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Insulin resistance (IR) is defined as reduced sensitivity to insulin that results in increased insulin release and/or decreased activity of insulin, such as glucose entry into cells, inhibition of glucose production in the liver, and mobilization of fat. Laboratory testing for IR in horses reveals elevated blood insulin concentration or abnormal changes in blood insulin and/or glucose concentrations when the horse is challenged with glucose or insulin. Several tests have been developed to investigate IR, but most involve either oral or intravenous glucose administration, and in some tests, insulin is also administered.

Insulin resistance can be caused by several hormones and drugs that affect the actions or release of insulin. These are listed below.

Gestational diabetes occurs during pregnancy when progesterone inhibits insulin. This is not common in mares but occurs in other species.

Xylazine and detomidine, two commonly administered equine sedatives, inhibit the release of insulin from the pancreas. In adult horses, these drugs quickly lower blood insulin and can raise blood glucose concentrations for over three hours.

Stress or severe illnesses induce the release of hormones that interfere with insulin, such as cortisol and epinephrine. It is not unusual for stressed or ill horses to have elevated blood glucose concentrations, though these usually return to normal as the animal relaxes or its condition improves.

Pituitary pars intermedia dysfunction (equine Cushing’s disease)occurs in older horses due to dysfunction of the pituitary gland that results in the overproduction of cortisol, which antagonizes insulin.

Equine metabolic syndrome(EMS) is similar to type II diabetes mellitus in humans. Type II diabetes usually affects obese adults and is characterized by elevated blood glucose concentration resulting from impaired insulin utilization and an inability to compensate with increased insulin production. Equine metabolic syndrome usually occurs in overweight younger horses that have abnormal fat deposits. Affected horses are often described as easy keepers that maintain or gain weight despite being fed relatively small amounts. Insulin resistance with EMS is theorized to occur because abnormal fat can secrete hormones (cytokines and adipokines) that down-regulate pathways involved with how insulin acts on cells. The accumulation of fat in tissues such as skeletal muscle is also believed to have some toxic effects on cells and their response to insulin (lipotoxicity). Fat can convert inactive cortisone to its active form cortisol, which can further add to IR. It is important to realize that not all overweight or obese horses are affected with EMS or IR.

Glycemic index is the measure of the rate of rise in blood glucose concentration in response to eating a specific feedstuff. Glycemic index depends on the carbohydrate content of the feed. In general, feeds with a higher amount of starch, nonstructural carbohydrates, or other sugars will have a higher glycemic index than feeds high in fats or fermentable fiber. Glycemic index evaluates how blood glucose changes when a horse is fed a given feedstuff and should not be confused with IR. However, if IR is present, it will decrease the clearance of glucose from the blood because the normal actions of insulin (drive glucose into cells and thereby decrease blood insulin concentration) are inhibited. Blood glucose concentrations will fluctuate less when a horse is fed a feed with a low glycemic index. In other species, high-fat diets can actually worsen IR; however, this effect has not been extensively investigated in horses.

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