Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with equine Cushing's disease

Abstract

Summary Reasons for performing study: The mechanisms underlying the increased risk of laminitis in horses with equine Cushing's disease (ECD) are poorly understood. Hypothesis: That abnormalities in glucose homeostasis, similar to those which cause microvascular dysfunction in human diabetics, contribute to development of laminitis in horses with ECD. Methods: Thirty‐one aged horses were divided into 3 groups based on clinical signs and dexamethasone suppression testing (DST). Group 1 (n = 12) had clinical ECD as evidenced by hirsutism. Group 2 (n = 10) had a positive DST but no hirsutism. Group 3 (n = 9) were controls without ECD, with a negative DST and no clinical evidence of ECD. Biochemical indices of glucose metabolism, vascular function and oxidative stress were determined in single morning blood samples. Results: Group 1 had abnormalities in glucose homeostasis, including increased levels of glucose and insulin, compared to Groups 2 and 3. Groups 1 and 2 had significantly lower plasma thiol (PSH) levels and nonsignificantly lower albumin‐corrected PSH levels than Group 3, consistent with oxidative stress. Conclusions and potential relevance: The observed abnormalities in glucose metabolism and oxidative stress could potentially contribute to development of laminitis in horses with ECD, by similar mechanisms to those that cause microvascular dysfunction in human diabetics. The absence of inter‐group differences in the biochemical indices of vascular function precludes their use as preclinical diagnostic indicators of vascular dysfunction. The study also highlighted limitations in the premortem diagnosis of ECD.

Reference Point: Exploring fructosamine beyond diabetes mellitus

“…Long-term therapeutic dosages of methylprednisolone and triamcinolone in atopic cats resulted in a total mean increase in fructosamine concentration of 49.1 µmol/L, although albumin concentrations also significantly increased in both treatment groups. 15 Sex-When matched on the basis of weight, body condition score, and age, male cats were shown to have significantly higher fructosamine concentrations versus females (279.9 ± 42.6 µmol/L and 249.0 ± 36.0 µmol/L, respectively), with no significant differences in total protein concentration between male and female cats. Although fructosamine concentration increased significantly over time in both treatment groups, the magnitude of this increase was greater in the dexamethasone-treated cats, compared with those treated with prednisolone.…”

“…Fructosamine acts as a reducing agent for NBT under alkaline conditions, resulting in the generation of formazane at a rate directly proportional to fructosamine concentration. To date, the modified NBT assay has been validated for use in numerous species, including dogs, 54 cats, 55 ponies, 8 horses, 15 and cattle. A pH between 10.5 and 11 is often used to limit interference by free glucose, which also reduces NBT at alkalinities outside of this range.…”

“…1 Formation of fructosamine is proportional to the degree and duration of hyperglycemia within the patient. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] It has also been shown to be a useful marker for differentiating nondiabetic causes of glucosuria. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] It has also been shown to be a useful marker for differentiating nondiabetic causes of glucosuria.…”

Therapeutic Plasma Concentrations of Epsilon Aminocaproic Acid and Tranexamic Acid in Horses

“…Therapeutic plasma concentrations of EACA and TEA have not been determined in horses, and current dosing recommendations for EACA (3.5 mg/kg/min for 15 minutes followed by 0.25 mg/kg/min for the treatment period) target therapeutic plasma concentrations established in humans . However, there is evidence that healthy horses may have decreased fibrinolytic activity compared to people, as indicated by lower basal plasminogen activity and increased α‐2 antiplasmin and plasminogen activator inhibitor‐1 (PAI‐1) activity in adult horses and foals . In addition, horses require 10‐fold higher concentrations of tissue plasminogen activator (tPA) to induce fibrinolysis in an in vitro assay compared to humans .…”

Evaluation of antioxidant systems in pituitary-adrenal axis diseases

“…Relative incompetence of blood alphatocopherol (with absence of increasing age-related levels as in normal subjects) accompanied by its decreased levels in the red blood cells was described [22]. Finally, a significant lowering in plasma thiol levels (even when corrected for albumin), consistent with oxidative stress, were shown in animal models (equine Cushing's disease) [23].…”