diagnosing insulin dysregulation in horses

As many as 89% of horses with the hoof disease laminitis develop this painful condition because of insulin-related endocrine disorders, so it’s important to monitor for these problems and make diagnoses early. Time of year can impact blood-insulin levels, though, complicating diagnosis for other endocrine diseases, such as pituitary pars intermedia dysfunction (PPID, equine Cushing’s disease). So a University of Kentucky (UK) research group recently analyzed how season affects one type of endocrine test and visual indicators that could help veterinarians make a diagnosis.

Erica Macon, MS, a PhD candidate under Amanda Adams, PhD, at UK’s Gluck Equine Research Center, in Lexington, examined seasonal effects on morphometric—that is, body shape and size—measurements and insulin responses to the oral sugar test (OST) in horses with and without abnormal blood insulin levels (known as insulin dysregulation, or ID) in control and ID horses. She presented her results at the 2018 American Association of Equine Practitioners Convention, held Dec. 1-5 in San Francisco, California,

The specific measurements she and her team considered were body weight, body condition score (BCS), and cresty neck scores.

At the start of the study, Macon and her colleagues examined the endocrine history, insulin levels, and adrenocorticotropic hormone (ACTH) levels of 22 horses in their mid- to late-teens—11 horses with ID and 11 horses without ID.

“This is important to rule out cases of PPID,” Macon said. “PPID could affect the results of the OST, so we want it to be clear that horses only have one metabolic disorder.”

They maintained the horses for the entire study period on pasture with additional hay as required, and they collected morphometric measurements and oral sugar test samples in February, April, August, and October.

The oral sugar test involves collecting baseline insulin and glucose samples (T0) after a grain-fast and then administering corn syrup orally at a body-weight determined dose. Macon and team collected additional blood samples 60 minutes later (T60) for glucose and insulin analysis.

Macon’s team found no significant difference in the insulin-dysregulated and normal horses’ body weights across seasons (the entire course of the study). But when looking at each season individually they noticed body condition and cresty neck scores were significantly higher in the affected horses than the normal horses. And when comparing measurements from season to season, they also differences for both ID and normal horses. All horses had lower body condition scores in April than in February, regardless of insulin status, and higher scores in August than in April. However, Macon said these changes were not always significant.

As would be expected, she said, basal (baseline) insulin levels were significantly higher in the insulin-dysregulated group than in the control group, regardless of season; these values made ID diagnosis clear. Interestingly, she said, season had no significant effect on these values in the control horses, but affected horses had significant variability in their insulin basal values from season to season. Their October insulin values were significantly lower than their February and April levels and below the value veterinarians typically use to diagnose ID.

The insulin-dysregulated and control groups’ T60 post-oral-sugar-test insulin values were significantly different, regardless of season, but control horses’ values were not significantly different across seasons, said Macon. The control horses all remained under the threshold for ID diagnosis. However, the insulin-dysregulated horses had insulin values more than 2.5 times higher than the threshold for diagnosis in February and April, dropping to just over 1.5 times the threshold in October. Therefore, she said, season had a significant effect on the ID horses’ levels in February, April, and October.

Pasture nonstructural carbohydrate content stayed relatively stable (below 10%) across season and was only significantly higher in October. Crude protein content was significantly higher in February and April (just under 30%) than in August and October (just under 20%).

“NSC has been directly correlated to stimulating insulin responses,” Macon said, and UK researchers recently showed that protein can also stimulate insulin responses. “Since these horses are consuming forage only throughout the year-long study, it is important to note what factors could stimulate insulin responses.”

Macon concluded that season affects basal insulin and insulin response to the oral sugar test in insulin-dysregulated horses but not in control (again, insulin-normal) horses. Another interesting finding from this study, she said, was that the insulin-dysregulated horses’ body condition and cresty neck scores did not reflect their basal insulin scores. Therefore, they do not appear to be driving factors behind insulin dysregulation development. Forage nutrients don’t appear to be driving factors, either, she said.

Macon is currently investigating other possible factors they could reliably test, including adipokines (proteins secreted by adipose tissue), the hormone melatonin, ACTH, and pro-inflammatory cytokines (proteins important in immune system cell signaling).

The study did have limitations, she said, namely that they only measured metabolic responses once per season and collected and analyzed forage only once per day at the same time each day (forage’s nutrient content fluctuates throughout the day). The study horses were obese insulin-dysregulated horses; it’s not clear whether the same findings would have occurred had they been leaner or had PPID, she said.

This research does clearly show that horses need to be diagnosed and monitored for insulin dysregulation, and veterinarians must remember that both basal and post-oral-sugar-test insulin responses vary across seasons in these horses, Macon said. Researchers might need to develop seasonal reference ranges like those that have been created for diagnosing PPID using ACTH, she said.