Survival of species evolving in nutritionally sparse environments, including hunter-gatherer humans and rugged pony breeds, was probably facilitated by thrifty genes and insulin resistance.1 Since the agricultural revolution, grains and improved pastures have supplied abundant soluble carbohydrates to humans and horses. High carbohydrate diets exacerbate insulin resistance,2,3 transforming the evolutionary advantage of insulin resistance to a predisposition for certain diseases, notably type 2 diabetes mellitus4 and coronary heart disease5 in humans and—so far somewhat speculatively—laminitis in equids.6,7
Pasture-associated laminitis accounts for 54% of cases of equine laminitis for which the initial cause is identifiable. Other initial causes include grain overload (8%) and miscellaneous feeding problems; diarrhea and colic; and complications of injury, obesity, and pregnancy (each < 5%).8
Most research associated with laminitis in horses has used experimental models yielding results that pertain mainly to pathogenic events in the acute stage, when separation of the hoof wall from the pedal bone is beginning.9,10 Once separation occurs, there is little opportunity for effective intervention.11
Preceding the acute stage of laminitis is a prodromal or developmental stage of many hours during which trigger factors, possibly including exotoxins, endotoxins, amines, or inflammatory cytokines, are circulating and presumably causing latent vasoactive, structural, and metabolic abnormalities.9 By this stage, effective intervention may not be possible. Intervention to avoid the release of triggers may prove more efficacious. In the opinion of the authors, however, the most likely opportunities for intervention reside in identifying predisposing conditions in ponies and avoiding environmental, mainly nutritional risk factors to preempt the disease.
In humans, 2 metabolic syndromes have been defined that predict an increased risk of disease. One pertains to type 2 diabetes mellitus, with a diagnostic definition requiring insulin resistance or glucose intolerance, and any 2 of high triglycerides or high density lipoprotein-cholesterol concentrations, hypertension, or microalbuminemia.4 The other pertains to coronary heart disease, with a diagnostic definition including any 3 of high glucose, triglycerides, or high density lipoprotein-cholesterol concentrations; hypertension; or abdominal obesity.5 Extensive scientific evidence has been collected to identify these risk factors and define quantitative cutoff values to characterize each predisposition. Because these metabolic syndromes are predictive, they are meaningful only in the diagnosis of apparently healthy individuals.12
An equine metabolic syndrome has been proposed as a form of mild to moderate laminitis characterized by consistent fasting hyperinsulinemia and hyperglycemia and obesity in most, but not all, cases.7 The existence of this syndrome has not been substantiated by published data that differentiate horses characterized with equine metabolic syndrome from other horses with mild to moderate laminitis or from healthy horses.13 In contrast, the study reported here derives a prelaminitic metabolic syndrome from substantial observations on apparently healthy ponies.
The original World Health Organization definition of a prediabetic metabolic syndrome stipulated the use of the euglycemic-hyperinsulinemic clamp to assess insulin resistance.4 Specific quantitative methods for assessing insulin resistance, such as the clamp and the minimal model, are more precise than 1-sample proxy tests; however, they are technically complex and expensive. Proxies or surrogates have been developed for screening purposes and have been advocated in studies of metabolic syndrome in humans.14,15
In humans, the concept of a metabolic syndrome as a set of risk factors was advanced originally as syndrome X,16 the expression of a genetic predisposition, which was exacerbated by a high carbohydrate diet. Results of pedigree analysis of families of 22 affected children have since suggested that metabolic syndrome in humans is inherited as an autosomal dominant trait.17
The purpose of the study reported here was to evaluate genetic and metabolic predispositions and nutritional risk factors for development of pastureassociated laminitis in ponies.
Reciprocal of the square root of insulin
Modified insulin-to-glucose ratio
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