Evaluation of fasting plasma insulin and proxy measurements to assess insulin sensitivity in horses

Abstract

Background Proxies are mathematical calculations based on fasting glucose and/or insulin concentrations developed to allow prediction of insulin sensitivity (IS) and β-cell response. These proxies have not been evaluated in horses with insulin dysregulation. The first objective of this study was to evaluate how fasting insulin (FI) and proxies for IS (1/Insulin, reciprocal of the square root of insulin (RISQI) and the quantitative insulin sensitivity check index (QUICKI)) and β-cell response (the modified insulin-to-glucose ratio (MIRG) and the homeostatic model assessment of β-cell function (HOMA-β)) were correlated to measures of IS (M index) using the euglycemic hyperinsulinemic clamp (EHC) in horses with insulin resistance (IR) and normal IS. A second objective was to evaluate the repeatability of FI and proxies in horses based on sampling on consecutive days. The last objective was to investigate the most appropriate cut-off value for the proxies and FI. Results Thirty-four horses were categorized as IR and 26 as IS based on the M index. The proxies and FI had coefficients of variation (CVs) ≤ 25.3 % and very good reliability (intraclass correlation coefficients ≥ 0.89). All proxies and FI were good predictors of the M index (r = 0.76–0.85; P < 0.001). The proxies for IS had a positive linear relationship with the M index whereas proxies for β-cell response and FI had an inverse relationship with the M index. Cut-off values to distinguish horses with IR from horses with normal IS based on the M index were established for all proxies and FI using receiver operating characteristic curves, with sensitivity between 79 % and 91 % and specificity between 85 % and 96 %. The cut-off values to predict IR were < 0.32 (RISQI), < 0.33 (QUICKI) and > 9.5 µIU/mL for FI. Conclusions All proxies and FI provided repeatable estimates of horses’ IS. However, there is no advantage of using proxies instead of FI to estimate IR in the horse. Due to the heteroscedasticity of the data, proxies and FI in general are more suitable for epidemiological studies and larger clinical studies than as a diagnostic tool for measurement of IR in individual horses.

Development of a Web App to Convert Blood Insulin Concentrations among Various Immunoassays Used in Horses

“…Firstly, the outcome used to establish the cut-off must be considered. Some studies relied on diagnostic tests, such as the euglycemic hyperinsulinaemic clamp (EHC) [35] or combined glucose-insulin test (CGIT) [36], to detect insulin-resistant horses, while others were conducted prospectively, with laminitis as an outcome [37][38][39]. Another study reported a confidence interval for basal insulin in healthy ponies [41].…”

“…Despite all these differences, the published cut-offs for basal insulin values with laminitis as an outcome averaged at around 30 µIU/mL once converted to the Mercodia Equine assay [37][38][39]. The cut-offs targeting insulin resistance or ID were lower at around 10 to 20 µIU/mL (once converted) [34][35][36]41]. This is unsurprising, as the likelihood of laminitis incidence is correlated with the degree of hyperinsulinaemia, meaning that slightly insulin-resistant horses may not develop laminitis at all, even though they remain at risk.…”