Hyperinsulinemia is an important risk factor for laminitis in horses. Identifying insulin-resistant horses is key to preventing and managing laminitis. At the 2024 Tex Cauthen Farrier/Veterinarian/Researcher Seminar in Kentucky, Andrew van Eps, BVSc, PhD, MACVSc, Dipl. ACVIM, professor at University of Pennsylvania’s New Bolton Center, proposed multiple ways to evaluate a horse’s insulin levels.
A Closer Look at Adiponectin
Adiponectin (high molecular weight) is a protective adipokine from fat cells that improves insulin sensitivity and serves as a metabolic health marker. It is insulin-sensitizing and acts as an AMP-activated protein kinase (AMPK) agonist to inhibit mTor (which promotes the activation of insulin receptors and insulin-like growth factor receptors). Adiponectin might also protect tissues against cell stress—both endoplasmic reticulum and oxidative—and ischemia. Low serum adiponectin is associated with insulin dysregulation. It is also an independent risk factor for laminitis when its levels are low.
Adiponectin doesn’t fluctuate with stress or feeding. Researchers have compared adiponectin levels in horses fed carbohydrate or fat-based diets for more than 20 weeks. Horses in both categories developed high leptin levels, but only the carbohydrate-fed horses developed insulin dysfunction (ID) along with low serum adiponectin.
Veterinarians can evaluate baseline fed insulin as a random test in nonfasted horses. This test involves taking blood samples two hours after feeding or pasture access. It is a reasonable predictor of insulin dysregulation. Insulin levels of 25 mIU/ml are 80% sensitive and 85% specific for ID.
Van Eps reported that a combination of high insulin and low adiponectin is a red flag. Normal insulin and low adiponectin is a warning sign, but it is possible that a single sample doesn’t account for insulin fluctuations throughout the day. Doing a sugar or feed challenge might identify hyperinsulinemia with a potentially higher risk of laminitis. It is important to monitor and screen these horses.
Attempts to increase adiponectin through diet and exercise are not particularly helpful, especially because certain breeds are inherently at risk for low adiponectin, including Welsh ponies and donkeys. Thoroughbreds have a lower risk. Sick and hospitalized horses with laminitis reportedly also have low adiponectin levels.
Treating Hyperinsulinemia in Horses: Diet Is Key
Dietary changes, along with exercise and pasture management, are critical to controlling hyperinsulinemia in horses. Besides feeding forage with < 10% nonstructural carbohydrates (NSC), van Eps emphasized the benefits of soaking hay to reduce sugars and starches in the feed. Study results indicate soaking grass hay in five gallons of room-temperature water for up to two hours provides the maximum benefit for controlling sugar and starch levels. Alfalfa is lower in NSCs than grass hay, but soaking alfalfa is also helpful.
The European College of Equine Internal Medicine offers guidelines for dietary control of obesity in horses, which is a risk factor for insulin dysregulation. Rather than feeding horses 2% of their bodyweight in forage, owners can feed 1.4-1.7% of their bodyweight to achieve weight loss. These horses should not eat supplementary feeds. Exercise can also help horses lose weight.
Medications to Control Insulin
Van Eps described available medications for controlling insulin levels in horses:
- Levothyroxine might assist with weight loss and insulin sensitivity.
- There is no good evidence to support the long-term use of metformin, although it might have a targeted effect when administered at feeding time. It has poor oral bioavailability (4-7%) in horses.
- Pergolide is useful for managing confirmed pituitary pars intermedia dysfunction.
- Sodium glucose cotransporter-2 (SGLT-2) inhibitors help horses eliminate glucose through their urine. Currently, ertugliflozin (Steglatro) provides the most encouraging results, but it’s use is off label.
- Semaglutide (Ozempic) is a glucagon peptide-1 (GLP-1) agonist mimetic shown to improve insulin responses to oral sugar testing in horses. Side effects include slow gastric emptying and slowed intestinal motility, which are risk factors for colic.
- Pioglitazone (high molecular weight, HMW) might improve adiponectin increases over time. It blocks a specific cell receptor to facilitate growth of insulin-sensitive fat cells, which also produce adiponectin. This might be a slow way to control insulin, but van Eps noted it’s much less expensive than SGLT-2 inhibitors.
Researchers evaluated pioglitazone’s effects on adiponectin concentrations and insulin responses after the oral sugar test. Fifteen horses and ponies received 2 mg/kg orally of HMW pioglitazone once daily for 28 days. The subjects were grouped into horses, ponies, and insulin dysregulated (ID) animals. Oral sugar tests were performed before and after treatment to measure adipokines on Days 0, 14, and 28. The researchers measured insulin and glucose levels on Days 14 and 28. The results indicated significant decreases in insulin responses to the oral sugar test at 90 and 120 minutes, especially after pioglitazone treatment in the ponies and insulin-dysregulated individuals. “Adiponectin concentrations were significantly increased in all groups after pioglitazone treatment,” the authors stated. They concluded that this medication provides positive effects for treating metabolic derangements in horses with ID and equine metabolic syndrome.
Reference
Legere RM, Taylor DR, Davis JL, et al. Pharmacodynamic Effects of Pioglitazone on High Molecular Weight (HMW) Adiponectin Concentrations and Insulin Response After Oral Sugar in Equids. J Equine Vet Sci. Nov 2019; DOI: 10.1015/j.jevs.2019.102797
Related Reading
- Management of Hyperinsulinemia and Laminitis With Ertugliflozin
- The Effect of High Protein Diet on Insulin Dysregulated Horses
- The Effects of Adiposity and Weight on Equine Performance
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