soluble carbohydrates, in the form of either lush pasture or high-carbohydrate hays and supplements. As a result, bouts of laminitis may develop 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 with EMS appear to have increased appetites and often will eat continuously, as long as feed is available. Mares affected with EMS show infertility and abnormal reproductive cycles.

Lesions

Increased general adiposity and laminitis are often documented in EMS cases.

The pituitary gland is normal in younger horses with EMS; however, lesions consistent with PPID may be found in older horses that are concurrently affected by EMS and PPID.

Diagnosis of Equine Metabolic Syndrome

  • Tests to confirm insulin dysregulation and exclude PPID

Diagnostic testing for EMS should concentrate on documenting insulin dysregulation while excluding 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 assessment of the patient's response to treatment for EMS. Even if there is no history of laminitis, careful examination of the feet, including lateromedial radiographs of P3, is indicated.

Because many factors, including diet, pain, and stress, can affect blood glucose and insulin concentrations, diagnostic testing for EMS 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 increased with EMS. If persistent hyperglycemia is documented, concurrent PPID should be strongly suspected.

Because many factors influence blood glucose and insulin concentrations, a onetime blood insulin measurement should be used only as a screening test for insulin dysregulation.

Insulin concentration should be determined after the horse has been fasted for 6–8 hours. This fasting regimen can be accomplished 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 mcU/mL suggests insulin dysregulation.

To document insulin dysregulation, the patient's physiologic response to glucose should be evaluated. Because some horses with EMS are normal in all respects except the ability to handle an oral carbohydrate load, an oral sugar test (OST) or oral glucose test (OGT) should be performed.

The OST is easy to perform in North America, where corn syrup is readily available; the OGT can be performed in other parts of the world.

  • The OST is performed by fasting the horse for 3–12 hours and then administering an oral dose of corn syrup at 0.15–0.45 mL/kg. Blood should be collected at 60 or 90 minutes after administration of the corn syrup to determine the insulin concentration. A concentration > 60 mcU/mL is abnormal.

  • The OGT is performed by giving a fasted horse 0.5 kg of chaff-based feed to which dextrose powder at 1 g/kg has been added. An insulin concentration > 87 mcU/mL in a blood sample collected 2 hours later is abnormal.

To assess whether an equid can metabolize its current diet appropriately, a baseline insulin concentration can be measured while the animal is on pasture. While having free access to pasture, the animal should be given no grain for at least 4 hours before testing. An increased blood insulin concentration (> 20 mcU/mL) indicates an exaggerated response to the animal's current diet.

To determine whether insulin can stimulate normal glucose uptake by peripheral tissues, an insulin tolerance test can be performed as follows:

  • A baseline blood sample is collected to measure glucose concentration.

  • Regular human recombinant insulin is administered at 0.1 IU/kg, IV.

  • A second blood sample is collected to measure for glucose concentration 30 minutes later.

In the second sample, a glucose concentration > 50% of the baseline valueindicates that the patient has insulin dysregulation.

Other diagnostic testing includes the IV glucose tolerance test and a combined glucose-insulin response test.

The oral glucose tolerance test can be altered by delayed gastric emptying or poor GI absorption, and it is less desirable than the combined 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 handheld glucometer may be used to determine blood glucose concentrations in these tests.

Tests for PPID, such as measuring endogenous ACTH concentration or thyroid-releasing hormone response, are normal in horses with EMS. Abnormal results (ie, increased concentrations of these hormones) indicate that the horse is concurrently affected by EMS and PPID, which can occur in older horses.

Detection of PPID is important because PPID is thought to exacerbate insulin dysregulation in horses also affected by EMS.

Treatment of Equine Metabolic Syndrome

  • Dietary management

  • Increased exercise

  • Thyroxine or metformin if diet and exercise adjustment is insufficient

Treatment for EMS involves dietary management and, if adjustment of diet and exercise is not sufficient to treat the condition, medical therapy. Dietary correction may be all that is needed to return the horse to normal body weight.

Dietary carbohydrate restriction is essential to decrease the glycemic and insulinemic response. Total calorie intake is restricted to decrease body weight.

The nutrient composition of a pasture can change hour to hour, and many horses with severe EMS cannot graze at all without experiencing laminitis flare-ups. For this reason, pasture access should be eliminated or severely restricted until body weight is in the desired range. Use of a grazing muzzle may aid in decreasing pasture ingestion.

The nonstructural carbohydrate (NSC) content of forage should be determined by feed analysis. NSC content can be calculated by adding together starch and water-soluble carbohydrate percentages. Ideally, NSC should comprise < 10% of the hay dry matter, and it should never exceed 16%.

Soaking hay in water for 60 minutes has been recommended to lower water-soluble carbohydrate concentrations. However, the actual amount of the decrease is extremely variable; therefore, soaking is not a reliable method to produce a low-NSC forage. It is particularly important to give a mineral supplement to animals fed soaked hay, because minerals leach out in the water along with the soluble carbohydrates.

Supplements should be given to provide needed vitamins and minerals but not additional calories. Complete feeds that are formulated to be low in digestible energy and carbohydrate and specifically designed for horses with insulin dysregulation may be provided 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 every 24 hours. This amount can be lowered to 1.25% and then to 1% 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 dysregulation.

Increasing the amount and intensity of exercise will increase the rate of weight loss. Five exercise sessions of 20 minutes or longer will increase insulin sensitivity. In horses with laminitis, walking as their comfort allows may be of some benefit.

Weight loss should be documented by scale measurement or weight tapes. In addition, neck thickness and diameter can be monitored over time. If increased exercise and dietary modification are not sufficient to decrease body weight, medical therapy may be of benefit.

Thin horses with EMS should receive increased calories in the form of roughage and fat. Molasses-free beet pulp, top dressing with vegetable oils, and low-carbohydrate, high-fat supplements can be fed until a desired body condition score is reached.

The thyroid hormone thyroxine, in the form of levothyroxine sodium, will accelerate weight loss and thereby improve insulin sensitivity when combined with dietary intervention in horses. Horses weighing > 450 kg can be administered 48 mg/horse, PO, every 24 hours; smaller horses and ponies should receive 24 mg/horse, PO, every 24 hours.

Treatment periods of 3–6 months are often needed to achieve desirable weight loss in EMS cases. When the weight loss has been achieved, the horse should be weaned off the medication over 3–4 weeks. If feed intake is not limited concurrently, treatment with levothyroxine is unlikely to resolve clinical signs. Access to feed and pasture should be limited because levothyroxine causes polyphagia in horses.

Metformin is poorly absorbed in equids; however, it may decrease postprandial glucose and insulin concentrations. It may lead to improvement in hyperinsulinemic horses at a dosage of 30 mg/kg, PO, every 8 hours. It should be administered 30 minutes before a meal, if possible. However, the longterm efficacy and safety of metformin has not been established in horses. If it is used, blood glucose should be carefully monitored. Metformin should be discontinued if hypoglycemia is documented.

Prevention of Equine Metabolic Syndrome

Prevention of EMS should focus on maintaining normal weight in horses, particularly in high-risk breeds.

Because horses with EMS may use ingested calories more efficiently than do other horses, it is imperative to feed appropriately to maintain an ideal condition score and not to use arbitrary feeding guidelines.

Particular care should be exercised when turning horses on pasture during times of high-soluble carbohydrate content (eg, spring and fall). Horses with EMS almost always require severe grazing restriction.

Key Points

  • The inability to metabolize carbohydrates, also known as insulin dysregulation, is the key problem in horses with EMS.

  • High blood insulin concentrations lead to laminitis, which can lead to devastating lameness, loss of use, and death.

  • In EMS management and prevention, it is important to feed an amount that maintains a normal body condition for each individual horse.

  • Many horses with EMS gain fat and develop laminitis when placed on pasture. Dietary management (ie, feeding low-carbohydrate hay) is important to prevent bouts of laminitis.

For More Information

References

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