Insulin Resistance: A Complete Guide

Insulin resistance is associated with a range of diseases in both horses and humans. In horses, it is linked to conditions such as laminitis, hyperlipaemia, Equine Metabolic Syndrome (EMS), Cushing's disease (PPID - Pituitary Pars Intermedia Dysfunction), osteochondrosis, colic, and grass founder. In humans, insulin resistance is connected to type II diabetes, obesity, cardiovascular disease, hypertension, polycystic ovary syndrome, and colorectal cancer.

What Does ‘Insulin Resistance’ in Horses Mean?

To understand insulin resistance in horses, we need to delve into a bit of biology. Insulin, produced by the pancreas, regulates blood glucose levels. It binds to muscle, liver, and fat cells, allowing glucose to enter these cells for energy use and storage. As glucose moves into these cells, blood glucose levels drop back to normal, and insulin levels also return to their resting state.

In insulin-resistant (IR) horses, muscle, liver, and fat cells do not respond to insulin. Consequently, glucose cannot enter the cells, and blood glucose levels remain high. This prompts the pancreas to release more insulin (sometimes up to 100 times more) in an attempt to lower blood glucose levels. Over time, the pancreas becomes exhausted and can no longer produce insulin. Additionally, cells that do not respond to insulin cannot take up glucose and become starved of energy. Muscles, which use around 80% of the glucose in the blood, may show increased tension, unwillingness to work, lethargy, and muscle wastage if they cannot obtain enough glucose.

High blood glucose levels lead to increased body fat, causing inflammation. This inflammation produces harmful chemicals that can exacerbate IR. Furthermore, the combination of high blood glucose and high insulin levels damages blood vessels throughout the body, disrupting cellular processes and resulting in tissue and organ damage, leading to various diseases. The role of insulin in the expansion and contraction of blood vessels is thought to underlie the link between IR and laminitis. The hoof blood vessels are extremely sensitive to blood supply, and when damaged, the bond between the hoof and the coffin bone weakens and degenerates, causing the hoof to separate from the coffin bone.

Why Does Insulin Resistance Occur?

Among both horses and humans, there are individuals commonly known as "easy keepers" or "good-doers." These individuals have lower nutritional requirements, meaning they are metabolically efficient and possess what is known as a "thrifty genotype." This genetic makeup was a critical survival mechanism, increasing appetite and haircoat thickness in autumn to ensure fat stores were built up before winter.

The degree of insulin resistance (IR) varies between different types of cells. Muscles become insulin-resistant before liver and fat cells, ensuring that blood glucose is preferentially diverted to fat for winter storage. At the end of winter, body fat stores are depleted, and IR reverses. Horses with a thrifty genotype, adapted to food-poor winters and relying on grass, are prone to obesity and IR when food is available year-round, especially if the feed is energy-rich and the horse is physically inactive.

The extent to which different horse breeds have inherited thrifty genes is not fully known, but ponies, Morgans, domesticated Spanish mustangs, European Warmbloods, and American Saddlebreds are more prone to both IR and laminitis. Temporary IR can occur due to infections, injury, starvation, pregnancy, and puberty. During pregnancy, IR ensures glucose is redirected to nourish the growing foal rather than being taken up by the mare's body. In young horses, IR has been associated with osteochondrosis due to damage to blood vessels in joint cartilage.

The risk factors, short and long-term consequences, and symptoms of IR are highly diverse and vary between individual horses.

Insulin Resistance and Body Fat
Obesity is a growing problem among domesticated companion horses. A recent study found that 19% of these horses are obese (BCS 8 or 9), and 32% are overweight (BCS 6.5–7.5). Obesity is associated with insulin resistance (IR), exacerbates IR, and increases the risk of laminitis. Additionally, obesity causes chronic inflammation, which plays a major role in the development of IR. Fat, now understood to be more than just a repository for stored energy, produces harmful chemicals that cause inflammation throughout the body.

The composition and inflammatory state of fat varies depending on its location in the body. In humans, regional fat accumulation, particularly abdominal fat, has damaging health consequences. It is linked to changes in blood glucose levels and is a risk factor for IR, diabetes, and other diseases. Similarly, increased fat deposits along the neck crest in horses and ponies (nuchal crest adiposity) are associated with altered metabolism. Fat crests are an adaptive mechanism for fat storage during periods of nutritional scarcity and vary between winter and summer, with lower levels at the end of winter. Crest fat takes longer to develop and deplete than other fat stores, and, like abdominal fat in humans, it disrupts glucose and insulin regulation. It is correlated with metabolic changes that accompany IR.

Measuring the girth-to-height ratio is a good indicator of overall fatness. While IR can also occur in normal and lean horses, they often have abnormal fat accumulations and distribution.

Insulin Resistance and Equine Metabolic Syndrome (EMS)
Equine Metabolic Syndrome (EMS), also known as insulin-resistance syndrome, includes a history of laminitis, insulin resistance (IR), and a characteristic physical appearance such as a cresty neck, bulging fat above the eyes, and increased fat over the withers and back. Studies in herds of ponies have shown that EMS has a strong hereditary (genetic) component.

Insulin Resistance and Laminitis
Horses suffering from laminitis and insulin resistance often have a slow recovery process. However, recovery is more likely if insulin sensitivity is improved. Horses with insulin resistance have a higher risk of developing laminitis, so identifying and treating horses with insulin resistance can help prevent laminitis.

Ponies predisposed to pasture-associated laminitis are metabolically different from those not at risk—they are insulin-resistant. The link between pasture-associated laminitis and underlying insulin resistance was discovered in the 1980s when ponies with a history of laminitis were found to be insulin-resistant and have high blood pressure.

Insulin Resistance and Cushing’s (PPID)
The pituitary gland prepares horses for winter by stimulating appetite, promoting the acquisition of a winter coat, and increasing fat synthesis in autumn. Dysfunction of the pituitary gland, known as Pituitary Pars Intermedia Dysfunction (PPID) or Equine Cushing’s Disease (ECD), occurs in 30% of horses over 15 years old, with ponies and Morgan horses being most at risk. Factors contributing to PPID are unknown, but age, oxidative stress, and chronic inflammation are risk factors. Most, but not all, horses with PPID have insulin resistance.

Signs of PPID include changes in fat distribution (pot belly, muscle wasting, and bulging fat above the eyes), increased drinking and urination, and a higher risk of infections and laminitis. PPID may arise as a result of chronic insulin resistance in obese horses and ponies that have been fed energy-dense rations over many years. Many horses with a thrifty genotype and insulin resistance develop PPID later in life.

Diagnosing Insulin Resistance

Diagnosing insulin resistance (IR) in horses can be challenging due to the wide range of signs and symptoms, and a simple, reliable diagnostic method is still not available. Since obesity is associated with IR, assessing body condition score (BCS) is a helpful tool for general obesity, but it does not account for neck and local fat accumulation.

A BCS greater than 6 (on a scale of 1 to 9) indicates a high risk for IR and laminitis. Local fat accumulations, especially in the neck region, are strongly associated with IR. A more specific scoring system based on neck fat has been developed, with scores ranging from 0 to 5. A score of 0 indicates no signs of fat accumulation on the neck, while a score of 5 indicates severe fat accumulation. A score greater than 3 is described as a "cresty neck." Interestingly, changes in the thickness of the neck have been linked to changes in the severity of IR: as the neck thickens, signs of IR (such as laminitis) tend to increase. These signs decrease when treatments improve insulin sensitivity and reduce neck crest thickness. Measuring neck circumference relative to height and girth is a practical index for suspecting IR, similar to using waist circumference as an indicator of high BMI and IR in humans.

Blood tests for insulin are useful for predicting the risk and prognosis of laminitis. Other tests may be needed to diagnose the range of IR-associated diseases, including ACTH and thyroxine levels.

Managing Insulin Resistance

Improving insulin sensitivity (reducing IR) in horses involves several key strategies:

• Exercise: Regular physical activity helps maintain ideal body condition and enhances insulin sensitivity.

• Diet: Avoid high-glycaemic feeds, pastures, and molasses. Feeds rich in carbohydrates combined with insufficient exercise are major contributors to the development of insulin resistance. The reasons domesticated animals develop obesity are broadly similar to why humans become overweight.

• Management: Prevention and treatment of IR in horses must be based on changing their management and feeding practices.

Pharmacologic agents can also be part of the treatment for conditions like laminitis and PPID. These include Chromium, Metformin, Levothyroxine, Corticosteroids, Pergolide, and Xylazine.

The pros and cons of each medication, the most appropriate choice for your horse, and the best treatment schedule should be discussed with your veterinarian.

Dr Jennifer Stewart
BVSc BSc PhD Equine Veterinarian and Consultant Nutritionist