equine metabolic syndrome

There are significant numbers of donkeys kept as companion animals, both in the UK and abroad. Like their horse and pony compatriots, many kept donkeys are geriatric. Additionally, obesity is a common problem, irrespective of age. Diagnosis and management of endocrine disease in donkeys is challenging as many of the available tests for horses have not been specifically validated in donkeys. Furthermore, endocrinopathic laminitis in the donkey is not infrequently subclinical. The term ‘subclinical,’ is perhaps inappropriate, for the lack of clinical signs may not correlate with the severity of the laminitis episode but instead be a feature of the donkey’s notoriously stoic behaviour with respect to pain.

As a species, the donkey has evolved to be extremely energy efficient, with an inherent ability to maintain good body condition on lower energy diets. They have a slower intestinal transit time and greater efficiency of fibre digestion than the horse [1]. Donkeys appear able to accumulate adipose tissue with ease. Whilst these innate traits serve the working donkey or those kept in harsh environments where food resources are scarce well, they predispose the sedentary donkey to obesity, dyslipidaemias, insulin dysregulation and other metabolic disorders.

Donkey, or asinine, metabolic syndrome is increasingly recognised by equine veterinary practitioners. Clear and precise definitions are lacking and currently rely on extrapolations from equine metabolic syndrome. The clinician presented with an obese donkey should be suspicious of underlying metabolic derangements. The donkey may be generally obese, or have defined regional adiposity, with deposits along the neck, dorsum and rump being common. There are usually substantial subcutaneous fat deposits on the ventral abdomen in obese donkeys. Awareness of the obese donkey may only arise when the otherwise healthy donkey is presented for routine preventative care, such as vaccination or dental care. This provides an ideal opportunity to discuss the donkey’s body condition and diet, with the intention to reduce development of metabolic disease. Initial clinical assessment must include an evaluation of any indicators of laminitis, whether subtle or overt. The donkey that is described as unwilling to walk may actually be in discomfort rather than being unused to handling. It is imperative that provided diets are appropriate for the donkey’s life stage. For the adult, healthy donkey, with good molar function, the majority of forage intake should be provided by straw, with hay/haylage or restricted grazing making up the remainder of the diet. Owners should be advised to aim for straw to provide 75% of intake in summer and 50% in winter. Supplementation with a vitamin and mineral balancer is recommended. The conscientious owner may be willing to have their forage sugar content analysed, to further guide dietary management.

If a donkey remains obese, despite sufficient time and appropriate diet for expected weight loss to ensue, further investigation for metabolic disease should be undertaken. Basal insulin concentrations may be elevated in obese donkeys. The established reference range at The Donkey Sanctuary for a non-fasted insulin sample in the adult donkey is 0-15.1 uIU/ml (TOSOH AIA, using two-site immunoenzymometric serum assay). As for horses, a normal insulin concentration does not rule out insulin dysregulation and dynamic tests are recommended for further investigation. Protocols have been developed for donkeys, with intravenous glucose tolerance test, combined glucose-insulin test and oral glucose tolerance tests described in the literature [2] but insulin cut-off values for these tests have not been validated for donkeys. In the author’s clinic, the oral glucose tolerance test with corn syrup is used as this provides an accessible and practical dynamic test. The major limitation being that the protocol used is that developed for horses and may not be directly transferable to donkeys and, again, there is no validated insulin cut-off value. Consequently, diagnosis of asinine metabolic syndrome is currently made based upon combinations of clinical observations, poor weight loss despite appropriate diet, evidence of hyperinsulinaemia or insulin dysregulation and history of laminitis episodes.

Management of asinine metabolic syndrome is as challenging as the diagnosis. Many owners struggle to appropriately diet their donkey, particularly if any companion is not obese and/or has different dietary requirements. It is now widely understood that donkeys form strong bonds with their companions and can become distressed and at risk of hyperlipaemia if separated. However, for short periods if one donkey needs supplementary feed companions can be kept in sight of each other, yet physically separated by a fence or stable door. Owners should also try to encourage their donkeys to exercise, which is admittedly no mean feat. Turn out onto a bare pasture, which donkeys can explore and exercise within, is likely to carry more benefit than stabling a donkey away from rich grass pastures. If a donkey is accepting of a head collar and being led, many owners enjoy taking their animals for short walks. Providing enrichment activities that encourage the donkey to be mobile and explore are also helpful.

It goes without saying that exercise should not be advised until active laminitis has been ruled out. An association between obesity, insulin dysregulation and recurrent laminitis in donkeys has been reported but in a recent cross-sectional study of 707 donkeys in the UK [3], the presence of basal hyperinsulinaemia or PPID (indicated by seasonally adjusted elevations in ACTH) was not associated with increased odds of laminitis. However, this study acknowledged the lack of validated dynamic testing for either PPID or AMS and the potential errors in classification of cases. In the absence of definitive knowledge, clinicians should err on the side of caution and be alert to the potential for endocrinopathic laminitis. Management of laminitis in the donkey has been covered elsewhere [4].

The use of medication to treat asinine metabolic syndrome has not been extensively evaluated. As for horses, therapeutic protocols should only be used as an adjunct to dietary and exercise management. The use of levothyroxine in the donkey at standard equine doses has been reported [2]. Studies are needed to assess the safety and efficacy of ertugliflozin in the donkey, alongside any other medication proposed for treatment of metabolic syndrome in the horse.

References:

[1] Thiemann AK, Sullivan RJE. (2019). Gastrointestinal Disorders of Donkeys and Mules. Vet Clin North Am Equine Pract 35(3):419-432

[2] Mendoza FJ, Toribio RE, Perez-Ecija A. (2019) Metabolic and Endocrine Disorders in Donkeys. Vet Clin North Am Equine Pract 35(3):399-417

[3] Menzies-Gow NJ, Wakeel F, Little H, Buil J, Rickards K. (2021). Cross-sectional study to identify the prevalence of and factors associated with laminitis in UK donkeys. Equine Vet J. 54(4):757-765

[4] Thiemann A.K, Buil J, Rickards K, Sullivan R.J (2021). A review of laminitis in the donkey. Equine Vet Educ 34(10): 553-560

Laminitis is a relatively common, painful condition of donkeys, ponies and horses. The underlying principles of pathology, diagnosis and treatment are broadly similar, but there are features of donkey anatomy, behaviour and physiology that differ from the horse; understanding these will improve treatment outcomes (Thiemann et al, 2021).

A study of over 2500 donkeys in the UK, found a prevalence of 4% of donkeys presented with laminitis with 46% of cases acute and 54% chronic. This is likely to be an underestimate due to the high levels of obesity and poor detection of the disease.

Recognition of laminitis

Few donkeys in Europe work, most are companion equines. This often results in late detection of laminitis in this species. Typically, signs are subtle, and include altered posture, stiff or shuffling gait and lameness on turning. There may be increased digital pulses and pain to hoof testers. Many donkeys will just lie down, and some owners can misinterpret this as normal resting behaviour.

In chronic cases, there will be abnormal growth rings on the hoof, a flatter sole and, in severe cases upper limb muscle atrophy and flexor tendon breakdown.

Using the Donkey Facial and Donkey Composite pain score (Van Dierendock, et al 2020) enables clinicians to quantify donkey pain and monitor response to treatment and analgesia.

The anatomy of the donkey hoof varies from the horse- P3 sits further distal and there is typically 10mm “founder distance” as normal between the coronary band, and top of the extensor process. The frog tissue is further back on the distal border of P3, this makes use of a heart bar shoe inadvisable. A normal hoof should have at least 10mm sole depth. The external hoof wall is approximately 5° more upright than a horse, but the phalanges, pastern and dorsal hoof wall should align.

Radiographs of donkey hooves need interpreting using donkey parameters.

Obese donkeys suffer from Asinine Metabolic Syndrome (AMS) and donkeys with Body Condition Score >3 (scale 1-5) are at risk. Donkey specific BCS charts and weight nomograms are available (The Donkey Sanctuary, 2020a & 2020b) to assist with assessment. Basal insulin and karo lite testing can be used to confirm a diagnosis of AMS.

Elderly donkeys can develop PPID and, as in the horse, seasonally adjusted donkey specific reference ranges are available.

Treatment of laminitis

As in the horse, the basis of treatment consists of rest, analgesia, foot care and dietary adjustments. In the donkey acute pain and stress, or rapid change in diet may precipitate life- threatening hyperlipaemia (Burden et al, 2011). Ensure the donkey’s appetite and demeanour are closely monitored, and while it is appropriate to reduce the sugar content of any fibre being fed, a reduction in fibre or attempts to diet an obese donkey should be done in a gradual manner.

Donkeys metabolise all NSAIDs (except carprofen) faster than horses, and after a loading dose of 4.4mg/kg BID of phenylbutazone, long term use at 2.2mg/kg BID is considered safe with less risk of dorsal colon ulceration. Meloxicam has a short half- life in donkeys (6 hours) and there is little data on newer NSAIDS. Paracetamol is a useful adjunct at 20-25mg/kg BID. Miniature donkeys require TID dosing for adequate analgesia.

Digital hypothermia is well -tolerated by donkeys and can be useful in acute cases or as preventative in sepsis cases.

In acute cases foot support is best provided with a deep bed, and whole hoof padding or using a commercially available sole support.

Corrective farriery after an episode is an important part of rehabilitation of the hoof, and for chronic cases with flat soles the use of acrylic rim shoes may assist in providing comfort.

Medical support for underlying AMS or PPID is similar to in the horse. The Donkey Sanctuary has little experience yet with the use of levothyroxine to aid weight loss, or insulin lowering drugs such as ertuglifloxin. Pergolide for the reduction of ACTH is known to cause appetite suppression in some donkeys, so when used, the donkey needs careful monitoring.

Prevention of laminitis

Preventative medicine in donkeys is often poor (Barrio et al, 2020), and engaging with owners about correct nutrition, weight management and farrier care is a good strategy. The Donkey sanctuary provides an online resource “The Donkey Academy” with free courses for owners, vets and farriers to assist in this area, as well as fact sheets and handbooks: https://www.thedonkeysanctuary.org.uk/research/what-we-do/knowledge-and-advice/donkey-academy

Donkeys with good dentition cope well on a high fibre, low starch diet where straw provides the bulk of the forage, supplemented by a small amount of vitamin/mineral balancer (Burden et al, 2019). If dieting is needed, suitable mental stimulation helps with prevention of stereotypic behaviour developing (The Donkey Sanctuary, 2020c).

In many cases severe chronic laminitis is undetected and vets and owners can work together to understand the impact of this on Quality of life and End of life Decision-making. The stoic nature of donkeys can results in prolonged unacceptable suffering.

References

1) Thiemann, A. K., Buil, J.and Rickards, K.(2021). A review of laminitis in the donkey. Equine Veterinary Education. 34(10) 553-560. Available from: doi.org/10.1111/eve.13533

2) Van Dierendonck M.C., Burden, F.A. and Rickards, K. (2020). Monitoring acute pain in donkeys with the Equine Utrecht University Scale for Donkeys Composite Pain (EQUUS-DONKEY-COMPASS) and the Equine Utrecht University Scale for Donkey Facial Assessment of Pain (EQUUS-DONKEY-FAP) Animals.10(2) 354. Available from: doi.org/10.3390/ani10020354

3) The Donkey Sanctuary (2020a) Donkey Body Condition Score chart. Available from: https://www.thedonkeysanctuary.org.uk/research/sites/uk/files/2020-01/body-scoring-chart-revised-01-2020.pdf.

4) The Donkey Sanctuary (2020b) Donkey weight nomogram. Available from: https://www.thedonkeysanctuary.org.uk/research/sites/uk/files/2020-01/donkey-weight-estimator-chart-revised-january-2020.pdf

5) Burden, F. A., Du Toit, N., and Hazell-Smith, E. (2011). Hyperlipaemia in a population of aged donkeys: description, prevalence, and potential risk factors. Journal of Veterinary Internal Medicine. 25(6)1420-5.

6) Barrio, E., De Blas Giral, I., Thiemann, A. K. and Vasquez Bringas, F. J. (2020) Demography, preventative health care and reasons for relinquishment of donkeys to an equine charity. Equine Veterinary Journal. 53(2) 324-330. Available from: doi.org/10.1111/evj.13310

7) Burden, F. A. and Bell, N. (2019) Nutrition and Malnutrition of donkeys. Veterinary Clinics of North America Equine Practice 35(3) 469-479.

8) The Donkey Sanctuary (2020c). Environment Enrichment: The Donkey Sanctuary’s Guide to Enriching the Lives of Donkeys and Mules. Available at: https://view.pagetiger.com/EnvironmentalEnrichmentforDonkeys/EnvironmentEnrichmentfordonkeys [Accessed September 19 2020].

Equine Metabolic Syndrome is defined as a “Clinical syndrome associated with an increased risk of laminitis that includes insulin dysregulation and any combination of increased generalised or regional adiposity, weight loss resistance, and altered adipokine concentrations.” https://sites.tufts.edu/edu/equineendogroup. Donkeys are prone to Equine Metabolic Syndrome due to their physiological adaptations to survive in resource poor environments. The donkey has a lower nutritional requirement than a pony of the same size, but is often exposed to excess feed with high non- structural carbohydrate levels. In addition, they are generally given little exercise.

Donkeys and many small pony breeds are considered to be relatively insulin resistant- which has a survival advantage, but also leads to, and is linked with both hyperinsulinemia and obesity.

As well as clinical symptoms we need to test for insulin dysregulation. Resting insulin levels have very low sensitivity /high specificity and should not be relied upon as a sole test. At The Donkey Sanctuary we use an oral carbohydrate challenge using Karol Light (corn syrup). As donkeys are at increased risk of hyperlipaemia we do not starve patients before testing, but have a standard protocol that involves the donkey only having access to straw for at least 6 hours prior to testing. We then give 45ml/100kg of syrup and obtain baseline blood samples. A second sample is taken 60-90 minutes later to measure serum insulin, which should be below 60mU/L.

At present adipokine testing is not validated for donkeys.

There will be cases of EMS that do not demonstrate obesity and cases that also suffer from concurrent PPID, so in some cases further diagnostics will be warranted. In many cases management of EMS relies on improving the dietary management of the donkey, and initiating a controlled weight loss programme. Ideally, the exercise is increased, but this will be dictated by whether there is any underlying lameness. To prevent boredom in cases of dietary restriction there are several ways to modify and enrich the stable environment.

Medical treatments exist: metformin can be used to reduce glucose absorption enterically and help in transitioning a donkey to pasture; a thyroxine derivative may be useful to increase the metabolic rate.

Pituitary Pars Intermedia Dysfunction (PPID) is seen in donkeys and, as many are kept until they are geriatric it is seen relatively frequently. The condition is known to be associated with an increased risk of immunosuppression and laminitis. Affected cases may have obvious clinical signs such as hirsutism, muscle wastage and polydipsia. However we rely upon testing suspect donkeys for elevations in ACTH to detect cases before such signs are reached.

PPID results in hyperinsulinemia, which is a risk factor for laminitis. We also find these cases may have higher faecal egg counts, higher ectoparasites burdens and delayed wound healing.

Treatment of the underlying disorder relied upon the use of pergolide- Prascend at 2µg/kg. As the drug can suppress appetite donkeys need careful monitoring when on the drug and may need to start at lower doses. Testing In autumn when the levels are at their highest is considered the best time to discriminate for positive cases.