20 Jul 2015
David Rendle
Job Title
Figure 1. Portable weighbridges are an excellent means of monitoring horses with EMS.
Laminitis was once assumed to occur as an end point of a single pathophysiological pathway that may have had a number of triggers. However, it has become more apparent the pathophysiology of laminitis is complex and a number of different processes ultimately result in separation of the lamellar basement membrane1. An epidemiological study this year demonstrated supporting limb laminitis in lame horses is extremely uncommon2 and most laminitis cases in the UK occur in grazing horses. An increasing body of evidence indicates endocrine dysfunction is central to most of these cases3,4 and effective management of endocrine disease is, therefore, central to prevention of laminitis.
A case control study in 2013 identified a number of risk factors
for laminitis, namely5:
Other (less robust) studies have identified additional risk factors:
Many, if not all, of these risk factors can be related to endocrine dysfunction, either as components of equine metabolic syndrome (EMS) or PPID.
Signalment and phenotype may give an indication of whether a horse or pony is at risk of laminitis, and whether EMS or PPID are likely to be present. However, clinical signs are an insensitive means of identifying horses at risk of laminitis, as subclinical endocrine disease is common and laminitis may be the first or only clinical sign.
Some animals that clearly exhibit clinical signs of PPID or EMS may not require endocrine testing to establish a diagnosis if owners can be convinced to implement appropriate management and/or treatment on the basis of clinical findings alone. However, most owners require a little more persuasion.
Typically, horses with EMS are overweight, but horses of normal appearance should also be tested for the condition as some animals without obvious adiposity can be hyperinsulinaemic and prone to laminitis12.
Owners have a skewed perception of the body condition of their horses. Up to 50% of the UK equine population is overweight, yet only 20% to 30% of owners will recognise their horses need to lose weight13,14. Many owners are reluctant to act on the knowledge their horses are overweight, hence demonstration of metabolic abnormalities may be helpful in encouraging dietary and management changes.
Debate exists over the best means of testing for insulin dysregulation, as gold standard techniques are not practical in clinical cases. Resting insulin levels are an insensitive means of detecting insulin dysregulation and challenge tests using orally or intravenously administered glucose (or insulin) are preferred.
Reliance on resting insulin levels will fail to detect large numbers of animals with insulin resistance and a tendency toward marked hyperinsulinaemia (and hence laminitis risk) following feeding. The use of an insensitive test is also counter-productive when trying to persuade owners management changes need to be made.
To avoid confounding the effects of feeding, tests for EMS should be performed after withholding food for a minimum of six hours. Typically, horses are given a haynet in the evening and then fasted overnight. Pain and stress may also result in hyperglycaemia and hyperinsulinaemia and testing of actively laminitic animals (for either EMS or PPID) should be postponed until they can walk comfortably.
Responses to oral glucose have become a popular means of testing for insulin dysregulation, even though they have not been validated against gold standard techniques.
The OST has the advantages of being quicker and not being dependent on the horse’s appetite for a feed full of glucose. However, it does require the horse or pony to be sufficiently compliant for a volume of sugar syrup to be syringed directly into the mouth. Intravenous tests are also possible, but are less convenient. A combined insulin glucose tolerance test has been evaluated as a test for insulin resistance17, but is not popular in ambulatory practice even though the test can be abridged or simplified. A simpler alternative is the two-step insulin response test18, which can be performed in just over 30 minutes.
Although PPID is an ageing-related disease, the age of onset is variable and a number of published reports show histologically confirmed disease in animals of 10 or younger19-22. Disease should, therefore, be considered, even if with a degree of scepticism, in younger animals with laminitis and the default position should be to test all laminitis cases for PPID. Laminitis is frequently the only clinical sign of PPID, especially in younger horses, so PPID should not be discounted in the absence of other clinical signs.
Measurement of a single resting adrenocorticotropic hormone (ACTH) concentration in a horse that is not overtly painful or stressed is a reliable means of detecting PPID16. However, it requires little extra time, work or expense to collect an additional ACTH sample 10 minutes after injection of 1mg of thyrotropin releasing hormone (TRH) in a “TRH stimulation test”31 (Table 2).
Assessing the pituitary response to TRH is considered to be the gold standard for diagnosing PPID and should be considered if resting ACTH samples are within 10pg/ml of the seasonal cut-off23 or if the risk of PPID is considered to be lower – that is, younger animals or animals with no clinical signs (and hence the risk of a false-positive diagnosis is higher). As it is minimal extra effort, it is hard to argue against the TRH stimulation test being performed as a first-line test for PPID.
The majority of horses with EMS (and many horses with PPID) are overweight and require an effective weight loss programme. Studies have demonstrated the effectiveness of dietary restriction in managing obese ponies, both in a controlled24,25 and, more recently, in a clinical setting26. Induction of weight loss by dietary restriction is accompanied by an increase in insulin sensitivity25,26.
Whether in people, horses or small animals, a critical factor, if not the critical factor, in the success or failure of any weight loss programme is the degree of contact with the medical professional overseeing the plan.
Frequent re-examination and re-evaluation of the progress of horses enrolled on weight loss programmes is therefore essential. Objective monitoring is important, not only for veterinary surgeons re-evaluating progress, but also as a means of empowering and motivating owners.
Measurement of bodyweight is a valuable means of assessing progress as there is limited correlation between weight loss and changes in body condition score (BCS). The use of weighbridges should be encouraged and portable devices are available that can be taken to owners’ premises (Figure 1).
If weighbridges are not available, weigh tapes provide a reasonable estimate of bodyweight and are objective (Figure 2). Repeated readings need to be comparable, therefore the same weigh tape should be used on each occasion, and it may be useful to clip a small mark into the coat so measurements are always taken from the same position.
Assessment of BCS is subjective and less reliable in obese animals24. Reliance on BCS can also be demotivating for owners, as considerable weight loss may be required before reduction in higher scores is observed. Morphometric measurements such as girth:height ratio, waist:height ratio and neck circumference are more useful27.
The aims of dietary management are twofold – firstly, to reduce energy content of the diet to facilitate weight loss and, secondly, to lower the non-structural carbohydrate content of the diet to reduce the glycaemic and insulinaemic responses to feeding that result in spikes of hyperinsulinaemia and hyperglycaemia. Any plan has to start with a gentle interrogation of the owner/carer to establish what is actually being fed. Invariably, it is far too much.
If the current diet contains excessive soluble carbohydrates, weight loss may be obtainable by simply removing concentrates and managing grazing carefully. Few native types will require anything other than forage and a vitamin/mineral balancer for general work. In good-doing types that are refractory to weight loss and in animals considered at risk of laminitis, strict dietary management will be required.
Hay should ideally be analysed and have a non-structural carbohydrate (NSC) content of less than 10%. However, in practice, few owners are prepared to have forage analysis performed for each batch they are feeding and it is rarely possible to find hay with an NSC content of less than 10%. When aiming for weight loss, hay is typically fed at 1.5% of the ideal bodyweight (as dry matter) and it must be weighed accurately on each occasion (Figure 3).
If no improvement is noted in weight and/or morphometric measurements after a month this can be reduced to 1.25% of the ideal bodyweight. Some native breeds of ponies, particularly Shetlands and Welsh ponies, are extremely resistant to weight loss and may need to have feed reduced to 1% of their ideal bodyweight per day28. When aiming for weight loss, the water-soluble carbohydrate (WSC) content of hay should be reduced by soaking it prior to feeding.
The percentage WSC loss increases with time, and rate of loss is higher at warmer temperatures, so hay should be soaked for as long as possible (preferably 12 to 16 hours) especially when ambient temperatures are lower29. Soaked hay should be well rinsed and fed immediately as soaking will result in proliferation of micro-organisms that may be deleterious to respiratory health, particularly in horses with recurrent airway obstruction.
Hay should be supplemented with a low calorie balancer to ensure adequate provision of protein, vitamins and minerals. The protein content of the balancer should be checked as some are little better than the forage itself.
To reduce the risks of detrimental gastrointestinal or psychological effects of reduced feed intake, feeding periods should be extended as much as possible using strategies such as:
Some horses with insulin dysregulation and laminitis are not overweight and some undergo effective weight loss programmes but remain hyperinsulinaemic, even after they have attained an appropriate body condition.
In these cases the aim is to prevent hyperglycaemia and hyperinsulinaemia without inducing further weight loss. This can be accomplished by feeding appropriate quantities of more calorie-dense, but low glycaemic, feeds in multiple small meals, such as non-molasses soaked sugar beet pulp or stabilised rice bran. If further energy is required, for example, in horses that are in high levels of work, then oil (maize, vegetable or flax seed) should be fed as an alternative to cereals.
Exercise facilitates weight loss when combined with dietary restriction and may increase insulin sensitivity. Overweight horses should be exercised as much as possible (laminitis permitting). At least 30 minutes of trot and canter exercise under saddle or on the lunge is recommended four to seven days a week, excluding time to warm up and cool down. Remedial farriery may be beneficial in facilitating a swift return to exercise.
Horses that have suffered from laminitis, or are considered at high risk of laminitis, are likely to require a period when they are denied access to pasture. A few very thrifty animals may always remain insulin-resistant despite effective dietary management and may need to be kept off pasture indefinitely. Nutritional intake is impossible to control in horses at pasture and daily requirements may be ingested within hours as speed of intake increases in response to less time at grass30.
Grazing muzzles can be effective in restricting intake. Providing short periods of access to grazing or strip grazing is beneficial in the majority, but is not without risk as rapid ingestion of grass may result in profound hyperglycaemic and hyperinsulinaemic responses. Turn-out into a ménage or an area of woodchip or sand is the most effective solution (Figure 4). While the set-up costs may be high the financial and welfare costs of poorly controlled EMS/PPID and recurrent laminitis may be just as unpalatable.
Once obesity and insulin dysregulation have improved, most horses can be returned to pasture gradually. However, care should be taken when sugar content is likely to be high during spring growth and frosty periods. Sugar content of grass is lower earlier in the day except during frosty periods.
Pharmacological intervention is no substitute for diet and management changes in EMS and in isolation is highly unlikely to have any appreciable effect. However, some clinicians use medication in the short term while management changes are taking effect, or in refractory cases when despite appropriate changes being made, laminitic episodes continue to recur.
The greatest value of some medications may be as a placebo that encourages owners to take other aspects of weight management seriously. However, other owners have a tendency to rely on medication and use it as an excuse to overlook the need for effective dietary restriction. Regular contact between the veterinarian and owner is important to ensure medication, if required, is being used appropriately.
Metformin is used in human medicine to increase tissue insulin sensitivity and control hyperglycaemia in diabetes mellitus. The efficacy of metformin as a treatment for EMS is questionable. An oral dose of 15mg/kg metformin did not improve insulin sensitivity in healthy ponies31, but metformin is thought to act locally at the intestinal level to limit postprandial hyperglycaemia and hyperinsulinaemia32.
Despite this potential benefit it is questionable whether metformin will have an appreciable clinical effect given its short duration of action. Its effects might just as easily be achieved by limiting the quantity of soluble carbohydrates being fed. To ensure the maximum treatment benefit, metformin should be administered 30 to 60 minutes before feeding. The recommended dose for metformin is 30mg/kg orally every eight to 12 hours.
Levothyroxine sodium is effective in inducing weight loss and improving insulin sensitivity in horses with EMS by imposing a state of hyperthyroidism and increasing metabolic rate33,34.
In the UK, levothyroxine is cost-prohibitive and rarely used. A plethora of nutraceuticals and supplements are marketed by feed and supplement companies for use in horses with EMS and laminitis; however, none have evidence of efficacy and their use cannot be endorsed.
PPID is an accepted risk factor for laminitis and a number of studies have reported a reduction in laminitis following treatment of PPID35-37. However, the quality of evidence provided by these studies is weak and prospective controlled trials are needed.
Few would deny the merits of treating confirmed PPID in horses with laminitis to reduce the risk of future episodes (Figure 5). Whether horses with endocrinological evidence of PPID, but no clinical signs, should be treated is more controversial. Although no evidence shows the use of pergolide prevents laminitis or the progression of PPID in horses, evidence is available of a protective effect in vitro38,39.
In the author’s opinion, treatment ought to be the default position pending the results of appropriate prospective research, as the only real downside is cost. Ultimately, it is an owner’s decision whether to invest in a treatment that may reduce the risk of laminitis.
The decision should also be made in the context of other risk factors for laminitis. If the animal is in good condition, is managed well and endocrine tests do not support the presence of concurrent insulin dysregulation, then a more relaxed attitude to treatment may be adopted.
Regular monitoring of these animals is important and dynamic tests of insulin dysregulation are preferred over resting tests, given the poor sensitivity of the latter. Withholding treatment for PPID may be a false economy as a year’s treatment with pergolide is unlikely to cost any more than a bout of laminitis that necessitates veterinary intervention.
Pergolide is the only licensed treatment for PPID and it is effective in the majority of cases. Treatments such as cyproheptadine and trilostane have little evidence to support their use and are generally regarded to be ineffective as monotherapy. Herbal treatments that contain chasteberry extracts (vitex agnus-castus) are marketed widely to horse owners; however, clinical evidence to support their use is limited to individual case reports.
In an independent study performed at the University of Pennsylvania, 13 of 14 horses treated with vitex agnus-castus deteriorated clinically and endocrinologically, only for nine of the 13 to then improve when subsequently treated with pergolide40.
The changes affecting the pars intermedia are diverse (PPID might be better regarded as a syndrome rather than a disease) with marked variation occurring between affected horses.
Monitoring is, therefore, imperative to ensure appropriate dosing. The licensed dose for pergolide varies slightly due to the fixed size of the tablets, but is close to 2μg/kg PO sid. The starting dose frequently needs to be adjusted based on follow-up clinical and endocrinological examinations generally performed a few weeks after treatment has started.
In a small minority of horses PPID cannot be controlled using pergolide alone and, in these cases, it is worth continuing treatment at the highest dose possible as, anecdotally, some horses may show a delayed response some months after the initiation of treatment. The highest possible dose may be governed by the development of side effects (generally inappetence), the financial limits of the owner or a daily limit of 10μg/kg, which is the maximum dose generally considered safe.
Anecdotal reports suggest cyproheptadine may be beneficial when a maximal dose of pergolide fails to result in sufficient clinical improvement. However, cyproheptadine is a similar cost to pergolide so few owners are willing to persevere once they reach the upper limit of pergolide treatment.
Once the horse is stable, clinically and endocrinologically, follow-up clinical and endocrinological examinations are recommended every three to six months.
Assessment of insulin dysregulation is also helpful in the monitoring of horses with PPID, particularly those with a history of laminitis, and should be performed as a routine.
Some horses may benefit from a higher dose of pergolide through the late summer and autumn months (August to October) when pars intermedia output increases and it is worthwhile factoring in tests for PPID and secondary insulin dysregulation at the beginning of this period.
Nutrition and general management should not be overlooked in horses with PPID (Figure 6). As horses with PPID are frequently hyperinsulinaemic the dietary and management advice appropriate for horses with EMS is also applicable and is critical in the prevention of laminitis.
Clipping, good farriery, anthelmintic treatment, early and aggressive treatment of infectious disease and routine dentistry are also important in horses with PPID.
The majority of cases of laminitis seen in practice are likely to be due to endocrine dysfunction – either PPID or EMS. Although our understanding of both syndromes is poor, if they are managed effectively the incidence of laminitis can be reduced dramatically.
While management is not difficult, ensuring client compliance can be, and regular clinical and endocrine reassessment and communication with owners are key to success.
