Laminitis Research: Equine Insulin Resistance Does Not Respond to Metformin Medication; Diet and Exercise Remain Key to Laminitis Prevention

Researchers in Australia tested the effects of a human medication, metformin, on ponies with insulin resistance, a condition that puts horses at risk for developing the endocrine or metabolic form of laminitis. The medication had no effect. (J.A. Holland image)

New research on the pharmacological management of the condition of insulin-resistance in horses and ponies has suggested that diet and exercise are still key in any management plan.

Insulin resistance (IR) is defined as the diminished ability of a given concentration of insulin to exert its normal effect on glucose dynamics in particular. This causes the body to keep releasing more and more insulin in order to elicit an effect. This may be one of the most predictable factors that determines whether a horse or pony could be more susceptible to what is commonly known as the "endocrine" or "metabolic" form of laminitis.

The University of Minnesota College of Veterinary Medicine's Equine Genetics and Genomics Laboratory explains insulin resistance this way:

Insulin  is a hormone involved in the regulation of glucose (sugar) levels in  the blood and tissues of the body.  In response to feeding, insulin is  secreted by the pancreas into the blood stream. Insulin in the blood  stream directs the glucose (sugar) absorbed from the food into the  body’s tissues including liver, fat and muscle.  Insulin resistance  occurs when insulin no longer has a normal effect on the tissues. In the  insulin resistant horse, the pancreas releases insulin into the blood  stream, and the insulin arrives at the tissues and binds the cells,  however the glucose enters the tissue cells at a much lower rate than  normal. This lower rate of glucose uptake into tissues results in higher  levels of blood glucose.

Horses and ponies compensate for  insulin resistance by secreting even more insulin into the bloodstream  in order to keep the blood glucose concentration within the normal  range.  Therefore, horses and ponies with EMS (Equine Metabolic Syndrome) have a higher  concentration of insulin within the blood, which can be measured to  determine if insulin resistance is present.

An important goal for owners and vets should be to prevent IR from developing, or to manage it before it contributes to the development/progression of other potentially life-threatening conditions. While the correct management of energy intake and exercise levels is thought to be essential, in some cases medication is also considered, especially when increased exercise is not possible. With no licensed drugs currently available for the treatment of IR in horses and ponies, off-label medications used for IR in humans are sometimes prescribed.

A trial was conducted by the School of Animal and Veterinary Sciences at Charles Sturt University in New South Wales, Australia and the Department of Clinical Studies at the University of Pennsylvania's New Bolton Center, in collaboration with the Waltham Equine Studies Group in Great Britain.

The study's intention was to confirm the positive effect of the human medication metformin on insulin and glucose dynamics in insulin-resistant ponies so that this treatment could be used as a positive control in other studies.

Glenys Noble BAppSc(Equine Studies) PhD, along with PhD candidate Kellie Tinworth BSc(hons) MSc, carried out the clinical trial in Australia. Six insulin resistant, non-obese ponies were repeatedly monitored by means of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin ia a drug reported to enhance insulin sensitivity of peripheral tissues in humans without stimulating insulin secretion. It was administered twice-daily (15mg/kg BW BID) to three of the ponies for 21 days.

Meanwhile, the three remaining ponies formed a control group, and each received a placebo. After a wash-out period, the treatments were crossed over.  A Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) was conducted to evaluate the level of insulin resistance before and after each treatment.  The ponies' body weight, body condition score and cresty neck score were also assessed. They did not change during this study.

Ray Boston MSc PhD is Professor of Applied Biomathematics in Clinical Studies at the University of Pennsylvania's New Bolton Center. He analyzed the data using MinMod, a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test, and Stata 10.1 statistics analysis software. No change in insulin sensitivity or glucose dynamics was seen under the control conditions or in response to the dose of metformin given in this study to these ponies.  

What does this study mean to horse owners? Clare Barfoot RNutr is the research and development manager at the British feed company Spillers®; she reviewed the research and said: “Although clinical trials with metformin are ongoing, this trial was consistent with our previous work showing that the bioavailability of metformin in horses is poor, and chronic dosing at these levels may not achieve therapeutic blood concentrations.”

She continued: “On this basis it would seem that a fiber-based diet that is low in starch (found in cereals) as well as  (being low in) sugar and fructans (found in grass), in conjunction with regular exercise if possible, is still the safest and most effective way to manage insulin-resistant ponies. It is important to recognize that, even if other doses of metformin are shown to be beneficial in the future for certain sub-groups of animals, full consideration to diet and management should remain a key tactic.”

The Waltham® Equine Studies Group, headed up by Dr Pat Harris MA PhD, VetMB DipECVCN MRCVS, provides the scientific support for the Spillers® and Winergy® brands sold in Great Britain.

To learn more: K. D. Tinworth, R. C. Boston, P. A. Harris, M. N. Sillence, S. L. Raidal, G. K. Noble (In press). The effect of oral metformin on insulin sensitivity in insulin-resistant ponies The Veterinary Journal; Available online 23 February 2011, doi:10.1016/j.tvjl.2011.01.015.

Thanks to Spillers for sharing this information with Hoofcare and Lameness.

© Fran Jurga and Hoofcare Publishing;  Fran Jurga's Hoof Blog is a between-issues news service for subscribers to Hoofcare and Lameness Journal. Please, no use without permission.  You only need to ask. This blog may be read online at the blog page, checked via RSS feed, or received via a digest-type email (requires signup in box at top right of blog page).  To subscribe to Hoofcare and Lameness (the journal), please visit the main site, www.hoofcare.com, where many educational products and media related to equine lameness and hoof science can be found.  Questions or problems with this blog? Send email to blog@hoofcare.com. 

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Gustav vs Louisiana: Picking Up the Pieces

Radar screen of a hurricane-tracking plane, courtesy of NOAA archives.

The news crews are pulling out of Louisiana, now that Gustav is gone. They are labeling it a blow-over, but was it really?

Back in 2005 when Katrina hit, farrier Dick Fanguy was supposed to be at home in bed recovering from back surgery, but instead reported to work at the Louisiana State University horse triage station at the showgrounds...and stayed there for weeks, shoeing horses and treating wounds and helping the vets.

He checked in here on Sunday, saying he had been in touch with the vets, and was ready to hunker down until it passed. He'd report to work if they needed him. He ended up hunkering way down. His friend Danvers reported this afternoon that Dick exited his house near Baton Rouge with the help of a chainsaw, as all the trees surrounding his house had come crashing down. (Dick's advice: Bring the chainsaw into the house before the storm hits. You might need it to get out.)

It's not over for Dick.

Further south, Molly the (Amputee) Pony's barn is partially flooded, with plenty of roof damage. Her owner is still living in a FEMA trailer from Katrina, and you can imagine her concern as a tree almost toppled on the construction site of her unfinished replacement house.

It's not over for Kaye and Molly.

No doubt more stories will be heard as the power returns and people can communicate better. Just remember that a storm is a storm, even when CNN is disappointed that it wasn't a bigger story or when FEMA wants to take credit for an evacuation well-orchestrated. Maybe Hanna or Ike will be better for broadcast ratings, but any storm, anywhere, is a danger to people and animals.

The lights may be back on in New Orleans' French Quarter by tomorrow night. But the people out in the countryside may have to sit and wait a while (in the dark) before they can tell us what happened or send photos. It may not be over yet, for them.

Laminitis Research from the Field to the Feed Room

Research by Bridgett Byrd (M.S., PhD candidate) at Virginia Tech, was used to create this graph. It shows that pastures at certain times of year have specific times of the day when plants contain high levels of non-structural carbohydrates (NSC). This is effectively mirrored by the insulin concentrations of the horses grazing on such pastures, in a similar way to the feeding of high starch and sugar diets. While this research has been available for the past few years, many horses owners have not been informed of the cumulative effects of long-term high-sugar diets on horses, particularly on sedentary recreational horses. (Graph and caption credit Virginia Tech.)

Remember the image in that graph. We have just turned the calendars to March, so spring will soon be here and the time is here to start planning how horses will be managed on spring grass.

This year, thanks to increased educational efforts, many horse owners are seeking advice on how to avoid laminitis caused by spring grazing. Many horses suffer annual bouts of laminitis that can adversely affect the horse’s soundness for months, or may develop into serious chronic laminitis with its many problems.

Nutritional experts, however, caution that laminitis and insulin resistance are year-round problems and that a horse's entire feeding program should be scrutinized, not just the turnout on pasture.

The Waltham® Equine Studies Group, led by Dr Pat Harris MA PhD, VetMB DipECVCN MRCVS, offers this summarized explanation: “Turning certain ponies out onto lush pasture in the spring and autumn is a common triggering factor for the development of laminitis. It is currently thought that high levels of water soluble carbohydrates, (which include simple sugars as well as Fructan – the more complex storage carbohydrate) – and/or starch may be involved in this process.

"Previous research carried out in collaboration with Virginia Tech by the Waltham® Equine Studies Group in 2004 confirmed a link between insulin resistance and laminitis. This work demonstrated that a high starch and sugar diet, that causes corresponding peaks and troughs in glucose and insulin, increases the degree of insulin resistance.

Dr Harris continues: “The new revelations linking pasture directly to the potential risk of insulin resistance have important consequences for certain horses and ponies prone to laminitis and tying up, as well as obese animals that will already have a greater degree of insulin resistance. For these animals it is likely to be safer to feed alternative sources of forage at key times of year.”

Last month, Florida-based Seminole Feeds announced that it would no longer be the US distributor for Spillers brand feed products, which are developed with Waltham research principles. “Happy Hoof”, a high-fiber alternative to high-sugar hay, was one of the products sold by Seminole in the USA. Seminole has launched a new line of low-starch feeds under its “Wellness” label.

Hoofcare and Lameness does not have much information at present for horse owners "orphaned" by the dearth of Spillers products in the USA.

Maine-based Lucerne Farms, makers of the Dengie product lines of alfalfa-based chopped hay in the USA, is now offering high-fiber, low-sugar products for horses at risk for laminitis. The company also offers excellent customer support.