Serum adipokines are useful for predicting hyperinsulinemia secondary to corticosteroid treatment in horses.

Overview

• This study investigated whether certain blood biomarkers, specifically serum adipokines, can predict the severity of hyperinsulinemia (high insulin levels) caused by corticosteroid treatment in healthy horses.

Background and Purpose

• Corticosteroids are commonly used medications in horses but can induce hyperinsulinemia, which may lead to serious complications like laminitis, a painful hoof condition.
• The ability to predict which horses are at risk of developing corticosteroid-induced hyperinsulinemia is important for prevention and safer clinical management.
• Adipokines, such as adiponectin and leptin, are hormone-like substances produced by fat tissue and are known to influence insulin metabolism in humans and animals.
• The study aimed to evaluate if pretreatment levels of these adipokines and their ratios, along with insulin and glucose levels, can predict the extent of hyperinsulinemia after corticosteroid administration.

Methods

• Subjects: 24 healthy adult Standardbred horses were enrolled.
• Treatment Protocol: Horses received a course of dexamethasone (a corticosteroid) at 0.08 mg/kg every 48 hours.
• Testing Timeline:
  • Day 1 (pretreatment): Oral glucose tests (OGTs) were conducted, and blood samples were taken to measure insulin, glucose, adiponectin, leptin, and ratios such as leptin-to-adiponectin.
  • Day 8 (post-treatment): OGTs were repeated to assess insulin response after corticosteroid treatment.
• Measured Insulin Parameters on Day 8:
  • Baseline insulin (T0insulin)
  • Maximum insulin concentration during the OGT (Cmaxinsulin)
  • Area under the insulin curve (AUCinsulin), representing total insulin exposure during the test
• Statistical Analysis:
  • Spearman correlation coefficients were used to examine associations between pretreatment biomarkers and post-treatment insulin measures.
  • Generalized linear models evaluated which pretreatment markers best predicted hyperinsulinemia.
  • Risk ratios were calculated to quantify the likelihood of exceeding clinically relevant insulin thresholds based on biomarker levels.

Key Results

• Insulin levels increased dramatically after corticosteroid treatment:
  • Baseline insulin (T0insulin) increased on average 11.5-fold, ranging 2 to 37 times higher than pretreatment levels.
  • Maximum insulin (Cmaxinsulin) rose on average 6.5-fold (range 2 to 17 times).
  • Insulin area under curve (AUCinsulin) increased approximately 6.6-fold (range 2 to 15 times).
• The strongest predictor was adiponectin measured before treatment:
  • Negative correlation with maximum insulin (Cmaxinsulin); higher adiponectin predicted lower hyperinsulinemia (correlation coefficient ρ = -0.67).
  • Negative correlation with insulin AUC (ρ = -0.68).
• The leptin-to-adiponectin ratio before treatment showed the strongest positive correlation with resting insulin after treatment (ρ = 0.68), indicating horses with higher ratios had higher baseline insulin post-treatment.
• Generalized linear model analysis confirmed that leptin-to-adiponectin ratio was the best overall predictor of all key insulin parameters (T0insulin, Cmaxinsulin, AUCinsulin).
• Horses with pretreatment leptin-to-adiponectin ratios above the normal reference range were nearly 5 times more likely to have clinically significant hyperinsulinemia (day 8 baseline insulin > 100 µIU/mL).

Conclusions and Clinical Implications

• Pretreatment measurement of adipokines, especially the leptin-to-adiponectin ratio, can effectively predict which horses are at increased risk for developing corticosteroid-induced hyperinsulinemia.
• Identifying at-risk horses before corticosteroid administration can aid veterinarians in making informed decisions about corticosteroid use, perhaps opting for alternative treatments or increased monitoring.
• Since corticosteroid-induced hyperinsulinemia is a risk factor for laminitis, adipokine biomarkers might also help predict laminitis risk and improve preventative care.
• The study suggests that clinical adoption of adipokine measurements could enhance the safety of corticosteroid therapy in horses.
• Further clinical evaluation and validation of adipokines as biomarkers in a broader equine population are warranted.