Equine Metabolic Syndrome

Also known as: EMS, Peripheral Cushing's syndrome, Pre-laminitis syndrome, Pre-laminitic metabolic syndrome

Introduction

Equine Metabolic Syndrome (EMS) describes a collection of risk factors that predispose horses to the development of endocrinopathic laminitis. The main feature of the condition is insulin dysregulation, although there are a number of metabolic processes that contribute.

Aetiology

EMS is a hormone disorder which causes insulin resistance. The official definition of EMS is ‘a collection of historical, clinical and laboratory risk factors for endocrinopathic laminitis’ however insulin dysregulation is the most important feature of the disease. The pathophysiology is extremely complex and is not yet fully understood. Like many endocrine conditions, EMS has an insidious onset.

Increasingly the endocrine function of adipose tissue is being recognised, and this is thought to play a major role in pathgenesis of EMS. EMS is most common in overweight animals, although not all animals are obese.

The exact pathogenesis of endocrinopathic laminitis in horses with EMS is unclear, but high resting blood glucose concentrations, inflammatory mediator release from fat, alterations in steroid hormone metabolism by adipose tissue and direct functions of insulin are all thought to play a role.

Epidemiology

There are a number of intrinsic and environmental factors which are involved in the development of EMS:

• Genetic predisposition: EMS is more common in ponies, particularly native breeds
• Age: older horses are less sensitive to insulin
• Obesity: excess intake of calories with respect to exercise/ metabolic requirements (over a prolonged period)
• Epigenetic factors: excessive or undernutrition in utero can alter metabolism later in life
• Dietary factors: high CHO diets
• Influence of the GI microbiome

The most common presentation of EMS is recurrent laminitis in 5-15yo ponies with a high BCS.

Pathogenesis

Adipocytes have an important (but often overlooked) endocrine function within the body. They produce hormones (adipokines) which act systemically in a number of processes.

Animals with EMS have increased concentrations of adipokines which antagonise the effect of insulin and cause hyperglycaemia. The body responds to this by increasing insulin production and the ultimate effect of this is hyperinsulinaemia. If this continues for a prolonged period of time, some animals may develop beta cell exhaustion, where the pancreas can no longer produce insulin (i.e. Type 2 diabetes).

It is unclear what role this hyperinsulinaemia plays in the pathogenesis of laminitis, but it has been suggested that stimulation of IGF-1 receptors may cause endothelial dysfunction.

Insulin resistance results in high blood glucose concentrations, which can damage blood vessels and alter blood flow to the hoof- contributing to laminitis.

Fat plays an additional role in steroid hormone metabolism, which also antagonise insulin. Steroid-like hormones can be primarily produced by fat cells, but adipocytes also have the ability to convert inactive cortisone into the active molecule cortisol.

Many cases of EMS go undiagnosed, despite high levels of obesity, laminitis and hyperinsulinaemia in the equine population. There are a number of owner and veterinarian directed campaigns highlighting the effects of equine obesity and EMS.

https://www.beva.org.uk/Home/Guidance-and-Resources/Routine-Healthcare/Equine-Obesity

https://www.liverpool.ac.uk/equine/common-conditions/weight/

https://www.worldhorsewelfare.org/advice/management/right-weight

Clinical Signs

• Obesity: BCS >3/5; abnormal fat accumulation along the crest, shoulders, tailhead and rump • Laminitis (chronic): dropped sole, divergent growth lines on hoof wall, widened white line • Laminitis (acute): FL lameness (shifting weight, pottery gait, reluctance to move), pain (increased HR, RR, behavioural changes), increased digital pulses, heat around foot

Diagnosis

Diagnosis should be suspected based on clinical signs and patient history. Blood testing can help confirm a diagnosis (and is often used to rule out PPID which is the main differential diagnosis).

Resting insulin levels (interpreted alongside glucose) can give a good indication of insulin resistance. Glucose levels are rarely above the reference range but tend to lie towards the upper end. High glucose levels are often a sign of severe insulin resistance. Glucose values can also be affected by stress, so care when interpreting high values. In some cases insulin levels may be low, where beta cell exhaustion has occurred.

Dynamic tests are more accurate for diagnosis, and there a number of different techniques available:

Oral Glucose Tolerance Test (OGTT) : 1g/kg glucose is administered as a 20% solution and blood glucose and insulin levels are tested prior to administration and at 30, 60, 90, 120, 150, 180, 240 min. Blood glucose should double within 2 h and normalise within 6 h. Glucose (>11.1mmol/l) or delay to normal levels indicates insulin resistance. Using the insulin levels as well as glucose gives more information and the I:G ratio can be a useful measure. >0.3-0.5 indicates relative insulin resistance. Total insulin secretion is also raised with insulin resistance. Horses with type 2 DM (rare) may have low/normal insulin and high resting glucose or glucose responses (as the beta cells are no longer producing adequate amounts of insulin). Beware of other conditions which could affect this test e.g. gastrointestinal function.

Intravenous Glucose Tolerance Test (IVGTT) 0.5g/kg dextrose is given IV as a 50% solution following 12 h fast. Samples for glucose and insulin are collected at 0, 0.25, 0.5, 1,2,(3,4,5,6) h. Normal is >300% increase in glucose @ 15 min followed by rapid decrease alongside more than 600- 700% increase in insulin @ 15 and 30 min, followed by a decrease. Glucose and insulin concentrations should return to baseline within 1 h.

Insulin Tolerance Test (ITT) 0.05IU/kg insulin is given IV. Blood samples for glucose and insulin are taken at 0, 30, 60, 90, 120, 180, 240, 300 min. Normal response is 30-50% decrease in insulin at 15 min, 60% at 30 min. Normal levels should be reached by 2 h. CARE not to induce hypoglycaemia with this test.

Combined Intravenous Glucose and Insulin Tolerance Test (CGIT) Collect baseline blood sample for glucose and insulin. Infuse 50% dextrose (0.15 g/kg), immediately followed by 0.10 units/kg regular insulin. Further samples are collected for glucose at 1,5,25,35,45,60,75,90,105,120,135, and 150 min; and for insulin at 45 min. Impaired glucose tolerance is shown by the maintenance of blood glucose above baseline for >45 min. Insulin levels should decline to < 100 IU/ml by 45 min; anything longer is suggestive of IR.

For all of these tests horses may have small amounts of forage and water without affecting test results, but concentrates should be withheld for at least 12 hours.

Differential Diagnosis

The other main cause of endocrinopathic laminitis is PPID (Equine Cushing’s disease). Resting ACTH levels may help exclude this disease, but raised levels combined with clinical suspicion may indicate that dynamic tests are required (e.g. TRH response test).

Treatment

The key to controlling EMS is dietary control and exercise. If cases are recognised early, then strictly implemented management strategies to reduce weight and control diet may prevent the development of laminitis. Care should be taken when devising a weight loss plan because severe caloric restriction can lead to hyperlipidaemia. Furthermore, severe calorie restriction promotes metabolic processes designed for survival in poor conditions, where insulin resistance is increased and energy is conserved which prevents weight loss. Overweight horses should not be given access to rich grazing, and ideally owners should have the sugar content of their hay analysed. Hay should be soaked for at least 12 hours to remove some of the soluble carbohydrate. Having horses out at pasture can help promote natural exercise, however grass muzzles may need to be used to prevent overgrazing on rich grass. An alternative solution is to graze these animals at night when the sugar content of grass is lowest. If additional feeding is required then foods with a low glycaemic index should be used. Unmollassed sugar beet or alfalfa chaff are good examples of low GI foods, or there are some commercial feeds designed for laminitics. In some situations it may be helpful to consult a nutritionist (who will often help analyse hay samples with minimal expense). Ideally dietary modification should be combined with increased energy expenditure through exercise, but in some individuals it is difficult to increase exercise due to laminitis and associated pain. In these cases dietary management is the main component of the weight loss plan. Historically thyroid hormone supplementation has been used in overweight ponies under the belief that they are hypothyroid. This is unlikely in most animals, and treatment with thyroxine is not indicated. In some cases it may be used in the short term to aid weight loss but ideally simple management changes should be attempted first.

Prevention

Owner education is key in the prevention of EMS. Animals predisposed to obesity and EMS should be managed carefully to prevent excessive weight gain, and as with many things prevention is better than cure. Often conveying this to owners requires highly skilled communication, as they feel that they are being kind to their horse by feeding them things that they enjoy or rugging them unnecessarily.

There are a number of resources circulated in the veterinary and equestrian press which can be helpful. Some examples are included above.

References

Vetstream Vetlexicon Equis: Equine Metabolic Syndrome https://www.worldhorsewelfare.org/advice/management/right-weight RDSVS staff (2019) PPID, EMS and weight loss in horses' BVM&S Intergrated Clinical Course: Equine, Royal Dick School of Veterinary Studies

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