The Modern Equine Vet
March 2024
Vol 14 Issue 3 2024
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Managing Insulin Dysregulation

By Paul Basilio

When feeding horses with insulin dysregulation (ID), high-protein ration balancers have historically been the go-to treatment recommendation, despite the fact that the influence of dietary protein on disease control is not well understood.

Recent evidence, however, suggests that high-protein meals may actually exacerbate postprandial hyperinsulinemia in equids with ID, according to Allison T. Palmer, DVM, an equine internal medicine resident at The Ohio State University College of Veterinary Medicine. The new evidence is compelling enough to call into question the safety of this nutritional intervention in patients with ID.

Feeding the ID Equid
“Current recommendations for feeding horses with ID principally focus on 2 primary goals,” Dr. Palmer said during a presentation sponsored by Purina at the 69th Annual AAEP Convention in San Diego. “The first goal is to encourage weight loss where appropriate, and the second goal is to minimize postprandial hyperinsulinemia. The amount of hydrolysable dietary carbohydrates in the diet frequently is manipulated to achieve these aims.”

Most current dietary strategies for equine ID patients involve feeding low-nonstructural carbohydrate (NSC) forage and low-NSC, high-protein ration balancers to minimize the risk for trace mineral and vitamin deficiencies over time. NSCs include starch, monosaccharides like glucose and fructose, disaccharides and fructans, according to Dr. Palmer.

Pasture grass, cured hay and other forages can contain high levels of NSCs, which are associated with postprandial hyperinsulinemia.

“Most of the research effort [in this area] in humans is focused on the role of dietary protein and amino acids in improving systemic insulin sensitivity, encouraging weight loss, and improving gain of lean muscle mass,” Dr. Palmer said.

Different From Human Medicine
Several studies in human medicine have shown that high-protein diets in patients with type 2 diabetes mellitus result in significantly enhanced insulin secretion over time, independent of weight loss.

That’s great for humans who want to reduce their dose of exogenous insulin, but that’s not quite so great for horses with ID, where a principal therapeutic goal is minimizing hyperinsulinemia.

“Actually, the opposite is almost always the goal in horses,” Dr. Palmer explained. “We want to minimize this postprandial insulin secretion. Hyperinsulinemia is the most important risk factor for endocrinopathic laminitis.”

Equid-Centric Research
Despite the difficulties in extrapolating human studies to an equid population, relatively little attention has been given to the effect of dietary protein on insulin and glucose dynamics in equids. However, this is starting to become an active area of investigation for several research groups.

“While NSC appears to be a principal nutritional factor driving the equine postprandial response, high-protein meals have also been associated with exacerbated insulin responses in horses with ID,” Dr. Palmer noted.

One such equid-centric study found that when the insulinemic responses to a high-protein meal (31% crude protein fed at 4 g/kg) was fed to healthy horses and ID horses, there was a 9-fold greater insulin response in the ID horses over a 4-hour period.

Another study that’s currently in preparation for publication appears to echo these results. In that study, 7 metabolically healthy horses were fed a high-protein meal as part of a feed trial. Later, those same 7 horses underwent induction of experimental insulin dysregulation via 7 days of oral dexamethasone at 0.08 mg/kg. The feed trial was repeated while the horses were dysregulated.

“Those horses had a much more exaggerated insulin response when they were insulin dysregulated compared with their baseline state,” Dr. Palmer stated, adding: “These studies strongly suggest that high-protein ration balancers may exacerbate insulinemic responses in the setting of equine ID.”

Enter mTOR
When evaluating the role of feed in equine metabolic disease, Dr. Palmer said that it is important to understand that dietary protein and amino acids are robust activators of mechanistic target of rapamycin (mTOR) at the tissue level. mTOR plays a huge anabolic role in a horse’s response to nutrient ingestion, but prolonged mTOR activation can also cause local and systemic insulin resistance.

“mTOR activation has also been associated with changes in the epithelial phenotypes in horses,” Dr. Palmer said. “Activation of mTOR signaling has been demonstrated within the digital lamellae in horses subjected to experimental models of all 3 forms of equine laminitis: sepsis-related, hyperinsulinemia-associated and support-limb laminitis.”

The role of dietary protein and amino acids in laminitis does require further investigation, but she said that preliminary studies have validated the concern.

Clinical Next Steps
“When managing a patient whose insulin dysregulation is poorly controlled in the face of a low NSC diet, other aspects of the patient’s diet should be scrutinized to assess the influence on the animal’s persistent hyperinsulinemia,” Dr. Palmer explained.

She added a feed trial can be performed to evaluate the degree of postprandial hyperinsulinemia in response to certain components of the diet, including the ration balancer. This test can be done in a similar manner to an oral glucose test.

In 1 example, she said that a horse can be fed 1 flake of grass hay the night before the test and then muzzled afterward. In the morning, a baseline blood sample can be collected, and then the horse could be fed the specific dietary component (e.g., the ration balancer at the manufacturer’s recommended dose).

Additional blood samples can be drawn at 60 and 90 minutes (or longer) postprandially to determine the insulinemic response.

“If they have an exaggerated response, that could warrant modification of that portion of the diet,” she said. “Patients receiving high-protein ration balancers whose insulin dysregulation is currently poorly controlled should have this facet of their management critically evaluated.” MeV

For more information:
Loos CMM, et al. A high protein meal affects plasma insulin concentrations and amino acid metabolism in horses with equine metabolic syndrome. Vet J. 2019;251:105341.
Palmer AT, et al. Unpublished data. 2022.