Original Research
Characterization of Glucose Response Curves after Insulin Injection in Sensitive versus Insensitive Mares

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Abstract

The glucose responses to intravenous injections of a range of doses of recombinant human insulin were determined for six mares known to be insulin sensitive and six mares known to be insulin insensitive, with the goal of better characterizing the regression lines resulting from the two categories of mares. Insulin doses between 8 and 198 mU of insulin per kg of body weight (mU/kg BW) were administered intravenously between September 13 and 26, 2010, starting with 50 mU/kg BW on the first day. Higher and lower doses were administered on alternate days to obtain percentages of decreases in blood glucose concentrations between 10% and 70%. Linear regression analysis revealed that insulin-insensitive mares have glucose response curves with higher y intercepts (P = .066), less steep slopes (P = .0003), and less goodness of fit (P = .053) in addition to the expected greater dose required to produce a 50% reduction in blood glucose concentrations (ED50; P = .006), despite the similarities between their body weights and those of insulin-sensitive mares. Linear and nonlinear regression of responses to the 32, 50, and 79 mU/kg BW insulin doses with the overall estimates of ED50 and the natural log of ED50 indicated that the 50 mU/kg BW dose had the greatest coefficient of determination (>0.95). Generally, it appears that estimates of insulin sensitivity based on a single injection of insulin or on multiple injections of insulin are least variable for insulin-sensitive mares.

Introduction

Caltabilota et al. [1] reported that the percentage of decrease in serum glucose concentrations in mares after injection of recombinant human insulin could be used to determine insulin sensitivity, with the limitation that multiple data points, preferably three, be obtained between decreases of 10% and 70%, at which point the dose-response curve is linear. Subsequently, Bertin and Sojka-Kritchevsky [2] reported a two-step method based on a single dose of insulin, which compared favorably with the protocol of Caltabilota et al. [1].

In the development of the original technique, Caltabilota et al. [1] noticed that mares with low insulin sensitivities seemed to have less steep dose-response curves. That is, the incremental percentage of decrease in glucose concentrations with each higher dose of insulin in insulin-insensitive mares was not as much as that for insulin-sensitive mares. Caltabilota et al. [1] suggested that three doses of insulin produced the most reliable estimates of insulin sensitivity, even though the response to a single dose of 50 mU per kg of body weight (mU/kg BW) did in fact provide a close approximation to the final sensitivity estimate in most insulin-sensitive mares but less so in mares later diagnosed with insensitivity.

The present experiment was conducted to better characterize the insulin-glucose dose-response curves in mares (a minimum of 5 points) so that differences among horses of differing sensitivities could be assessed. Data from these curves were subsequently used to estimate the predictability of single-injection results compared to those obtained with the multipoint curves.

Section snippets

Materials and Methods

All procedures described herein were approved by the Institutional Animal Care and Use Committee of the Louisiana State University Agricultural Center. Twelve mares, six known to be insulin insensitive and six known to be insulin sensitive (determined multiple times over several years), were used in this experiment. The mares were between 6 and 16 years of age, weighed between 450 and 650 kg, and had body condition scores of 6 or greater [3]. They were routinely housed on native grass pasture

Results

The pooled regression lines of the log natural doses of insulin plotted versus the percentage decrease in glucose concentrations for the individual mares in the sensitive and insensitive groups in this experiment are shown in Figure 1. Analysis of those regression data revealed that mares considered insulin insensitive in previous trials had a higher y intercept (−35.45% vs. −52.6%; P = .066) (Fig. 2). These insensitive mares also displayed a less steep slope (15.4% vs. 26.2% increase per ln

Discussion

Caltabilota et al. [1] were the first to formalize the use of insulin injection to directly estimate insulin sensitivity in horses. Bertin and Sojka-Kritchevsky [2] subsequently modified their protocol into a two-step method for on-farm use. The previous applications of the hyperinsulinemic-euglycemic clamp [5], [6] and the minimal modeling of the frequently sampled intravenous glucose tolerance test [7], [8] were considered the currently acceptable methods for estimating insulin sensitivity in

Acknowledgments

This report was approved for publication by the director of the Louisiana Agricultural Experiment Station as manuscript number 2012-230-7781.

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