Metabolic changes induced by oral glucose tests in horses and their diagnostic use

Abstract

Background: Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation. Objectives: Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response. Animals: Twelve Icelandic horses in various metabolic states. Methods: Horses were subjected to 3 oral glucose tests (OGT; 0.5 g/kg body weight glucose). Basal, 120 and 180 minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis tandem mass spectrometry metabolomic assay. Insulin concentrations were measured using an ELISA. Analysis was performed using linear models and partial least-squares regression. Results: The kynurenine : tryptophan ratio increased over time during the OGT (adjusted P-value = .001). A high insulin response was associated with lower arginine (adjusted P-value = .02) and carnitine (adjusted P-value = .03) concentrations. A predictive model using only baseline samples performed well with as few as 7 distinct metabolites (sensitivity, 86%; 95% confidence interval [CI], 81%-90%; specificity, 88%; 95% CI, 84%-92%). Conclusions and Clinical Importance: Our results suggest induction of low-grade inflammation during the OGT. Plasma arginine and carnitine concentrations were lower in horses with high insulin response and could constitute potential therapeutic targets. Development of screening tools to identify insulin-dysregulated horses using only baseline blood sample appears promising.

Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses

“…Ten of 12 horses returned their insulin concentration back to the baseline level at 240 minutes. AUC, area under the curve and methionine sulfoxide concentration,19,27 our findings further characterize the metabolic phenotype of insulin-dysregulated horses.…”

“…Ours is the first study to provide absolute plasma concentrations of the comprehensive sphingolipid metabolome, covering the various sphingolipid pathways, in horses with a characterized insulin response during OGT. Building on previous metabolomics studies showing that a higher insulin response in horses was significantly associated with a higher plasma glycerophospholipid concentration and lower plasma arginine, acylcarnitines, spermidine, trans‐4‐hydroxyproline and methionine sulfoxide concentration, 19,27 our findings further characterize the metabolic phenotype of insulin‐dysregulated horses.…”

“…The acute challenge of OGT may not have a clinically relevant impact on sphingolipid metabolism, a finding that is in agreement with the results of a previous metabolomics study conducted using a PO sugar test in Welsh Ponies 28 that found that palmitoyl SM concentration did not differ statistically between 0 and 75 minutes of the PO sugar test. Furthermore, another study 19 showed that none of the 15 investigated species of sphingolipid were significantly changed after an acute OGT in horses. These studies collectively confirm the limited impact of an acute sugar load on sphingolipid metabolism in horses.…”

“…However, the impact of an acute OGT challenge on sphingolipid metabolism in horses has been characterized only for a limited number of sphingolipids, mainly SM. 19 , 20 , 21 The correlation between sphingolipids and insulin response has not yet been well established. We hypothesized that the OGT would alter plasma sphingolipid profiles, specifically that the acute activation of the insulin signaling pathway by an OGT would downregulate ceramide biosynthesis.…”

“…If this insulin resistance is caused by increased ceramide concentrations, it could explain the link between alteration in sphingolipid metabolism and ID. However, the impact of an acute OGT challenge on sphingolipid metabolism in horses has been characterized only for a limited number of sphingolipids, mainly SM 19‐21 . The correlation between sphingolipids and insulin response has not yet been well established.…”