Evaluating insulindysregulation in horses: A two-step insulin-tolerance test using porcine zinc insulin.

In insulin dysregulation, hyperinsulinemia (HI) can be accompanied by peripheral insulin resistance (IR) in horses, which can be diagnosed with an insulin-tolerance test (ITT). The administration of 0.1 IU/kg body weight of recombinant regular human insulin (RHI) should elicit a 50 % reduction of the initial blood glucose concentration at 30 min after insulin administration in insulin sensitive horses. Compared to RHI, porcine zinc insulin (PZI) is veterinary-approved and therefore easier accessible for many practitioners. The aim of this study was to compare the insulin and glucose dynamics during a standard ITT with RHI to an ITT performed with PZI. Twelve Icelandic horses were subjected to an ITT with RHI (ITT-RHI) and with PZI (ITT-PZI) at same dosages in a randomised crossover design. The insulin and glucose dynamics that resulted from these tests were compared, and the consistency of classification into insulin-sensitive and IR categories was evaluated. No complications were observed with the use of either RHI or PZI in ITT. A good correlation of the test results was observed (r = 0.88; P < 0.001). The blood glucose concentrations and the percentage reduction in glucose concentration did not differ significantly between the two tests (P = 0.053), but four out of twelve horses were classified as IR in the ITT-RHI whereas with the ITT-PZI seven out of twelve horses were classified as IR with the 50 % glucose reduction from baseline. Based on the Youden index, when using the ITT-PZI, an adjusted cut-off value for blood glucose reduction of 40 % at 30 min resulted in better test performance. With consideration for the seemingly weaker effect of PZI and the adjusted cut-off value, PZI can be an appropriate substitute to RHI in an ITT.

Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses.

Both, oral and intravenous (IV) testing protocols, are recommended and still used to detect insulin dysregulation (ID) in equids. However, IV tests mainly focus on peripheral insulin resistance (IR), while oral tests assess hyperinsulinemia (HI), which are different aspects of ID. The objective of this study was to describe if horses with HI also demonstrate IR and consequently can be detected by a modified 2-step insulin response test (2-step IRT) performed with a veterinary approved porcine zinc insulin (PZI). Twelve Icelandic horses were subjected to an OGT and 2-step IRT in a crossover study. Serum insulin concentrations during the OGT revealed that six horses were hyperinsulinemic (HI) while six were not (NON-HI). To describe the glucose response to IV injected PZI, the decline of plasma glucose concentration within the first 30 min was analyzed. Glucose reduction was similar in horses with and without HI during the 2-step IRT over time. Additionally, none of the horses reached a glucose reduction of ≥ 50% at 30 min. The results of the present study indicated that a comparable insulin mediated glucose uptake may be observed in horses with and without HI during a modified 2-step IRT. While six out of twelve horses were identified as HI by the OGT, all twelve horses were identified as IR by the modified 2-step IRT performed with PZI underlining the importance, but difficulty in choosing the right diagnostic tool in clinical settings to assess ID.

Effect of fentanyl on thermal and mechanical nociceptive thresholds in horses and estimation of anti-nociceptive plasma concentration.

There are few investigations relating anti-nociception to plasma concentrations of fentanyl in horses. The study objective was to evaluate analgesic efficacy and duration in horses and determine the minimum anti-nociceptive plasma concentrations. Eight horses were treated with saline (P) and fentanyl (F2.5=2.5µg/kg; F5=5µg/kg; F10=10µg/kg) given IV over 5min, with a wash-out period of 10 days. To evaluate thermal (°C) and mechanical (N) nociceptive threshold single stimulations were applied prior to (baseline) and 10, 30, 60, 90, 120, 180, 240, 300, 360, 420, 540min and 22.5h after treatment. Plasma fentanyl concentrations were measured at specific time points. Locomotor activity, heart rate, respiratory rate and gastrointestinal sounds were recorded. Two-way repeated measures ANOVA and pairwise comparisons were used for data analysis (P<0.05). With treatment F10, there was a significant increase in thermal threshold above baseline (47.2ö4.1°C) at t10 (53.7ö4.2°C) and t30 (52.1ö5.6°C), whereas mechanical threshold increased considerably above baseline (3.7ö1.3N) only at t10 (6.6ö3.6N). Estimated mean minimum anti-nociceptive plasma concentration determined by thermal stimulation was 6.1-6.8ng/mL. Dose-dependent increased locomotion occurred, but no significant changes in heart rate, respiratory rate and gastrointestinal sounds were observed. Fentanyl IV at 10µg/kg produced anti-nociception for 10-30min and fentanyl plasma concentrations of ≥6.1-6.8ng/mL appear necessary to induce thermal anti-nociception. Dose-dependent increased locomotion was the main side effect observed.