South African Equine Veterinary Association Congress 2015 Protea Hotel Stellenbosch
Figure 1. Causes of laminitis reported in the
2000 USDA NAHMS study; note that grazing
lush pasture was the most common reported
cause with a peak incidence in May.
Pathophysiology: The cause of obesity is fairly straightforward: caloric intake exceeding daily
caloric expenditure. Clearly, there is also a genetic predisposition towards development of obesity
that has been referred to as having “thrifty genes”. Unfortunately, obesity has a number of
metabolic consequences including insulin resistance (IR), hyperglycaemia, altered tissue-level
cortisol activity, increased leptin concentrations, altered lipid metabolism with
hypertriglyceridemia, increased expression of inflammatory cytokines, and hypertension. In
horses, the most obvious clinical sign that results from these metabolic alterations is laminitis.
EMS appears to have some parallels to the human metabolic syndrome - a syndrome of IR and
visceral adiposity (deposition of omental fat) that is recognized to affect an increasing number of
middle-aged people. In affected humans, cardiovascular disease, hypertension, dyslipidemias, and
type II diabetes (insulin resistant diabetes) are the common sequelae.
The pathophysiology of laminitis in EMS-affected equids remains less clear. Development of
clinical laminitis in association with grazing lush pasture initially led to comparison with grain
overload (and models of carbohydrate overload to induce laminitis). In these scenarios, altered
hindgut fermentation and disruption of microbial flora and the mucosal barrier, leadi ng to
absorption of bacterial toxins and vasoactive amines, is thought to precipitate development of
laminitis by mechanisms that remain incompletely understood. Recent experimental studies in
ponies and Standardbred horses, however, found that laminitis could be induced within 48 hours
of starting intravenous infusions of insulin and glucose (hyperinsulinemic-euglycemic clamp
model). Because this model produces minimal disruption of the hindgut, these findings have
called into question the importance of hindgut changes in development of laminitis in EMS
horses. Rather, IR and accompanying metabolic changes induced by obesity are now considered
the most important factors in development of laminitis.
Incubation of hoof capsule explants in solutions without glucose results in rapid laminar
separation while the laminar attachment remains strong when glucose is added to the incubation
solution. Consequently, glucose starvation was an early hypothesis for development of laminitis
with IR, as lamellar tissue IR would limit glucose uptake. However, it was subsequently
discovered that lamina lack the glucose transporter (GLUT-4) that is regulated by insulin. Rather,
glucose enters lamellar cells via GLUT-1, a glucose channel that facilitates glucose transport
down a concentration gradient (from blood to the intracellular space) that is independent of
insulin‟s action. Because blood glucose concentration may be increased in some horses with IR,
and is clearly increased in diabetic patients, a subsequent hypothesis was that laminitis may be a
consequence of glucose toxicity to the laminar tissues. This was an attractive hypothesis because
glucose toxicity is a recognized pathogenic mechanism in diabetic patients, leading to vascular
changes that result in damage to the eyes and kidneys. However, horses with IR and persistent
hyperglycaemia (type II diabetes mellitus) do not appear to develop similar vascular damage in
51