Journal of veterinary internal medicine2026; 40(4); aalag186; doi: 10.1093/jvimsj/aalag186

High molecular weight adiponectin as an adjunct biomarker for insulin dysregulation in equids.

de Laat, MA
·
Fitzgerald, DM
·
Li, FI
·
Sillence, MN
·
McGree, JM

Abstract: Total adiponectin concentration is associated with hyperinsulinemia and laminitis risk in ponies but the high molecular weight (HMW) multimer is a more sensitive indicator of metabolic disease in other species and could be a useful biomarker for insulin dysregulation (ID). Objective: To determine a cut-off value for using HMW adiponectin as an adjunct diagnostic tool for ID. Methods: Cohort of 127 privately and university-owned horses and ponies of various breeds with 55 classified as ID positive and 72 as ID negative. Methods: Cohort study. Baseline and postprandial blood samples from an in-feed oral glucose test (0.75 g/kg dextrose) were used to determine ID status. Insulin and HMW adiponectin concentrations were measured using validated immunoassays. High molecular weight adiponectin cut-off values were derived with receiver-operator characteristic curve analysis using a bootstrap method to maximize the sum of sensitivity and specificity. Results: Median [IQR] HMW adiponectin concentration was higher (P < .001) in ID negative animals (4.19 [2-6.5] μg/mL) compared to ID positive animals (1.79 [0.63-3.5] μg/mL), with a cut-off value (95% CI) of 2.1 (1.26, 3.15) μg/mL (area under the curve 0.71; sensitivity 0.62; and specificity 0.74). Horses had higher (P < .001) HMW adiponectin concentrations (4.38 [2.22-7.3] μg/mL) than ponies (1.84 [0.64-3.75] μg/mL). However, HMW adiponectin did not differ between horses with and without ID, and both horse subgroups had concentrations higher (P ≤ .002) than ponies with ID. Conclusions: Use of a single cut-off value for HMW adiponectin as an adjunct biomarker for ID for both horses and ponies is not accurate.

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Publication Date: 2026-08-26 PubMed ID: 42647818PubMed Central: PMC13513755DOI: 10.1093/jvimsj/aalag186Google Scholar: Lookup

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Summary

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Overview

This study investigates the use of high molecular weight (HMW) adiponectin as a biomarker to help diagnose insulin dysregulation (ID) in horses and ponies.
The research aims to establish a cut-off value for HMW adiponectin that can distinguish between ID-positive and ID-negative equids to improve diagnosis accuracy.

Background

Insulin dysregulation (ID) is a metabolic condition in horses and ponies characterized by abnormal insulin regulation, often linked to diseases like laminitis.
Adiponectin, a hormone produced by fat cells, circulates in multiple forms, with the high molecular weight (HMW) form being a more sensitive indicator of metabolic disease in other species.
Previous studies show that total adiponectin concentration associates with insulin levels and laminitis risk in ponies, but HMW adiponectin may be a better biomarker for insulin dysregulation.

Objectives

To determine whether HMW adiponectin concentrations can be used as a reliable adjunct diagnostic tool for insulin dysregulation in equids.
To establish a specific cut-off value of HMW adiponectin that can accurately categorize insulin dysregulation status in horses and ponies.

Methods

A cohort of 127 horses and ponies from private and university ownership were recruited, including various breeds.
Among them, 55 were classified as ID positive and 72 as ID negative based on insulin responses.
Animals underwent an oral glucose test where they consumed feed with 0.75 g/kg dextrose, followed by blood sampling.
Insulin and HMW adiponectin concentrations in blood samples were measured using validated immunoassays.
Receiver Operating Characteristic (ROC) curve analysis with bootstrapping was used to identify the cut-off value for HMW adiponectin that maximizes sensitivity and specificity for diagnosing ID.

Results

Median HMW adiponectin concentration was significantly higher in ID-negative animals (4.19 μg/mL) compared to ID-positive animals (1.79 μg/mL).
A derived cut-off value of 2.1 μg/mL (95% CI: 1.26 to 3.15 μg/mL) was found from ROC curve analysis, with an area under the curve (AUC) of 0.71.
Sensitivity (true positive rate) was 62%, and specificity (true negative rate) was 74% at this cut-off.
Horses overall had higher HMW adiponectin concentrations than ponies (median 4.38 vs. 1.84 μg/mL).
However, within the horse subgroup, HMW adiponectin did not significantly differ between ID-positive and ID-negative animals.
Pony ID-positive animals had significantly lower HMW adiponectin than both horse groups, regardless of their ID status.

Conclusions

HMW adiponectin shows promise as a biomarker for insulin dysregulation in equids but is influenced by species differences between horses and ponies.
A single cut-off value for HMW adiponectin is not sufficiently accurate for diagnosing ID across both horses and ponies.
Diagnostic accuracy could be improved by developing species-specific cut-off values or by using HMW adiponectin alongside other clinical metrics.
This research highlights the complexity of metabolic disease diagnosis in equids and the importance of tailored biomarkers for different subgroups.

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APA

de Laat MA, Fitzgerald DM, Li FI, Sillence MN, McGree JM. (2026). High molecular weight adiponectin as an adjunct biomarker for insulin dysregulation in equids. J Vet Intern Med, 40(4), aalag186. https://doi.org/10.1093/jvimsj/aalag186