Equine metabolic syndrome (EMS) (Atypical Cushing’s disease, peripheral Cushing’s disease)
Introduction
EMS results in significant peripheral insulin resistance; the exact etiology is unknown. It tends to be seen in horses <10 years. EMS is a syndrome of obesity, insulin resistance (IR) and laminitis. Obesity is not a significant factor on its own and appears to be strongly linked to genetic predisposition especially in some of the susceptible British breeds of ponies. Clinical signs include recurrent laminitis that is often seasonal, PuPd and abnormal weight distribution (including ‘cresty’ neck). Hirsutism, abnormal coat shedding and sweating are not usually found in EMS and this helps in the differentiation with PPID. Basal cortisol levels are normally significantly increased above the reference range. Insulin levels are frequently raised but there is considerable variation over a 24 hour period. Endogenous ACTH is expected to be within the normal range or borderline high. Animals test negative on an overnight dexamethasone test, so this is the test of choice to differentiate EMS and PPID. Basal cortisol and insulin may also be useful.
The suggestion of EMS is obtained by measuring insulin and cortisol at 2 or 3 spaced 4 hourly samples in a day, ideally 8am, 12pm (midday) and 4pm to really demonstrate persistent insulin resistance. If only 1 sample is to be done 12pm (midday) is the most important, high valueswithout having fed a carbohydrate meal are likely to be caused by insulin resistance.
In EMS there are some factors present that can be assessed and these consist of obesity, insulin resistance (IR) and dyslipidaemia as the most readily available. Further components such as blood pressure, uric acid or adipokines may also be helpful and further investigation will establish whether of significant value.
Obesity estimates/measurements
In most cases this is subjective with visual assessment or the use of body condition scoring. More objective measurements may be obtained with the use of ultrasonography or morphometric measures, for example girth, rump width.
Resting hyperglycemia
High glucose is not a common finding in cases of EMS. However it is advisable to record it in all cases to pick up the occasional case of type II diabetes mellitus that may occur.
Hyperinsulinaemia
Insulin levels are usually raised on basal samples, but if there is doubt, a dynamic test of insulin resistance can be used, for example, the combined glucose-insulin test. Ensure the horse is fasted or not fed any carbohydrate prior to collection of samples and the horse has not exercised that day. Elevated insulin values without having fed a carbohydrate meal are likely to be caused by insulin resistance.
Although high insulin suggests IR, low insulin does not rule out IR. Many IR cases are only detected when excessive endogenous insulin is secreted in response to oral or i/v glucose and/or delayed return to normal glucose levels following a glucose challenge (consistent with glucose intolerance).
Combined insulin-glucose tolerance test (CGIT)
- Fast the patient overnight
- Measure basal glucose and insulin
- Give 150mg/kg 40-50% glucose solution i/v immediately followed by 0.1IU/kg soluble insulin
- Collect samples for glucose at 1, 5, 15 minutes, then every 10 minutes up to 45 minutes, then every 15 minutes up to 2.5 hours
- Test the 45 minutes sample for insulin
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Interpretation
Normal horse: the peak blood glucose occurs around 1-5 minutes and reaches 2-2.5 x baseline. The blood glucose usually remains above baseline for between 30-45 minutes, followed by a negative phase for a further 1-2 hours where the blood glucose is below the original baseline.
IR case: this is expected to have a higher peak and a longer positive (>45 minutes) and shorter negative phase (sometimes there is no negative phase). A 45 minute insulin concentration of >100IU/l also implies IR.
NB that this test is NOT popular as requires hospitalisation and frequent sampling.
In-feed oral glucose challenge test
This test can be performed at the stable premises and is useful in suspected IR cases with normal fasted insulin concentrations:
- Fast the patient overnight (12 hours)
- Request owner to give a nonglycaemic feed (chaff) containing 1g/kg glucose or dextrose powder (wet the feed to facilitate mixing and ingestion)
- Blood sample for insulin 2 hours post consumption of the feed
Interpretation
Serum insulin >85IU/l in the 2 hour sample is indicative of IR.
Dyslipidaemia
Increased serum triglycerides are suggestive of obesity and IR. For opinions on the use of insulin to glucose ratios and derivatives thereof then please refer to: Treiber et al. 2006.
The article by Frank et al. 2010 does not appear to consider these any more accurate than the tests listed above for diagnosing EMS.