Metabolic Syndrome in the Pregnant Mare

Metabolic syndrome is a term drawing together a seemingly disparate set of clinical findings in human patients, these including insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and atherosclerosis. Obesity is a common but not consistent finding. The term has been subsequently applied to horses with obesity, insulin resistance, hyperinsulinemia, and dyslipidemia. A chronic pro-inflammatory condition is thought to exist in metabolic syndrome, the most important sequelae of the condition in the horse being laminitic. The effects on pregnancy in the mare have not been elucidated; however, in humans, gestational diabetes, abortion, and fetal compromise have been shown to result.

1. Introduction

The concept of metabolic syndrome in the horse, while relatively new, is widely researched and reviewed.¹  In other species, including humans, the profound effects of excessive adipose tissue have been well documented, and this obesity is considered a key component in development of the metabolic syndrome. Metabolic syndrome was introduced as a diagnostic category to identify human individuals at risk of developing type 2 diabetes and atherothrombotic cardiovascular disease.²  This term has come to be applied to equines with obesity, insulin resistance, and hyperinsulinemia.

Studies involving the metabolism of the pregnant mare have revealed that insulin resistance is in fact a normal occurrence in the healthy pregnant mare enabling redirection of maternal nutrients to the developing fetus. However, in mares with metabolic syndrome, any metabolic abnormalities and endocrinopathies existing before the pregnancy is established will probably be exacerbated.

2. What Is Going on in Metabolic Syndrome?

Insulin resistance was first proposed as a cause of glucose intolerance, elevated insulin levels, dyslipidemia, and hypertension in humans over 20 years ago.³ Metabolic syndrome has developed from this concept, being defined as a combination of cardiovascular risk factors including such diverse components as visceral adipose accumulation, insulin resistance, hyperinsulinemia, hypertension, chronic inflammation, microalbuminemia, and a prothrombotic disorder leading to endothelial cell dysfunction and atherosclerosis.⁴ Research has largely centered on human subjects due to the increasing occurrence of metabolic syndrome and the serious cardiovascular effects associated with this condition. In the horse, while sharing many of the same components, laminitis is the condition of primary concern due to its potentially lethal sequelae. Considerable debate exists regarding the etiology and pathogenesis of metabolic syndrome, as no single unifying mechanism has been elucidated.⁵ A complex interaction between genetics, hormonal status, and nutrition is most likely.

Adipose tissue is not simply a store of excess energy but is rather an organ of diverse functions that plays a pivotal role in development of metabolic syndrome.⁶ Adipokines, biologically active secretions of adipose tissue, may play a role in the pathogenesis of insulin resistance, as some have been shown to have effects on insulin sensitivity and signaling.⁷ Adiponectin has antidiabetic effects and may be a novel therapy in metabolic syndrome.⁸ In contrast, resistin and tumor necrosis factor-α increase as pregnancy progresses, which is in contrast to levels of adiponectin. These levels correlate with the state of reduced insulin sensitivity often developed in the latter stages of pregnancy.⁹

3. Presentation in the Equine

Body Score

In the horse, overall body adiposity may not be indicative of metabolic syndrome, as the nuchal ligament adipose depot has been shown to have unique biological behavior with a greater tendency to contribute to inflammatory mediator production than other fat stores.⁶ Therefore, visceral fat may not contribute to the pathogenesis of obesity-related disorders in the horse as it does in other species.

Laminitis

Insulin resistance is associated with obesity in horses, and this is considered to be a contributing factor to the onset of pasture-associated laminitis in horses with metabolic syndrome.^{10 –12} The feeding of high starch diets has also been associated with insulin resistance and hyperinsulinemia, thereby increasing the risk of laminitis.^13,14

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