Understanding Equine Insulin Resistance: Finding the Missing Pieces Through Science

October 12, 2023

By Sarah Griffiths, DCH

Everyone knows a horse with insulin resistance. It’s one of the most prevalent issues facing aging horses in the modern world. It’s also one of the most mysterious. Insulin resistance (IR), also known as equine metabolic syndrome (EMS), is defined as the failure of tissues to adequately respond to circulating insulin and keep blood sugar balanced.

Symptoms include:

  • Obesity with fat deposits in the neck, topline, ribs, tail head and above the eyes
  • High blood insulin
  • Normal blood glucose
  • Lethargy
  • PU/PD
  • Acute laminitis

This disease is still relatively misunderstood but if we go into the science with a dynamic way of thinking, we can find breadcrumbs.

In this article, I’ll compile some of the research on IR in equines and humans to better understand why so many horses are having trouble with this frustrating metabolic issue. I’ve pulled from human and pet research because many aspects of IR have not been explored in detail in horses but have in people and other animal species. It will help us to understand better what we can do to help our horses. We’ll discussion solutions in a second article (stay tuned!).

Healthy Insulin Metabolism

Due to its prevalence, IR has been well studied in horses. It has also been recognized as a preceding factor in the development of laminitis, a devastating inflammatory disease causing lameness and can even result in death. So where do things go wrong? In order to understand how to help IR horses, we need to understand how insulin metabolism works in a healthy horse.

Insulin is an endocrine hormone secreted largely from the pancreas. It acts as a key, unlocking a number of complex metabolic processes in the body. Here’s a step by-step breakdown of how it works:

  1. The pancreas (located in the abdomen) houses special (islet) cells that produce the hormone insulin. Cells throughout the body have special receptors that are genetically programmed to bind to insulin when they are functioning correctly (insulin-sensitive).
  2. The islet cells excrete insulin when glucose (sugar) increases in the bloodstream, typically after eating.  The more sugar in the bloodstream, the more insulin is released.
  3. When insulin binds to the cell receptor, it physically changes the cellular membrane, allowing for a countless number of other metabolic actions to occur. It has a cascading effect on cellular and metabolic function.
  4. A few important cell functions that insulin assists with are carbohydrate and fat metabolism and protein synthesis. It regulates cellular energy supply, macronutrient balance, and countless other metabolic processes. It’s a finely tuned system that keeps the body in homeostasis.
  5. Glucose gets used by cells partially based on how much insulin is circulating in the body, which tissues are in need of glucose (energy) at the time, and also by how sensitive the cell receptors are to the presence of insulin.
  6. Insulin is one of many endocrine hormones that work simultaneously and synergistically in the healthy horse. Here are some of the other hormones that need consideration when exploring the causes of insulin resistance:

Cortisol – cortisol (adrenal glands) is also well-known as “the stress hormone” and stimulates the production of glucose in the liver. Chronic stress will raise cortisol and glucose levels and also can cause cells to become “complacent” to circulating insulin by down-regulating cellular insulin receptors (reducing insulin sensitivity).

Insulin-Like Growth Hormone (IGF) – very similar in chemical make-up to insulin. It is involved in regulating growth hormone output, promoting healthy bone and tissue growth.

ACTH (adrenocorticotropic hormone) – made by the pituitary gland and triggers cortisol production under stressful circumstances and also triggers sex hormones in stallions and mares. It is stimulated by daylight hours, IR is a secondary complication related to the development of Cushing’s disease in horses which increases ACTH, cortisol and glucose production by the liver. This causes increased insulin output. Chronic high blood glucose causes a reduction or failure in the sensitivity of the insulin receptor.

There are many other hormones that share a relationship with insulin but these are some of the heavy hitters. While this all sounds complicated, these processes run seamlessly in the healthy horse. It can be difficult to pinpoint the origin of which hormone/gland(s) were affected first. This is why so many factors about the cause of insulin resistance remain a mystery.

When Things Go Awry

The development of equine insulin resistance is the result of the cells losing their ability to allow insulin to bind to the receptor. It is not, as in humans, the inability to produce insulin (diabetes). Without this ability, the cell becomes unable to perform normal metabolic functions. Researchers have studied the exact mechanics of IR development and still don’t completely understand it. This might be because there are so many co-factors to how the disease develops and which hormones are chronically dysregulated. This is why it doesn’t always present with the exact same symptoms in every horse. It is not as straightforward as one would hope. Assessing the individual horse is imperative to finding solutions.

Here are some of the things that we know so far from the research available about the development and conventional management of IR:

  1. Contributing factors to the development of IR are obesity, high-starch diets, lack of exercise, and chronic stress. A combination of these things is the perfect storm. (1)
  2. Minis, ponies, donkeys, Arabians, and Morgans are at particularly high risk for developing EMS. These breeds are bred for extreme climates and utilize glucose more efficiently and, therefore, can easily become obese. Small breeds can also be easily overfed and obese.
  3. IR horses produce excessive amounts of insulin as a result of the complex hormonal dysregulation occurs with high blood glucose levels and/or dysregulated hormone function. In humans, the pancreas can stop producing insulin. This is not common in horses – high insulin secretion can go on for many years before it is properly addressed unless proactive blood testing is done. Many people will notice a “cresty neck” and other abnormal fat storage in specific areas of the body long before their horse is diagnosed. In horses, the disease is a metabolic complication of the cell receptor, not production of insulin. They have lots of insulin in the blood stream with nowhere to go.
  4. The thyroid hormone levothyroxine is often given to horses as a weight loss measure in severely obese horses. It does reduce weight but is variable in its ability to increase insulin sensitivity for all horses. (2) It is advised to check your horse’s thyroid and insulin levels via bloodwork if they are on this medication for extended periods of time as it needs to be adjusted depending on the need of individual horses. It is usually done only based on weight so as the horse loses weight, they may need less and less of the drug. A 2022 study reveals that horses who are over-prescribed levothyroxine can develop heart complications associated with hyperthyroidism. (3) Levothyroxine can also deplete calcium and promote bone loss which can be life-threatening in older horses. It’s important to do regular blood testing when using this drug. Other measures must be taken in tandem with using levothyroxine to ensure the best chance of success in management.
  5. Often, a drug called metformin is prescribed to reduce insulin levels but this does not address the underlying issues. It simply controls symptoms. It also induces vitamin B12 deficiency and so B12 should be monitored for in the blood. B12 can also become depleted due to gut disease, another common issue in horses.
  6. The cells and tissues that are affected can vary depending on the root cause of the disease. The clinical symptoms can vary based on which glands and tissues are most adversely affected. In horses, IR has been linked first and foremost to obesity but newer research also shows that inflammation of the body tissues may also play a role. (4) This opens up a whole new can of worms because there are LOTS of factors that cause inflammation.
  7. Laminitis is a result of insulin resistance. In horses, researchers suspect that laminitis may happen when the cell receptors become confused and a different hormone receptor begins taking up the excess insulin. This receptor is called the insulin-like-growth factor (IGF) receptor. In a healthy metabolic system, IGF regulates normal growth of body tissues, including bone, hair and hoof. Researchers think that when laminitis occurs, it could be a result of accidental IGF hormone uptake, simulating the abnormal growth of the lamellar cells. (5)
  8. Cushing’s Disease (or Pituitary Pars Intermedia Dysfunction/PPID) is an auto-immune disease of the pituitary gland. PPID causes increased secretion of the adrenocorticotropic hormone (ACTH), the hormone that stimulates the production of cortisol. Increased cortisol levels result in chronic increased blood glucose levels and results in IR as a secondary complication. Alternatively, IR can pre-dispose horses to Cushing’s disease so it gets a little more complicated. It’s important to differentiate the IR horse from the Cushing’s horse in order to find the best solutions.
  9. PPID is considered an autoimmune disease of the pituitary BUT with cortisol and ACTH, the interaction can be a chicken or egg scenario. High ACTH will be diagnosed as Cushing’s disease, however, true Cushing’s might be less common than we think. ACTH levels can be chronically high for any or all of the following reasons: chronic stress, insulin dysregulation, head injury (pituitary trauma), chronic systemic inflammation, disturbed circadian rhythm (light/dark/sleep cycles), prolonged high dietary protein or high dietary starch, medications, and gut disease. If one or more of these issues is happening for your horse, it’s time to get to work solving them in a systematic way rather than blindly accepting a Cushing’s diagnosis. You may be able to make a huge difference for your horse without medication.
  10. Zinc deficiency is known to be a contributing factor to insulin resistance in humans and is a common deficiency in horses too. (6)
  11. Calcium, Magnesium, iodine, selenium, chromium and cobalt deficiency are also known to increase risk of IR in humans. (7) Horses have similar risks for deficiency because our soils are depleted in trace minerals largely due to agricultural farming practices.
  12. Environmental and dietary management of IR, chronic inflammation and dysregulated cortisol should be your primary action. Then, you can proceed with further alterations in the care plan once you have checked all of these factors off the list as managed.

IR Risk Assessment: Is Your Horse SAD?

SAD stands for STRESS, ACTIVITY, and DIET. Here’s my SAD assessment system for understanding your horse and where they might need help. This is a great way to prevent the development of IR or formulate a holistic approach with your veterinarian and other equine healthcare professionals if your horse receives this diagnosis.

STRESS

Has your horse experienced prolonged physical stress eg. pain, illness or inflammatory issues?

Inflammation appears to play a significant role in IR developmentYou’ll need to assess your horse’s overall inflammatory load eg. diet and environment. Even chronic sub-clinical systemic inflammation can contribute to insulin resistance (8). Gut inflammation also puts your horse at risk for insulin resistance – disturbing the microbiota that produce enzymes to increase insulin sensitivity. (9) Be proactive and ensure you are not using management methods that might be contributing to gut inflammation in your horses. (Eg. confined quarters, lack of movement, sporadic feeding schedule, processed/high starch feeds, poor hay quality, no turnout, etc.). We’ll discuss gut-friendly foods and lifestyle for horses in a later article.

Is your horse on drugs that might be affecting his insulin sensitivity? 

Antihypertensive agents such as diuretics and β-blockers and corticosteroids have been reported to impair glucose tolerance. (10) If your horse is on these medications, or has been given many rounds of them in the past, you can take a proactive approach to support them with herbs and homeopathics. Do this with the help of an integrative professional and your veterinarian since some herbs are contraindicated with certain drugs.

Does your horse seem emotionally stressed?

Mental/emotional stress may play a significant role in the development of IR, causing glucocorticoid hormone secretion. Chronic increased cortisol will lead to insulin resistance. (11) Horses can display obvious signs of emotional stress but some are stoic about it so make sure you are really honest with yourself about how comfortable they are in their own skin and in their environment. Increased cortisol levels due to chronic stress can also contribute to obesity, increasing the risk of IR. (12)

Is your horse sleeping properly?

Lack of sleep can also change the hormonal regulation of and sensitivity to insulin. (13) This can be related to stress, exercise program, pain, and even the type and amount of bedding you use. It’s a vicious cycle because lack of sleep can cause inflammation and neurological stress, increasing cortisol, epinephrine and other hormones that contribute to IR.

Is your horse over-vaccinated?

Over-vaccination can lead to chronic systemic inflammation and even auto-immune disease. (14) (15) (16) (17) 

ACTIVITY

Does your horse get enough healthy exercise? 

Exercise enhances insulin sensitivity. (18) Be sure your horse is getting enough! Obesity leads to IR. (19) Your horse needs an appropriate exercise program along with an environment that allows for them to walk to maintain a healthy weight and muscle conditioning (which increases insulin sensitivity). Obesity also contributes to inflammatory diseases of joint and cardiovascular tissues which may cause stress and affect insulin sensitivity. The amount of turnout your horse gets can also affect their predisposition to obesity. This balance becomes much trickier once the development of IR has already begun and prevention is ideal. Work with the horse that you have and asses their individual needs.

DIET

Does your horse have a high starch diet? 

Excessive dietary starch contributes to IR. (20) Turf the processed feed. Seriously, do it now… Genetically modified, processed feeds will raise your horse’s blood sugar levels. Concentrated feed becomes starchy when it is excessively heat-treated. Processed (hydrolysable) starch is not an appropriate energy source for any long-term equine diet plan, despite conventional guidelines.

Are you feeding your horse foods that contain the herbicide Roundup?

Roundup (glyphosate), is a chemical herbicide that is science proves is carcinogenic and hormone disruptive. (21) It is also classified as an antibiotic (US Patent # 7771736), causing digestive changes to the microbiome (dysbiosis). Additionally, it is registered as a chelating agent (U.S. patent # 3160632 A), dramatically reducing the bioavailability of trace minerals including manganese, copper, iron, and zinc. These minerals are all indicated for supplementation in the EMS horse. Make sure you’re not feeding processed feed that includes wheat, corn, soy, and canola as they have the highest levels of glyphosate.

Is your horse getting the right kind of dietary fibre?

Resistant starch (the kind that doesn’t break down into sugar) helps to improve insulin sensitivity. (22)  High fibre diets contribute to helping moderate insulin production through the effects of gastric motility, transit time, gastrointestinal hormone secretion, and colonic fermentation which creates short chain fatty acids (in particular, butyrate). (23) Fibre also feeds the healthy microbes that make up the digestive microbiome. Learn which equine foods have good fibre in my second article on insulin resistance (stay tuned).

Is your horse getting adequate minerals and vitamins?

Micro mineral deficiencies may play a role in IR development, particularly zinc, copper, iron, selenium, and chromium.

Vitamin E reduces oxidative stress (which can increase EMS risk) in horses. (24) Most hay is deficient in vitamin E so it is important to use supplementation if that’s all they are eating.

Vitamin B’s and K’s, largely produced in the gut, help to reduce stress (cortisol) and insulin sensitivity. Vit B9 and B12 deficiency (ultimately a result of gut disease) is known to contribute to insulin resistance (25) (26) (27)

Are you starting to get a better picture of what might be going on? A bird’s eye view starts to emerge when you look at all of this research! Even still, there is no manual on how to help all horses. This must be done individually.

Insulin resistance requires a holistic approach which should include close monitoring of clinical signs, diagnostics, diet, integrative tools and, in some cases, medications may be warranted for quality of life. It is a balancing act that can require creative thinking skills in each case. Stay tuned for my e-book where we will discuss the holistic approaches I use to help horses with IR, PPID and other common equine diseases using diet, supplements and herbs, homeopathics, exercise, and stress management.

E-book Release Date: November 15, 2023 – Follow us on Instagram & Facebook for the announcement: @theanimalsynergist

References

  1. Journal of Veterinary Medicine: ECEIM consensus statement on equine metabolic syndrome, 2019
  2. Equimed: Thyroid hormone and equine metabolic syndrome, 2022
  3. Journal of Veterinary Cardiology: Cardiovascular changes in horses with atrial fibrillation and high thyroid hormone concentration: A case-control study, 2022
  4. Veterinary Immunology and Immunopathology: Novel link between inflammation and impaired glucose transport during equine insulin resistance, 2012
  5. The Horse: Grasping Insulin Resistance in Horses, 2019
  6. Nutrition Research and Practice: Effect of zinc supplementation on insulin resistance and metabolic risk factors in obese Korean women, 2012
  7. Nutrition: Role of minerals and trace elements in diabetes and insulin resistance, 2020
  8. Circulation: Chronic subclinical inflammation as part of insulin resistance syndrome, 2000
  9. Nutrients: The Role of Gut Microbiotia on Insulin Resistance, 2013
  10. International Textbook of Diabetes Mellitus 2nd John Wiley & Sons, New York; 1997 p. 213–54
  11. Phychoneuroendocrinology: Role of Stress in the Pathogenesis of the Metabolic Syndrome, 2005
  12. Endocrinology and Metabolism Clinics of North America: Mechanisms of Glucocorticoid-Induced Insulin Resistance, 2014
  13. Clinical Endocrinology: Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes: potential clinical implications, 1999
  14. Zhurnal Mikrobiologii, Epidemiologii I immunobiologii: Development of autoimmune reactions in horses serving to produce antitetanus serum, 1986
  15. Vaccines for Veterinarians: Adverse consequences of vaccination, 2021
  16. Veterinary Pathology: Immune-mediated muscle diseases of the horse, 2018
  17. Advances in Veterinary Medicine: More bumps on the vaccine road, 1999
  18. Applied Physiology: Invited review: Exercise training-induced changes in insulin signaling in skeletal muscle, 2002
  19. Obesity Research: Adiposity and Fat Distribution Outcome Measures: Assessment and Clinical Implications, 2012
  20. Journal of Animal Science: Insulin resistance in the horse: Definition, detection, and dietetics, 2005
  21. Toxicology: Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines, 2009
  22. Nutrition: Resistant starch improves insulin resistance and reduces adipose tissue weight and CD11c expression in rat OLETF adipose tissue, 2014
  23. Nutrients: Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance, 2017
  24. Journal of Internal Veterinary Medicine: A Comparative Review of Vitamin E and Associated Equine Disorders, 2012
  25. Journal of Veterinary Internal Medicine: Insulin dysregulation in horses with systemic inflammatory response syndrome, 2018
  26. Haydarpasa Numune Medical Journal (University of Health Sciences, Turkey): Relationship between insulin resistance and vitamin B12 deficiency in obese children, 2018
  27. Cureus: Role of vitamin B12 and folate in metabolic syndrome, 2021