Testing for Insulin Dysregulation

Insulin dysregulation (ID), which includes insulin resistance and abnormally high levels of insulin in the blood (hyperinsulinemia), is a known cause of endocrine-associated laminitis, as well as an underlying cause of equine metabolic syndrome that leads to obesity often characterized by fat pads and cresty necks. Testing for these conditions remains a challenge, so researchers from the Universities of Queensland and Melbourne examined the relative utility of three diagnostic tests for diagnosing ID and identifying horses with underlying laminitis.

A total of 146 healthy Welsh and Shetland ponies were recruited into the study, tested for ID using three different blood tests (baseline insulin levels, insulin levels after an oral dose of sugar and an insulin resistance test that involves measuring sugar levels after injecting a dose of insulin). The ponies were also examined for the presence of laminitis. The testing identified 79 of the 146 ponies as affected by ID. Used individually, none of the three tests identified every case of ID. Baseline insulin testing alone missed 86% (68/79) of the cases, the oral sugar test missed 43% (34/79) and the insulin resistance test missed 14% (11/79). While a pony with a high baseline insulin level would likely have ID, a normal insulin level would not necessarily rule out ID. Only running both the oral sugar test and the insulin resistance test together has a high probability of identifying every case.

—Clark BL et al. The Vet J 2023;106019

A Feed Supplement to Lower Insulin Levels

Faculty at the University of Copenhagen in Denmark conducted a cross-over trial of a commercially available prebiotic feed supplement containing oligosaccharides (OS) to evaluate its effects on insulin dysregulation in horses with equine metabolic disease. It is believed that obesity results in changes in the gut microbiota. This in turn causes dysfunction at the intestinal barrier resulting in increased circulating endotoxins and systemic inflammation.

Eleven privately owned horses and four ponies (seven mares and eight geldings) showing signs of obesity and cresty necks typical of equine metabolic disease and insulin dysregulation were included in the study. All the horses rotated on and off either the supplement or a placebo for two 6-week periods with a 2-week washout period in between. Blood samples were analyzed using an oral sugar test before and after each treatment period measuring insulin, endotoxin, glucose and amyloid levels, and fecal samples were analyzed to measure the relative populations of bacteria present.

The supplement appeared to reduce circulating insulin levels in geldings but not mares. There was also a tendency toward a reduction in the types of gut bacteria associated with obesity in the treatment groups. The authors concluded that OS supplements may be a promising treatment for insulin dysregulation and equine metabolic syndrome, but more work is needed to better understand if there are important differences between geldings and mares.

— Skiödebrand E et al. Osteo Cart Open 5 2023:100381

Diabetes Medications for Insulin Dysregulation

Two studies examined the safety and efficacy of medications called sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of drugs commonly used for the treatment of type-2 diabetes in humans as a treatment for insulin dysregulation (ID). ID, also called insulin resistance, is characterized by high levels of insulin in the bloodstream or hyperinsulinemia (HI). ID is a characteristic of equine metabolic syndrome which commonly causes obesity and laminitis in ponies and horses.

The first study, conducted with 22 ponies in Queensland, Australia, included 12 ponies treated with velagliflozin and 10 controls treated with a placebo. After 16 weeks of daily treatments, ponies that received the drug had decreased circulating insulin levels in response to a high glucose dietary challenge. In addition, the circulating insulin levels before the challenge had decreased to below the threshold associated with an increased risk of laminitis. These responses were reversed 4 weeks after the end of the treatment trial when the medication was withdrawn. No weight loss or decreases in body condition or cresty neck scores occurred in the treatment group or control groups. No side effects were noted throughout the study including excessively low glucose levels, which were a potential concern.

The second study, a case series with no controls or sham treatment group, was conducted by the Equine Cushing’s and Insulin Resistance Group, an Arizona non-profit group dedicated to improving the management and welfare of horses with equine Cushing’s disease and equine metabolic syndrome. Ten horses with HI that had not responded to dietary management or treatment for equine Cushing’s disease were treated with canagliflozin (Invokana), another SGLT2 medication used for diabetes in humans. Some of the horses were concurrently being treated with pergolide for equine Cushing’s disease, as well as thyroid supplementation. The medication was given orally once per day, and many of the horses were followed for several months.

All the treated horses responded with a substantial decrease in serum glucose and insulin concentrations to normal or near normal levels. Also of great interest is that laminitis pain when present resolved in all cases, animals lost excess weight and there was a notable decrease in fat deposits including those typical of a cresty neck. These clinical improvements are especially hard to achieve with dietary management alone. No serious side effects were noted throughout the treatment period.

The authors emphasize that concurrent dietary management and treatment for equine Cushing’s disease must be continued if indicated along with treatment with canagliflozin. The authors suggest that this expensive treatment should be reserved for refractory cases. However, these results are encouraging and warrant further research to document safety, efficacy and long-term effects.

— Meier A et al. BMC Vet Res 2019;15:65 and Kellon EM