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Understanding the connection between Dysbiosis, Metabolic Disorder/IR and Systematic Inflammation and how to treat the equine to restore health

Part 2

by John J. Hanover, DVM

As already discussed, Insulin is a major regulatory hormone in glucose and fat metabolism, vascular function, inflammation, tissue remodeling, and growth. Insulin is secreted by the pancreas to stimulate the uptake of glucose by tissues when sugar is abundant, such as after eating. The tissues most responsive to insulin-mediated glucose uptake are skeletal muscle, adipose cells, and the liver. Insulin resistance (IR) is defined as the failure of tissues to respond appropriately to insulin. In human medicine, insulin resistance has been implicated in reducing glucose availability to insulin-sensitive cells, vasoconstriction, endothelial damage, and inflammation. In equine laminitis, we see these changes and reactions occurring within the hoof wall. Some practitioners are using the term Equine Metabolic Syndrome to indicate when a horse is insulin resistant, has a history of laminitis, and abnormal fat deposits or a cresty neck.
Horses with Equine Cushing’s, or Pituitary Pars Intermedia Dysfunction (PPID), can present similar to IR horses as they often have cresty necks, abnormal fat pads, and a history of laminitis. On lab work, they may also have elevated fasting insulin levels, elevated glucose and low thyroid levels. One of the classical distinctions for Equine Cushing’s is the long curly hair coat (hirsutism). In fact, hirsutism is pathognomonic for PPID in older horse and has been used as the gold standard for diagnosing the disease. Early evidence of hirsutism includes retention of the winter haircoat for longer than expected or detection of longer hairs on the palmar or plantar aspects of the lower leg. Affected horses are usually older (>15 years), have a thick cresty neck, may be overweight and have bulging supraorbital fat pads, may be PU/PD and hyperglycemic, and have a history of chronic infections, delayed wound healing and/or multiple injuries.

The simplest and least expensive way to test a horse for IR is to measure resting serum insulin levels. A blood sample should be obtained after fasting at least 4 hours or eating only grass hay. Stress needs to be avoided to prevent false positive results. This is a useful screen, but may indicate a false negative in horses with early or mild IR where the horse’s insulin level may fall into the high normal range.

Another test for IR is the combined glucose-insulin test which requires collecting multiple blood samples and administering a dextrose solution followed by an infusion of insulin. This test takes more time, involves a slight risk of hypoglycemia, and is more expensive. Stress and pain, such as from laminitis, can alter the test results.

To diagnose Equine Cushing’s or PPID, the horse’s age, history and clinical appearance should be taken into account with any and all blood work results. There are many different tests being used to diagnose Equine Cushing’s and all of them have false positive and false negative rates that vary with to the stage of the disease, stress, excitement, pain, and even the month or season of the testing. For example, one study using the ACTH concentration test had a >90% false positive rate in ponies and horses residing in Pennsylvania during the month of September.1 The different testing options for Equine Cushing’s includes: Oral Domperidone Test (ODT), Dexamethasone Suppression test (DST), Thyrotropin-Releasing Hormone (TRH) test, a combined DST/TRH test, Diurnal Cortisol Rhythm test, and ACTH Stimulation test . For more information and protocols on these tests, please refer to the Guide to Insulin Resistance & Laminitis for Equine Practitioners, copyrighted by LLOYD Inc. (800-831-0004).

In my practice, I test all suspected cases of EMS and PPID by collecting two serum samples in one day 8 to 10 hours apart. The animal should be maintained in its normal environment if possible to reduce stress as that can alter results. No grain or treats should be given within 4 hours of either sample. The morning sample is collected first and the second sample 8 to 10 hours later. Both samples are assayed for cortisol, thyroxine (TT4) and insulin at BET Labs in Kentucky (859-273-3036). The absolute values of cortisol will usually be between 20 - 90 ng/ml. However, we are calculating the change in cortisol values between the two samples. The normal horse has a value greater than 30% between the two samples. The false positive rate for this test is about 30% since some normal horses will test positive due to stress or other unknown factors. The false negative rate is extremely low. If phenotypic changes are present such as hirsutism, chronic endometritis, chronic laminitis and obesity, and their cortisol rhythm is less than 30%; our experience has found that animals will respond clinically to appropriate therapies.

Managing horses with IR, EMS, and/or PPID (Cushing’s) share many common treatment principles. These include an appropriate diet and exercise program to increase insulin utilization, reduce or prevent obesity, and decrease the risk of laminitis. If any of these horses are truly hypothyroid or if they are obese, treatment with levothyroxine (Thyro -L) may be beneficial. Overweight horses placed on Thyro-L showed an increased weight loss and improved insulin sensitivity as they lost weight. It is important that the owners realize that the horse may have an increased appetite and eat more if their diet is not controlled. Research published in Veterinary Immunology and Immunopathology in January 2009 showed that as overweight horses lost body fat, their levels of inflammatory cytokines dropped steadily. It was also demonstrated that as the horses picked up weight again, the cytokine levels came back up creating a systemic pro-inflammatory state.

Horses with IR, EMS, and/or PPID often respond well to supplements containing chromium, magnesium, cinnamon, and other ingredients used to support insulin’s actions, maintain normal glucose levels, and improve endocrine function. Chromium is known to improve the efficiency of insulin at the cellular level transporting glucose from blood into the cells. I routinely use Equine X-Formula from KAM Animal Services for all these cases at a starting dose of 2 tablespoons twice a day and up to three times a day for horses in a crisis such as acute laminitis. Some horses will respond to the diet changes, increased exercise (weight reduction if overweight) and Equine X-Formula without any other medical treatments. If the horse does not respond well enough clinically to this treatment or the lab values are still poor or there is laminitis, I will add other medical therapies. In all of these cases, I will discuss and recommend a gastrointestinal conditioning program and a minimal vaccination schedule. Ulcers and ‘leaky gut syndrome’ can greatly increase the risk of laminitis and complicate the treatment of laminitis while creating a systemic pro-inflammatory state.

There are three drugs currently used in the US to treat PPID, but pergolide is the treatment of choice at this time. Pergolide is a dopaminergic agonist that inhibits the activity of the pars intermedia and may slow the progression of PPID. Cyproheptadine was the most common treatment before Pergolide and is still used alone or in conjunction with Pergolide quite often. Cyproheptadine inhibits the action of serotonin, an excitatory neurotransmitter, to reduce activity of the pars Intermedia. Trilostane is available from Canada and Europe for import with special FDA approval. Trilostane works by inhibiting an enzyme at the adrenal cortex that is involved in cortisol production.

Obviously, horses with laminitis should be receiving appropriate trimming and treatments, allopathic and holistic, specifically for the laminitis. As endocrine diseases and gastrointestinal disorders are the most common causes of laminitis, they should be tested for and/or treated in all cases of laminitis without another known cause or trigger.

There are a number of diseases or conditions with many different names that result in very similar health problems clinically. Whether we call it Inflammatory Bowel Disease (IBD), Dysbiosis, Leak Gut Syndrome, Hindgut Acidosis, Equine Gastric Ulcer Syndrome (EGUS), colitis, or any other term for a break down in the health of the gastrointestinal tract, the resulting pathophysiology can be devastating to the health of our patients. This is a very common problem in our horse population. In one study, a group of 180 performance horses (race and show) were necropsied. Of these, 87% had gastric ulcers, 63% had colonic ulcers, and 54% had both gastric and colonic ulcers. Overall, of the 180 horses, 97% had ulcers in the GI tract. 2

Keep in mind that the gastrointestinal tract is the first line of defense to keep pathogens and toxins from entering the body. As the GI tract is so important for protecting the body, around 70% of the body’s entire immune system is located in the GI tract. When there is a break down in the integrity of this barrier, a whole cascade of physiological effects is triggered throughout the body. As pathogens and/or toxins enter the body through the GI tract an immune response is triggered by the MALT and GALT. The increase in active immune tissues and resulting up regulation of immune factors creates a pro-inflammatory state throughout the body. The circulatory system then transports the ‘invaders’ to the liver for processing and detoxification. Once the liver’s pathways become overloaded, the body will mobilize the toxins to other tissues in an effort to destroy or neutralize them. As the skin shares similar detoxification pathways as the liver, the body will deposit these toxins in the skin. This explains all the chronic skin and ear problems we see in practice secondary to GI problems. Now that the body is in a pro-inflammatory state and all these extra toxins are circulating, when a soft tissue injury occurs the body is unable to efficiently heal the tissue and resolve the issue. For example, a minor fetlock sprain that should have healed in a couple of weeks may become active chronic synovitis and eventually result in traumatic arthritis. Add the complications of metabolic disorders in these horses with GI problems and we can see why so many of them have chronic inflammatory diseases such as myositis, synovitis, COPD, hives, laminitis, and so on.

Treatment of these horses from an allopathic approach uses a variety of medications depending on the presentation of the horse. The inflammation or pain may be suppressed with NSAIDS (bute, Banamine, Naproxen, Ketofen, and Equioxx). The horses with muscle spasms may be given methocarbamol to depress the CNS. If allergy symptoms appear in the airways or skin, steroids are often used to suppress the immune system. Many of these medications have multiple possible side effects, including GI ulceration, liver and kidney toxicity. The stomach ulcers may be treated with Gastrogard or omeprazole. GastroGard is FDA approved to treat gastric ulcers and does so by inhibiting gastric acid pumps. GastroGard does not address colonic ulcers nor does it address the causes of ulcerations. So often, the allopathic medical treatments for the horses’ inflammation worsen the gastrointestinal tracts’ problems thereby increasing the risk of laminitis and creating an even stronger systemic pro-inflammatory state.

My treatment for gastrointestinal tract diseases and the secondary complications involves a multi-pronged approach. The first step is to remove or prevent the toxins, parasites, drugs, stress, and/or pathological processes that are causing the GI inflammation or ulceration. The next step is to feed an appropriate diet in a way to improve digestion and support GI health. This would usually tend toward free choice grass hay and “grain” , if any “grain” is fed, being given in multiple small feedings to decrease GI tract acidosis and lower the glycemic response to the “grain”. The third step is to improve digestion and aid the GI tract in healing. I often use KLPP from KAM Animal Services as my probiotic of choice as it contains Saccharomyces boulardii in a liquid formula that helps reduce GI acidosis and promotes ‘friendly’ bacteria. A study published in JAVMA 2005 supported the use of Saccharomyces boulardii, a nonpathogenic yeast, to decrease the severity and duration of diarrhea in horses. Other research has shown adding beneficial yeast to diets of horses can: stimulate & stabilize microbial activity in the hind gut, reduce incidence of colic and GI ulceration by maintaining pH balance through colonization of healthy microbes reducing ‘hind gut acidosis, improve digestibility and utilization of multiple nutrients, and improve hoof, skin and coat quality. Horses with known ulcers or that don’t respond to my initial treatment are given UF Formula from KAM along with the KLPP. I use the homotoxicology medication, Mucosa compositum from Heel to help repair the GI tract. Additionally, I frequently add digestive enzymes to the horses’ meals. The next steps are to balance the immune system, support and detoxify the liver, and treat any symptoms or pathology present. I use mostly Heel products and some Guna products to accomplish these goals. Traumeel induces an immunological bystander reaction which activates regulatory lymphocytes acting as an anti-inflammatory agent and immunomodulator. Hepar compositum is useful for aiding the GI tract and the liver. Heel’s Detox kit contains Lymphomyosot, Nux vomica-Homaccord, and Berberis-Homaccord. The Detox kit helps mobilize and drain toxins thru the lymphatics and supports toxin excretion thru the liver, GI tract and kidneys. There are a number of medications for cellular activation support (Coenzyme compositum and Ubichinon compositum) and products for specific tissues and organ systems available from Heel and Guna. Herbs can also be used to aid in detoxification and organ support.

1. Donaldson MT, McDonnell SM, Schanbacher BJ, et al. Variation in plasma ACTH concentration and dexamethasone suppression test results with season, age and sex in healthy ponies and horses. J Vet Int Med 2004;19:217–221.
2. Journal of Eq Vet Science, March 2005, Results of a Large-Scale Necroscopic Study on Equine Colonic Ulcers