Equine metabolic syndrome

What it is

Equine metabolic syndrome (EMS) is not a single disease but a cluster of risk factors for endocrinopathic laminitis. The most important is insulin dysregulation (ID), which can appear as:

• Basal hyperinsulinaemia: high resting insulin.
• Exaggerated insulin response to dietary sugars: after a meal rich in sugars or starch, insulin rises much more than normal. The enteroinsular axis plays a part: sugars in the small intestine release incretins that stimulate the pancreas to secrete more insulin.
• Tissue insulin resistance.

It is often accompanied by obesity, general or regional (crest of the neck, tailhead, above the eyes, fat pads), low adiponectin and high leptin and triglyceride concentrations, although some horses with ID are not obese.

Sustained hyperinsulinaemia triggers laminitis; the mechanism is not clear, but insulin is thought to act on growth factor receptors in the hoof lamellae and disturb their epithelium. Horses with PPID can also have insulin dysregulation, and the risk of laminitis depends mainly on the latter.

Who it affects

Mainly ponies and "thrifty" breeds that make very efficient use of feed: British native ponies (Shetland, Welsh), miniature horses, donkeys and horses such as the Andalusian, which has lower insulin sensitivity than other breeds; genetic studies have been carried out in Arabians, Welsh ponies and Morgans. It can occur in any breed. Risk increases with obesity, lack of exercise and access to sugar-rich pasture, especially in spring and autumn. It usually shows in middle-aged adults, younger than horses with PPID.

Anatomy involved

• Hooves: laminitis is the main clinical consequence. The epidermal lamellae of the hoof wall interdigitate with the dermal lamellae covering the third phalanx and keep it suspended inside the hoof. When the lamellar epithelium stretches and weakens, the distal phalanx can rotate or sink inside the hoof. In endocrinopathic laminitis lesions develop more slowly and insidiously than in laminitis from sepsis or grain overload, and divergent growth rings, wider apart at the heels than at the toe, are often seen.
• Pancreas: the β cells of the islets secrete insulin. In equine ID secretion is excessive and diabetes is rare: blood glucose is almost always normal.
• Small intestine: where starch is digested and sugars are absorbed, and where the incretins that amplify insulin secretion are released. This is why tests with oral sugars detect ID better than intravenous ones.

Clinical signs

• General or regional obesity, especially a thick, firm cresty neck.
• Acute or chronic laminitis, sometimes mild and recurrent: stiffness, weight on the heels, reluctance to turn, increased digital pulse, divergent rings in the hoof wall.
• Many horses show no signs until their first episode of laminitis.

Diagnosis

• History and examination: body condition, neck crest, previous or current laminitis.
• Non-fasted basal insulin (with the horse eating hay): a high value confirms ID, but a normal value does not rule it out.
• Dynamic tests with oral sugars: the oral sugar test (corn syrup) or the in-feed glucose test; insulin is measured 60–90 minutes later. These are the most recommended.
• In older horses PPID should be ruled out by measuring ACTH, because both can coexist.

Treatment and prevention

• Diet: the foundation. Cereals and sugary feeds are removed, and low-sugar hay is fed (analysed or, if not, soaked to reduce sugars), weighed and, if the horse needs to lose weight, restricted to 1.25–1.5% of body weight as dry matter per day according to the consensus, with a vitamin and mineral supplement. Access to pasture is limited or removed, or a grazing muzzle is used. Extreme restriction must be avoided, especially in ponies and donkeys, because of the risk of hyperlipaemia.
• Regular exercise if the horse has no active laminitis: it improves insulin sensitivity as well as helping weight loss.
• Drugs as an aid when diet and exercise are not enough: levothyroxine to speed weight loss, metformin (with poor oral absorption in the horse and doubtful efficacy) and SGLT2 inhibitors (velagliflozin, canagliflozin, ertugliflozin), which lower insulin by increasing urinary glucose loss; their use in horses is still off-label in most countries and they can raise triglycerides.
• Laminitis: analgesia, frog and sole support, rest on deep soft bedding and insulin control.
• The horse is a food-producing species in many countries. In the EU its passport states whether it is excluded from the food chain, and this determines which medicines may be used and with which withdrawal periods.

Key studies

• ECEIM consensus (Durham et al., 2019): defines EMS as a cluster of risk factors for endocrinopathic laminitis, with insulin dysregulation as the most important. Diagnosis combines history, examination and laboratory tests, and control relies on diet and exercise, with drugs as an aid in some cases. It is expert opinion; several authors declared links with drug manufacturers and diagnostic laboratories.
• Menzies-Gow et al. (2017), prospective cohort of 446 non-laminitic ponies aged 7 years or more, followed for 3 years. 72.2% were overweight or obese. Laminitis developed in 4.0% at one year, 6.7% at 2 years and 9.9% at 3 years. Low adiponectin and high basal or post-dexamethasone insulin predicted laminitis. Measurements were taken once, at the start, and laminitis episodes were reported by owners.
• Knowles et al. (2023), prospective cohort of 374 non-laminitic ponies followed for up to 4 years (891 pony-years). Incidence was 4.8 cases per 100 pony-years. By basal insulin, the 4-year risk was 6% in the low category (< 21.6 µIU/mL), 22% in the medium and 69% in the high (> 45.2 µIU/mL); by insulin 60 minutes after the oral sugar test, 3%, 20% and 73%. ACTH was not independently associated with laminitis. Cut-offs depend on the insulin assay used and on the population.
• Meier et al. (2018), study in 49 ponies with ID randomly assigned to velagliflozin (12) or control (37) and fed an experimental diet very rich in non-structural carbohydrates. Velagliflozin lowered peak insulin by 45%, and none of the treated ponies developed laminitis versus 14 of 37 controls (38%). The treated group was small, laminitis was induced with an extreme diet and the study was funded by the manufacturer.
• Bamford et al. (2019), study in 24 obese horses and ponies over 12 weeks: dietary restriction alone versus restriction plus low-intensity exercise on a walker. Weight loss was similar in both groups, but only exercise improved insulin sensitivity and reduced an inflammatory marker (serum amyloid A). It is a small, short study.