Equine metabolic syndrome (EMS) is a characteristic collection of clinical signs and clinicopathological changes in equids that increases their risk for developing hyperinsulinemia-associated laminitis (HAL), the leading cause of laminitis. Insulin dysregulation (ID) is the core component of the syndrome; it is defined as any combination of resting hyperinsulinemia, postprandial or postchallenge hyperinsulinemia, and peripheral or hepatic insulin resistance.
EMS is found in both horses and ponies and has also been recognized in donkeys. Affected animals typically are obese, with increased body condition score overall and increased regional adiposity in the neck and tailhead regions (see generalized obesity image); however, a lean EMS phenotype is also described (see lean phenotype image).
Courtesy of Dr. François-René Bertin.
Courtesy of Dr. François-René Bertin.
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 Saddlebreds, Tennessee Walking Horses, Paso Finos, Morgans, and Mustangs.
It occurs infrequently in Thoroughbreds and Standardbreds; however, any horse can develop EMS.
Etiology and Pathogenesis of Equine Metabolic Syndrome
Equine metabolic syndrome develops because of a disturbance in the relationship between circulating glucose and insulin, leading to insulin dysregulation. The specific origin of ID is currently unknown and likely involves the combination of a diet inappropriately high in nonstructural carbohydrates and a favorable genetic background leading to hyperinsulinemia and insulin resistance.
Hyperinsulinemia results from excessive insulin secretion after ingestion of nonstructural carbohydrates and possibly from a decreased hepatic clearance of insulin, either as a primary event or as a compensation for insulin resistance. Insulin resistance is the inadequate response of insulin-sensitive tissues, either as a primary event or as a compensation for hyperinsulinemia.
Additional laboratory findings of EMS include hypertriglyceridemia, increased serum concentrations of leptin, and decreased concentrations of adiponectin, indicating that lipid metabolism is also altered in this condition.
Hyperinsulinemia leads to laminitis in horses and ponies, and HAL represents approximately 90% of the cases of laminitis in the general equine population. Although HAL can present as an acute episode of laminitis, it is often a chronic and recurring condition with repeated episodes of mild to severe lameness.
Pearls & Pitfalls
|
The histological findings of HAL differ from those of the other two types of laminitis (sepsis-associated laminitis and supporting-limb laminitis); they include narrowing, stretching, and elongation of the secondary epidermal lamellae associated with cellular proliferation of the secondary epidermal lamellae, infiltration of the dermis by leukocytes, and damage to the basement membrane. The pathogenesis of HAL is not clear but likely includes the stimulation of insulin-like growth factor 1 receptors (IGF-1Rs).
Although they are two different conditions, pituitary pars intermedia dysfunction (PPID) and EMS can occur concurrently in middle-aged and older horses in approximately 30% of cases. Therefore, when they reach the age of 12–15 years, horses with EMS should be monitored to detect the onset of PPID. Alternatively, any horse with PPID should be tested for ID. It is important to note that horses with just PPID, and not ID, rarely develop laminitis; therefore, if a horse with PPID develops laminitis, a diagnosis of ID is very likely.
Clinical Findings of Equine Metabolic Syndrome
No clinical picture is pathognomonic for equine metabolic syndrome.
Horses with EMS typically are obese or overconditioned, with a body condition score of ≥ 7 out of 9 and a cresty neck (see cresty neck image). However, regional adiposity with fat deposition behind the shoulder and the tailhead are common in horses with EMS even if generalized obesity is not present.
Courtesy of Dr. François-René Bertin.
Geldings with EMS might have increased fat deposition in the prepuce; mares might have increased fat deposition around the mammary glands and show infertility or irregular reproductive cycles.
Horses with EMS that are brought in for evaluation with no known 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 (see growth rings image).
Courtesy of Dr. François-René Bertin.
HAL might 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 often develop in the spring, when new pasture growth appears, and in autumn, when night temperatures are below freezing.
Lesions of Equine Metabolic Syndrome
Increased regional adiposity and laminitis are the most commonly documented lesions in EMS cases (see foot distortion image).
Courtesy of Dr. François-René Bertin.
The thyroid gland is invariably normal in horses with EMS, and the pituitary gland is normal in younger horses with EMS. Lesions consistent with PPID are found only in older horses that are concurrently affected by EMS and PPID.
Diagnosis of Equine Metabolic Syndrome
Tests to confirm insulin dysregulation
Diagnostic testing for equine metabolic syndrome should focus on documenting insulin dysregulation. Obesity and a cresty neck are not sufficient to make a diagnosis of EMS, and absence of obesity is not sufficient to exclude ID. A careful dietary history and physical examination are essential.
Establishing baseline body condition and neck scoring enables 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 radiography of the pedal bones, 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.
Blood glucose concentrations have no diagnostic value, because usually they are in the normal range or only slightly increased with EMS. If persistent hyperglycemia is documented, concurrent PPID should be strongly suspected.
A single blood insulin measurement should be used only as a screening test for ID; a high concentration indicates EMS, but a low concentration cannot exclude the disease.
Insulin concentration should be determined after the horse has been fasted for 3–6 hours. This fasting regimen can be accomplished by leaving only one flake of hay with the horse after 10 PM and then collecting a blood sample the next morning. If those conditions are met, a blood insulin concentration > 45 mcIU/mL is consistent with ID.
If the baseline insulin concentration is normal, the patient's physiological 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 performed by fasting the horse for 3–6 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 ≥ 45 mcIU/mL is consistent with ID.
The OGT is performed by giving a fasted horse 0.75 g/kg of dextrose powder mixed with chaff. An insulin concentration ≥ 65 mcIU/mL in a blood sample collected 2 hours later is consistent with ID.
The OST and the OGT correlate well with the risk of HAL and are useful diagnostic tests. To monitor a previously diagnosed case and to assess whether an equid can metabolize its current diet appropriately, a postprandial insulin concentration measurement 2 hours after feeding is recommended, whether the diet is hay or pasture.
A blood insulin concentration ≤ 50 mcIU/mL indicates an acceptable response to current management and a low risk of laminitis. A blood insulin concentration ≥ 100 mcIU/mL indicates inadequate management and a high risk of laminitis. At blood insulin concentrations between 50 and 100 mcIU/mL, the risk of laminitis is unclear.
Tests for PPID, such as measuring endogenous ACTH concentration at baseline or after thyroid-releasing hormone stimulation, are normal in horses with EMS. Abnormal results indicate that the horse is concurrently affected by EMS and PPID, as can occur in older horses.
Detection of PPID is important because PPID is thought to exacerbate ID in horses also affected by EMS.
Treatment of Equine Metabolic Syndrome
Dietary management
Farriery
Exercise
Pharmaceuticals
Diet is the most important element in the management of equine metabolic syndrome, and dietary adjustment is sufficient to manage most cases. For all patients with EMS, whether obese or not, grazing, grains, and treats should be eliminated. Hay that is low in nonstructural carbohydrates (10%, as determined by feed analysis) should be provided in a slow feeder or divided into multiple small meals (ideally, 4–6) for a daily total of 2% of body weight when the body condition score of the horse or pony is 5/9. In obese horses, the daily total can be decreased to 1.5% of body weight; however, severe restrictions can be detrimental and increase the risk of hyperlipemia. In any case the amount of non-structural carbohydrates should not exceed 0.1 g/kg per meal.
Other strategies for adjusting the diet to manage EMS include soaking hay for 60 minutes to decrease the nonstructural carbohydrate content and providing a low-sugar ration balancer or substituting high-quality straw.
The decision to allow grazing or change the diet of an EMS patient depends on the clinical signs (resolution of laminitis, body condition score) and on the postprandial insulin concentration. The nutrient composition of a pasture can change from hour to hour, and insulin responses should be monitored frequently, even in well-managed horses.
Numerous dietary supplements, including cinnamon, chromium, and magnesium, have been suggested to increase insulin regulation in horses with EMS. None of these supplements have been shown to improve insulin regulation in horses in experimental situations.
Hoof care by a skilled farrier is essential in all EMS cases, even in the absence of acute laminitis. HAL can occur without inducing obvious lameness, and radiography is recommended to detect hoof distortion. In at-risk cases, regular hoof trimming every 4 weeks by an experienced farrier is highly recommended.
If laminitis has resolved, exercise helps to improve insulin sensitivity by building muscle mass and decreasing fat mass. All levels of exercise are beneficial, and 5 minutes of walking followed by 15 minutes of brisk trotting followed by 5 minutes of walking 5 days a week improves insulin regulation. More exercise (eg, 30 minutes of cantering 5 days a week) can be added. While the intensity of exercise is being increased, it is paramount to ensure that the horse does not become lame.
No drug is currently labeled for managing insulin dysregulation in horses, and no drugs should be used without implementation of a proper diet.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promising results in managing hyperinsulinemia and HAL. These drugs can be used when dietary management fails and in cases of acute onset of HAL. In the absence of pharmacokinetic data, the doses of these drugs have been extrapolated from human medicine.
The following SGLT2 inhibitors, as needed, may be administered long-term, depending on clinical response:
velagliflozin: 0.3 mg/kg, PO, every 24 hours
canagliflozin: 0.2–0.6 mg/kg, PO, every 24 hours
ertugliflozin: 0.02–0.06 mg/kg, PO, every 24 hours
empagliflozin: 0.02–0.06 mg/kg, PO, every 24 hours
Although not approved for use in horses, these drugs are commonly administered extralabel. In some cases, severe hypertriglyceridemia is reported; however, the clinical relevance of these increases is unclear. The duration of treatment is also undetermined and likely variable, depending on clinical response.
The effect of metformin, an antidiabetic drug approved for humans, on equine insulin sensitivity has been variable, and this drug is poorly absorbed in horses. In some cases, however, insulin sensitivity has increased and insulin concentrations have decreased, indicating some possible effect. Metformin (30 mg/kg, PO, every 8–12 hours) is commonly administered 30 minutes before feeding; it may be used long-term, depending on clinical response.
Although horses with EMS do not suffer from hypothyroidism, levothyroxine sodium has been used to help with weight loss. Levothyroxine sodium is commonly administered at 48 mg/horse (or 24 mg/pony), PO, every 24 hours for 3–6 months or until the animal reaches a body condition of 5/9. The horse should be weaned off the medication over 3–4 weeks.
Trials of drugs such as pioglitazone or exenatide in horses have yielded variable results, and recommendations cannot yet be made.
Prevention of Equine Metabolic Syndrome
Prevention of equine metabolic syndrome should focus on providing an adequate diet and maintaining normal weight in horses, particularly in high-risk breeds.
Because horses with EMS use ingested calories more efficiently than do other horses, it is imperative to feed patients 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 autumn). Horses with EMS almost always require severe grazing restriction.
Key Points
Insulin dysregulation is the key problem in cases of equine metabolic syndrome.
High blood insulin concentrations lead to laminitis, which can result in 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.
Dietary management (ie, feeding low-carbohydrate hay) is important to prevent bouts of laminitis.
For More Information
EMS/ID Working Group. Recommendations for the Diagnosis and Management of Equine Metabolic Syndrome (EMS) and Insulin Dysregulation. Equine Endocrinology Group; 2024.
Bertin FR, de Laat MA. The diagnosis of equine insulin dysregulation. Equine Vet J. 2017;49(5):570-576.
Durham AE, Frank N, McGowan CM, et al. ECEIM consensus statement on equine metabolic syndrome. J Vet Intern Med. 2019;33(2):335-349.
Also see pet owner content regarding metabolic disorders in horses.
