The prospects of developing a screening tool to identify horses with insulin problems using only a baseline blood sample have been buoyed by the findings of recent research in Germany.
Equine metabolic syndrome encompasses a range of disorders of energy metabolism. Problems with insulin regulation are a hallmark of the syndrome, as is obesity. The syndrome places horses at high risk of developing laminitis.
The oral glucose test involves the administration of a fixed amount of glucose through a nasogastric tube. By measuring the resulting insulin concentrations in blood, the insulin response can be quantified, providing a diagnostic tool for the identification of hyperinsulinemia and prediction of laminitis risk.
The metabolic mechanisms triggered by carbohydrate intake during the oral glucose test are of interest because they might reflect what happens when hyperinsulinemic horses are grazing, Julien Delarocque and his colleagues noted in the Journal of Veterinary Internal Medicine.
The research team, with the University of Veterinary Medicine Hannover, noted that many studies had been undertaken in a bid to identify markers of the inflammatory processes associated with hyperinsulinemia, laminitis, or obesity in horses.
The identification of long-sought biomarkers of hyperinsulinemia useful for diagnostic screening in baseline blood samples would limit the need for oral glucose challenges and other complex tests, they said.
Their study involved 12 Icelandic horses in various metabolic states. They were subjected to three oral glucose tests over seven weeks, receiving 0.5 grams of glucose per kilogram of body weight.
Blood samples were taken before, then 120 and 180 minutes after the administration of the glucose.
Analysis work was undertaken to better understand the response of the horses to the glucose test at a metabolomic level. Metabolomics is the study of chemical processes involving metabolites.
The study team reported that results from previous experiments in horses had been confirmed, but several new potential biomarkers for hyperinsulinemia were also identified.
They found that the ratio of kynurenine: tryptophan, both amino acids, increased over time during the glucose test, pointing to a low‐grade inflammatory response from the glucose challenge.
A high insulin response was associated with lower concentrations of arginine and carnitine, both metabolites linked to beta‐oxidation.
“Oral supplementation of carnitine and arginine have already been used successfully against metabolic disorders in several species and could be investigated as potential therapeutic targets,” they said.
Of the 14 amino acids that varied significantly over time, only tryptophan and glycine had a positive concentration gradient during the test, whereas all others were negative.
“In our study, the effect of artificial hyperinsulinemia was investigated in a hypothesis‐driven metabolomics approach. It remains to be confirmed if naturally occurring hyperinsulinemia has a similar metabolic impact.
Several metabolites involved in inflammatory processes and vascular dysfunction, potentially involved in the progression of insulin dysregulation or laminitis, were identified. However, because laminitis was not induced during the study, additional experiments on larger groups of horses were warranted.
The complexity and costs of metabolomics analysis meant it was not feasible to use large metabolite panels for diagnostic purposes in animals. So, could similar accuracy be achievable using fewer metabolites?
A predictive model using only baseline samples performed well with as few as seven distinct metabolites — a feasible number to include in a point‐of‐care device.
They concluded: “Although confirmatory studies still are required, our results may aid in development of a point‐of‐care device to identify hyperinsulinemic horses using a single unstimulated blood sample.”
The study team comprised Delarocque, Florian Frers, Karsten Feige, Klaus Jung, and Tobias Warnken, all with the University of Veterinary Medicine Hannover; and Korinna Huber, with the University of Hohenheim in Stuttgart.
Metabolic changes induced by oral glucose tests in horses and their diagnostic use
Julien Delarocque, Florian Frers, Karsten Feige, Korinna Huber, Klaus Jung, Tobias Warnken.
Journal of Veterinary Internal Medicine, 05 December 2020, https://doi.org/10.1111/jvim.15992