Diagnosing Insulin Dysregulation & Equine Metabolic Syndrome

Diagnosis of insulin dysregulation can be a real challenge in equine practice. As our understanding of the underlying disease improves, we recognise the limitations of the currently available tests and reference ranges.

This document summarises some of the currently available information, which should help when selecting and interpreting laboratory tests in clinical practice.

The Equine Endocrinology Group (EEG) provides excellent information on this topic.

Collection tube requirements:

• Insulin, Triglycerides, Adiponectin: Serum tube
• Glucose: Fluoride oxalate tube

Resting insulin concentration

This is a convenient screening test. However, the test has a low sensitivity which means that a negative result does not rule out the presence of insulin dysregulation. A positive test result however, is really useful and confirms the presence of insulin dysregulation.

Fasting the horse prior to testing is no longer recommended as it further decreases the test sensitivity.

Resting insulin concentration should be measured to interpret the response to a horse’s ‘normal’ diet. It can be useful to try to measure insulin at its expected peak time, for example 90 – 120 minutes after feeding bucket feed, or pasture turnout. A single serum sample is needed for analysis.

Interpreting the result

< 20 iu/ml (LOW LIKELIHOOD OF ID)

A resting insulin concentration of less than 20 iu/ml is considered within an acceptable range, and the likelihood of ID is low. An oral Karo syrup test could still be carried out to further rule out insulin dysregulation. 

20 – 49 iu/ml (INCONCLUSIVE/SUSPECTED ID)

A resting insulin concentration in this range raises suspicion for insulin dysregulation, but a Karo syrup sugar test could still be useful to further evaluate insulin regulation.

>49 iu/ml (HIGH LIKELIHOOD OF ID)

A resting insulin concentration in this range confirms the presence of insulin dysregulation. No further testing is needed. 

Oral sugar tests

By challenging the horse with oral sugar, a better evaluation of insulin function can be made. The simplest way to do this is to feed the normal concentrate ration of the horse and measure insulin concentration 2 hours after. Although less standardised, this gives a good idea of what insulin levels are occurring in response to a horse’s normal diet.

Alternatively, a sugar challenge can be provided by feeding Karo Light Corn syrup or dextrose powder. Karo Light Corn syrup is generally considered the easiest as it is most palatable and doesn’t rely on the horse eating the powder.

Recommended test:

Karo Light corn syrup test: 

• Fast horse for 3-6 hours before testing. Practically, a small amount of hay can be given to the horse the evening before, and testing carried out the following morning.
• Administer 0.45mls/kg Karo Light corn syrup orally by dosing syringe. This can be purchased at www.amazon.co.uk or in some supermarkets. A lower dose of 0.15ml/kg dose of Karo Light syrup can also be used.
• Collect a blood sample at between 60 and 90 minutes after dosing, for measurement of insulin and glucose.

The following table summarises the currently recommended cut-offs for the Tosoh AIA-900 analyser at Rossdales:

More involved tests can be carried out to assess insulin sensitivity such as the insulin tolerance test. This test involves administration of intravenous insulin. The protocol can be found on the EEG website.

Other markers for Equine Metabolic Syndrome

Triglyceride concentration

Horses with insulin dysregulation and obesity can have hypertriglyceridemia. This has been shown to have some correlation with insulin risk. Hypertriglyceridemia can also be a side effect of treatment with the SGLT-2 inhibitors. Measurement is recommended as part of the monitoring process in horses undergoing treatment with these drugs but can also be useful as part of initial screening.

Adiponectin

There is a great deal of interest in measuring the cytokines that are released from adipose tissue as a marker of Equine Metabolic Syndrome. Adiponectin is an anti-inflammatory cytokine that has a role in glucose regulation. High molecular weight adiponectin accounts for the majority of circulating adiponectin and its concentration is inversely proportional to body condition score and insulin concentration.

Early studies failed to correlate adiponectin with insulin concentration and laminitis risk. However, more recent work has shown a greater association between high molecular weight adiponectin concentration and laminitis risk. However, more recent work has shown a greater association, and low adiponectin has been suggested to play a role in insulin dysregulation and has been associated with an increased risk of laminitis.

While measurement of adiponectin may be helpful in individuals suspected of having metabolic disease, this is not recommended as a first line test and additional evaluation of insulin dysregulation is required to further assess metabolic dysfunction and laminitis risk. Total adiponectin measurement is currently available in the UK.

A good summary for further reading is:

The diagnosis of equine insulin dysregulation, Bertin FR, de Laat MA, Equine Vet J 2017 Sep;49(5):570-576

ECEIM consensus statement on equine metabolic syndrome
Andy E. Durham, Nicholas Frank, Cathy M. McGowan, Nicola J. Menzies‐Gow, Ellen Roelfsema, Ingrid Vervuert, Karsten Feige, Kerstin Fey

J Vet Intern Med. 2019 Mar-Apr; 33(2): 335–349.  Published online 2019 Feb 6. doi: 10.1111/jvim.15423

Further information

ACTH and Insulin in Equids – the significance of the analytical method.

References: 

1. Bamford NJ, Potter SJ, Harris PA, Bailey SR. Effect of increased adiposity on insulin sensitivity and adipokine concentrations in horses and ponies fed a high fat diet, with or without a once daily high glycaemic meal. Equine Vet J. 2016; 48:368-73
2. Dunbar, LK, Mielnicki, KA, Dembek KA, Toribio RE and Burns TE. Evaluation of Four Diagnostic Tests for Insulin Dysregulation in Adult Light-Breed Horses. J Vet Intern Med 2016;30:885–891
3. Eiler H1, Frank N, Andrews FM, Oliver JW, Fecteau KA. Physiologic assessment of blood glucose homeostasis via combined intravenous glucose and insulin testing in horses. Am J Vet Res. 2005 Sep;66(9):1598-604.
4. Frank N, Geor RJ, Bailey SR, Durham AE and Johnson PJ (2010). Equine metabolic syndrome, Journal of Veterinary Internal Medicine 24(3): 467-475.
5. Frank, N. (2011) Equine metabolic syndrome. Vet. Clin. N. Am.: Equine Pract. 27, 73-9
6. Jocelyn NA, Harris PA and Menzies-Gow NJ (2017). Effect of varying the dose of Karo Light syrup on the insulin response to the oral sugar test, Havemeyer Foundation International Equine Endocrine Summit, Miami.
7. Manfredi J, Geor R, Weber PS, Norby B and McCutcheon J (2016). Evaluation of an oral sugar test for dynamic assessment of five equine breeds’ insulin response/sensitivity, Journal of Veterinary Internal Medicine 30(4): 1,510-1,511.
8. Menzies-Gow NJ, Harris PA, Elliott J. Prospective cohort study evaluating risk fac- tors for the development of pasture-associated laminitis in the United Kingdom. Equine Vet J. 2016; 49:300-6
9. McGowan CM, Olley RB and Carslake HB (2017). Sensitivity and specificity of fasted basal insulin compared to dynamic testing in horses and ponies with suspected equine endocrine disease, Havemeyer Foundation International Equine Endocrine Summit, Miami.
10. Smith S, Harris PA and Menzies-Gow NJ (2015). Comparison of the in-feed glucose test and the oral sugar test, Equine Veterinary Journal 48(2): 224-227.
11. Rendle DR, Laboratory diagnosis of the endocrine causes of laminitis Livestock July/August 2017, Volume 22 No 4
12. Tadros, E.M. and Frank, N. (2013) Endocrine disorders and laminitis. Equine Vet. Educ. 25, 152-162.