This is a complicated topic, and this review is directed to veterinarians, vet students, veterinary nurses, and nursing students. However, many owners will hopefully find the article informative and helpful in understanding this complicated but common syndrome.
Most of us are familiar with the terms Metabolic Syndrome (MetS), obesity, insulin resistance (IR) and type II diabetes in human medicine. In the early 2000’s Phillip Johnson introduced the term Equine Metabolic Syndrome, to describe a syndrome of obesity, insulin resistance and laminitis in horses and ponies. There are many similarities shared between Equine Metabolic Syndrome (EMS), Fat Cow Syndrome (FCS), and Human Metabolic Syndrome (MetS).
Insulin resistance (IR) is at the heart of EMS, with a compensatory or independent increase in serum insulin concentration. Insulin is produced by the beta cells of the pancreas in response to glucose in the circulation. The key function of insulin is to bind to the surface of cells initiating a sequence of events that results in presentation of glucose transport proteins, such as GLUT4, at the cell surface. This allows glucose to enter the cells, where it can be used to make glycogen or fatty acids. Insulin resistance is the failure of tissues to respond normally – the precise cause is not known, but could involve a decrease in insulin receptors on the cell surface, malfunctioning of these receptors, affected cellular signalling pathways or failure to present GLUT4 transport at the cell surface. In equine medicine the term insulin dysregulation (ID) was introduced as a more over-arching term, representing EMS rather than simply insulin resistance.
Obesity is a feature of many cases of EMS, but it is not always present. Likewise, not all obese horses have insulin dysregulation. Other features of EMS include increased blood pressure with a secondary increase in cardiac dimensions, increased resting heart rate, and decreased concentrations of adiponectin and increased leptin concentrations. Adiponectin is a fat-derived hormone that protects against insulin resistance. Horses with EMS are likely in a chronic systemic inflammatory state, and concentrations of inflammatory cytokines are elevated in the lamellar tissues of feet in horses with hyperinsulinaemia.
Laminitis is the primary clinical consequence of EMS. Epidemiological studies have identified the following factors as risk factors for laminitis: low adiponectin, high insulin, elevated body condition scores (BCS), and generalized or localized adiposity. Experimentally high levels of insulin can induce laminitis.
Affected animals are at risk of hyperglycaemia and hyperlipidaemia.
There is a genetic predisposition to EMS. Breeds most commonly affected with EMS include all ponies, Morgans, Paso Finos and Peruvian Pasos, and Norwegian Fjords. Other breeds that have been diagnosed with EMS include Quarter Horses, Tennessee Walking Horses, Arabians, Thoroughbreds, and Warmbloods. Many of these breeds have been well adapted to survive and thrive in conditions of poor quality forage.
The triggers for these susceptible animals are:
- Grazing of lush pasture, usually in spring. These pastures are rich in sugars and hydrolysable carbohydrates and lead to obesity even when pasture is the only feed source available.
- Feeding of concentrate feeds that are rich in starch and simple sugars is an unnatural practice for susceptible animals. The post-prandial surge in blood glucose (and insulin, post-prandial hyperinsulinaemia) is difficult for these animals to manage because of their tissue resistance to insulin.
- Interference with normal seasonal weight loss. Susceptible breeds under ‘natural’ conditions would normally lose weight over the colder months of winter. Owners feel compelled to interfere with this expected loss by supplementing feed during this time. The winter weight loss is thought to be a natural correction period for animals with insulin resistance.
Most affected animals are 10 – 20 years of age, although younger animals can be affected. Given the age of onset, it is possible that Pars pituitary intermedia dysfunction (PPID) can complicate the management of EMS, and vice versa.
Signs of EMS
The principle lesion in EMS is laminitis. There is a strong association between the onset of laminitis and access to lush, sugar rich spring pasture.
Most, but not all, horses have generalized or regional adiposity. There may be a cresty neck, with focal fat deposits around the supraorbital fossa, behind the shoulder, the tailhead and the sheath in male horses. Almost universally, these horses and ponies are described as ‘easy keepers‘. Increased adiposity generally occurs before laminitis.
It is reported that affected mares may be infertile, despite cycling normally.
Diagnosis
The diagnosis is strongly suspected on the basis of history, physical examination and clinical signs.
There are several laboratory-based tests that are important in understanding whether there is insulin dysregulation, and if so, what is the magnitude of the problem. It is important to remember that this is not an all or nothing disease, therefore there will be horses that fall into the ‘grey zone’ in these tests.
Insulin can be measured using different laboratory techniques, radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), or chemiluminescence immunoassay (CLIA). The variability between techniques is relatively great, so it is important to use a constant method for clinical samples. The CLIA method yields insulin results that are significantly lower than the other 2 methods. RIA yields a higher result than ELISA, but this was not significant. The results may be reported as μU/ml or mU/L, the numeric value is identical for both units. Less commonly the value could be reported as pmol/L, which is actually the recommended si unit. To convert μU/ml or mU/L to pmol/L multiply the value by 6.9444. To convert pmol/L to μU/ml or mU/L multiply the value by 0.144. The numbers in this review were primarily determined using RIA.
The simplest test is to perform a baseline measurement of insulin. Horses with moderate to severe insulin resistance will have higher resting levels of insulin, to compensate for the tissue failure of the hormone. There are some important limitations with this test. The horse should not have received any form of concentrate in the 4 hours prior to sampling, and the horse should not be on pasture, but rather fed a low sugar pasture hay. Avoid using this method when there is active laminitis, as pain can alter insulin sensitivity. A positive test would be an insulin concentration greater than 30 μU/ml. If the animal was fasted then values greater than 20 μU/ml are suggestive of insulin dysregulation. Values greater than 100 μU/ml is classified as severe hyperinsulinaemia with a high risk risk for laminitis.
A more accurate test is the in-feed glucose test or the oral sugar test. The basis of these tests is to measure the rise in insulin after receiving an intestinal glucose load. Horses with insulin resistance will have an exaggerated insulin response to an oral glucose challenge. These tests presume that the small intestine is free of disease. Intragastric glucose is used to evaluate gastric emptying and small intestinal absorption. It is important that the horses are not starved for long before testing (starving reduces the tissue sensitivity to insulin). Ideally, they should be stalled and a receive one flake (biscuit) of a low sugar hay during the night prior to testing the following morning.
The oral sugar test is very popular in the US. It uses Karo Light corn syrup and is given using a dosing syringe at a dose rate of 0.15 mL/kg bodyweight. This provides 150 mg/kg of dextrose-derived sugars. A blood sample is drawn 60 – 90 minutes after dosing and glucose and insulin are measured. A positive response is a serum insulin concentration >60 μU/ml and blood glucose > 6.4 mmol/L (115 mg/dL). Horses with an insulin concentration <45 μU/ml are considered normal, and values between 45 and 60 μU/ml are equivocal. It is recommended to re-test the equivocal cases using 0.45 mL/kg of Karo Light syrup. The syrup is available in Australia at the usafoods website.
The in-feed glucose test utilizes dextrose powder. Horses should receive 0.5 kg to 1.0 grams/ kg bodyweight, mixed with a handful of chaff. Ideally the chaff is low in non-structured carbohydrates. A blood sample is taken at 2 hours after the meal is finished. Insulin dysregulation is confirmed if the serum insulin concentration >56 μU/ml for 0.5 gm/kg dosing, or >86 μU/ml after 1.0 gm/kg dextrose.
Treatment
Insulin sensitivity can be positively manipulated through management and medication.
Weight reduction can significantly improve insulin sensitivity and reduce basal and stimulated insulin levels. This is critical for the obese horse and is through a combination feeding and exercise. There is evidence that exercise improves insulin sensitivity and reduces appetite. The biggest obstruction to exercise is laminitis.
The laminitis needs attention working closely with a farrier and veterinarian. It is should be a slow process of realignment of the rotated third phalanx (P3) through trimming the toe and raising the heel, done in stages. Radiographs are very important. Laminitis is a devastating condition. One small ‘positive’ is that changes with endocrinopathic laminitis are almost always P3 rotation, and rarely involve ‘sinking’ or distal displacement of P3. P3 sinking is extremely difficult to manage.
Feeding is key, focusing on limiting soluble or non-structural carbohydrates (NSC). In an ideal situation pasture and hay should be less than 10% NSC. If the hay cannot measured then soaking for 30 minutes in cold water will reduce the sugar content. The hay should be covered by the water and fed soon after to limit mold growth. Hay steaming for an hour is primarily used to improve palatability and reduce dust and mold. It does also significantly reduce the NSC content (by around 3%), but not as much as soaking in cold water. Steaming may be preferred because much of the other nutrients that are lost through soaking are keep intact.
Feeds that must be avoided include grains in any form, carrots, apples, molasses and fresh grass. Fat supplements should be avoided. Pasture access should be restricted in spring, with access for 1-2 hours in the morning only (between 5 am to 10 am) when the sugar content is lowest. The exception is to avoid access after a frost, as during cold temperatures the grasses do not utilize sugar for growth. The remainder of the time they should housed in a dry lot or have a grazing muzzle on.
It is important the this a slow controlled process. You should aim to feed around 1.25 – 1.5% of the ideal body weight.
Managing the lean horse with regional adiposity is more challenging. The following recommendations are from Dr Martha Mallicote at the University of Florida, an expert on EMS.
- Feed a diet consisting of hay (<12% NSC) , soaked molasses-free sugar beet pulp, balanced vitamin and mineral supplement and 0.5 cup rice bran oil or corn oil BID
- The same diet with a commercial low-starch specialty feed substituted for beet pulp
- Feed a pelleted feed designed for old horses
Medications and supplements
There are several medications that may be beneficial to horses or ponies with EMS. There are positive reports of feeding psyllium and chromium picolinate supplements.
Pharmaceutical agents that may improve insulin sensitivity or therefore lameness include:
- Levothyroxine – Weight loss can be accelerated and insulin sensitivity improved by administering levothyroxine sodium in the feed for 3-6 months. This is given at a supraphysiologic dose, but is safe when used for periods not exceeding 3-6 months. The horses should be weaned off the drug. This is not a chronic therapy.
- Metformin – Commonly used medication in humans. It acts by enhancing the action of insulin at a post-receptor level. Studies have indicated that it is poorly absorbed in horses, but other studies have indicated that the drug may work at the intestinal level and need not be absorbed to be effective.
- SGLT-2 inhibitors – There are a number of these drugs that have been used off-label in horses. These drugs have been shown to rapidly reduce insulin levels and likewise to rapidly improve lameness in most ponies with acute or chronic laminitis. There are concerns about a release of insulin-mediated suppression of lipolysis and therefore increased levels of triglycerides are expected with this class of drugs. Horses should also be monitored for evidence of secondary hepatic lipidosis.
Dosing
Dosing information is intended for use by registered veterinarians or veterinary nurses. Equiimed assumes no responsibility for the information detailed below. Equiimed shall not be liable for any damages resulting from reliance on any information provided below, or by reason of any misstatement or typographical errors. Ultimately veterinarians should consult information provided by the manufacturer prior to use.
Tags: Endocrine and Metabolic