Insulin Resistance and Equine Metabolic Syndrome

Equine Metabolic Syndrome (EMS) is a recently described collection of clinical abnormalities which shares some characteristics with PPID. Both of these disorders alter cortisol metabolism. EMS has no underlying connection to thyroid gland dysfunction. It is thought that EMS results from excess production of active cortisol primarily in fat cells, or adipose tissue. The pituitary gland functions normally in patients with this disorder.  Understandably, while the underlying causes of EMS and PPID may be different, the resulting clinical problems are very similar, including abnormal fat deposition (along the crest, over the tail head, and in geldings’ sheaths) and laminitis. EMS is typically seen in middle-aged horses, perhaps starting at 10-20 years of age. It is also observed more often in various breeds: pony breeds, domesticated Spanish mustangs, Peruvian Pasos, Paso Finos, Andalusians, European Warmbloods, American Saddlebreds, and Morgan horses. This suggests an EMS genetic predisposition is present, but this has not been scientifically proven.

With more recent study of the syndrome, experts agree that the term EMS should be used only when the following, three diagnostic criteria are met:

1. insulin resistance (IR);
2. history of or active laminitis; and
3. excess fat depositions in typical regions, i.e. neck crest, fat pads at the base of tail.

Insulin resistance is a term used to describe the condition in which various body tissues fail to respond appropriately to insulin. In a classic scenario, the individual has both abnormally high blood sugar and blood insulin concentrations. Once the pathologic state of IR develops, poor utilization of glucose from the diet and intermittent high blood sugar occurs (similar to Type 2 diabetes mellitus in people). Diets that are higher in carbohydrates exacerbate this state because they stimulate further insulin production when eaten. The possible mechanisms behind IR in horses are numerous and can be discussed with your veterinarian. A major concern with IR is that it appears to be linked to pasture-associated laminitis in horses and ponies. Thus, when IR is identified or suspected in a horse, veterinarians often suggest methods which may help a horse’s insulin sensitivity. This typically includes diet changes and an increase in regular exercise. As an aside, although IR is not identified in all horses with PPID, it can be an associated endocrine problem for many equine PPID cases as well.

 More recent research in horses with EMS has found that horses can have some of the same medical problems as people with metabolic syndrome. This may include:
– hyperglycemia
– altered tissue-level cortisol activity
– increased leptin concentrations
– altered lipid metabolism with hypertriglyceridemia
– increased expression of inflammatory cytokines
– hypertension
EMS – Diagnostic Test Options

For EMS, testing options are still debated as the equine medical community learns more about this syndrome. To diagnose EMS, presence of the previously described clinical changes and blood tests are used.  A single test to identify increased cortisol in fat tissue does not yet exist. The primary and most consistent laboratory abnormality is a high serum insulin concentration. In addition, because of the shared traits of animals with EMS and PPID, it is important to rule out a diagnosis of PPID. A distinguishing feature between EMS and PPID is the result of an overnight dexamethasone suppression test. EMS patients have normal responses, i.e. normal cortisol suppression following a dose of dexamethasone, whereas PPID patients have abnormal DST results, i.e. lack of cortisol suppression. Similarly, endogenous plasma ACTH concentration is normal in EMS cases and elevated in most PPID patients. Also, because laminitis is often the first complaint, assessing coffin bone position with foot radiographs is very important.

In addition, in order to evaluate a horse or pony for IR, it is recommended to measure the horse’s resting insulin concentration as well as perform an insulin-glucose sensitivity test. This test requires several blood samples to be collected over a relatively short period of time. It can be done in the field, but is often not practical for the busy, ambulatory veterinarian. Two test options are the IV glucose tolerance test (IVGTT) or the combined glucose-insulin test (CGIT). One can discuss the advantages and disadvantages of each test with a veterinarian.

When multiple sample tests are not performed, many veterinarians are using their test of choice for PPID combined with serum glucose and serum insulin measurements to evaluate a horse or pony for EMS. While the results can be frustrating and not point to an obvious diagnosis, they are still useful tools.  Veterinarians recognize that many horses and ponies fit an “inconclusive” category where PPID or EMS cannot be diagnosed with certainty. That said, it is often suggested to repeat diagnostic tests in horses suspected of having PPID or EMS. It is possible that at certain times, the subject’s hormone levels are abnormal, and at other times, they are normal.

EMS – Management Practices

Management of horses and ponies with EMS focuses on therapy for laminitis and dietary adjustments with the aim of limiting the stimulus for insulin production. Unfortunately, because of the abundance of high carbohydrate-content commercial feed options, diet supervision can be extremely difficult for owners. In order to decrease this stimulus for insulin secretion, an alternate feeding regimen with a low glycemic index is recommended for these patients.  Fortunately, this goal is becoming easier to achieve in today’s world.

Glycemic index signifies the degree to which a certain food raises blood sugar and insulin levels in the body. Molasses-based diets, such as sweet and certain senior feeds, oats, and barley have high glycemic indexes. Low glycemic index feeds include Bermuda grass hay, rice bran, and beet pulp. Other hays, such as timothy and alfalfa, have moderate glycemic indexes. An important recommendation is to feed grass hay or other feed sources which are low in water-soluble carbohydrates (WSC) or non-structural carbohydrates (NSC). Forage analysis of your hay is strongly encouraged to accurately determine the WSC/NSC content of one’s hay. NSC content below 12% is suggested for IR horses and ponies, in both EMS and PPID patients. Also, if more calories are needed, fat sources, such as vegetable oil or rice bran, are excellent choices instead of grains and feeds with high molasses content. Higher fiber content in the daily diet is also encouraged. This can be found in beet pulp and many commercially produced pelleted feeds.

Regarding medical therapy, some veterinarians have begun to look at use of trilostane (described in the PPID treatment section) in EMS cases. Again, this is an off-label use of the drug, but researchers argue that decreasing cortisol production by the adrenal glands may help reduce clinical signs in EMS patients.  Addition of oral antioxidants, Vitamin E specifically, has also been recommended (5000-7000 units per day). Before making any treatment decisions, additional therapy or supplement use should always be discussed with your regular veterinarian. Also, with any PPID and EMS patient, regular health check-ups are critical to long-term care. This includes the performance of basic blood work, dental care and regular foot/hoof trimming and care.

As said previously, chronic laminitis is the primary, day-to-day effect of EMS – and also the most life-threatening, if not controlled.  As with PPID-affected horses and ponies, making a team of people to manage EMS-associated laminitis is critical. Owners must maintain strict control of dietary management and be prepared for acute laminitis episodes during season changes (especially spring pasture) and any disruption to his/her horse’s typical daily diet. Managing a horse or pony with EMS requires a long-term commitment, but can be very successful.
By Emily A. Graves VMD, MS, Dipl. ACVIM

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