Abnormally high insulin is a key feature of Equine Metabolic Syndrome and responsible for the high laminitis risk but there has been considerable uncertainty regarding the best way to test for abnormal insulin.
The earliest suggestion was to fast the horse or pony before testing insulin level. This seemed to make sense since humans are fasted before diabetes testing. However, horses are not humans. Equine Metabolic Syndrome is not the same as Human Metabolic Syndrome or human type II diabetes.
It became evident that many horses and ponies with metabolic syndrome were testing negative after fasting. Part of this was because horses do not typically maintain high glucose and insulin levels when fasted in the way many metabolic syndrome humans do. An even bigger problem was what was being called “normal”.
To be a positive result, a threshold of 20 uIU/mL for a fasting insulin (aka basal insulin) was set. If below 20 uIU/mL, the test was considered negative. However, a review of reported equine insulin levels in published studies and PhD dissertations shows a level of 20 uIU/mL is more typical of a normal response to a grain meal than fasting. This high threshold resulted in a high percentage of the animals classified as positive on the test being correctly diagnosed (high specificity) but a very large number of cases were miscategorized as normal (low sensitivity).
Various challenge tests were then devised to pick up cases missed by fasting insulin. These included grain, Karo syrup feeding or glucose powder in a high fiber meal. They are more time consuming, more expensive and not without risk. Another approach would be simply to have a more accurate threshold.
Olley et al (2019) did exactly that. They compared the fasting insulin levels of 62 horses and ponies with results of a CGIT – combined glucose and insulin test. The CGIT is an intravenous test for insulin resistance. They determined the upper limit of normal for a fasting insulin should be 5.2 uIU/mL – not 20! The authors pointed out that the problem wasn’t that insulin is a poor test; it was the cutoff that was to blame.
The findings aren’t a surprise to anyone familiar with the many other prior studies looking at equine insulin. The 5.2 uIU/mL ceiling is in line with previous reports. However, one problem with using fasting insulin as a screening test is that many assays may not be reliable at these low levels.
The Equine Cushing’s and Insulin Resistance Group, http://www.ecir.groups.io, has never recommended using fasting insulin because of the large number of incorrect results with the 20 uIU/mL guideline and because high insulin occurs as a response to what is eaten. It stands to reason that insulin after a bucket of sweet feed won’t be the same as after munching hay or not eating at all for an extended period. Olley also pointed out insulin “normal” ranges have to be defined by the feeding situation.
ECIR recommends testing horses with access to known low sugar/starch hay or pasture from the night before, overnight and on the day of testing. Insulin and glucose are tested. The glucose:insulin ratio and insulin resistance proxies of RISQI and MIRG, as defined by the work of Dr. Treiber’s group (2005, 2006), are used to classify the horses and ponies. ECIR has a calculator on their information site which can compute the proxies for you: https://www.ecirhorse.org/ir-calculator-leptin.php . Cornell’s diagnostic laboratory is recommended as they use the same methodology for testing insulin as the original work.
The proxies ECIR uses have been developed from what is universally recognized as the “gold standard” in insulin resistance testing, the FSIGTT – frequently sampled intravenous glucose tolerance test. They were then field tested on ponies living at pasture, with no fasting before testing. The pretest feeding protocol was designed to mimic that.
For more background visit http://www.ecirhorse.org.
Eleanor Kellon, VMD