| Chronic or recurrent laminitis is believed by some
researchers to have a basis in insulin resistance, which causes decreased
blood glucose to the foot's tissues. These histologic changes closely mimic
those seen in peripheral neuropathies in human diabetics. If additional
research confirms these theories, then new and potentially powerful methods
of treating equine laminitis by way of addressing glucose homeostasis may be
forthcoming. Seven of your clients' horses are being fed the same grain
diet, being pastured on the same grass field and being exercised the same
way. Yet only one of them experiences an episode of laminitis. Why?
You have treated the last 10 cases of laminitis presented to your clinic
with good aggressive management and cutting-edge treatment and while most
have responded and done well, a few have been slow to respond. Perhaps one
or two, despite doing everything you could do, did not improve and were
ultimately lost. Why?
There are some horses in your practice that are such easy keepers that
they seem to get fat on air. They have thick, cresty necks and fat deposits
over their backs and hips, though the owners have them on minimal rations.
Your clients report that these horses have tremendous appetites though they
are obviously fat. Dietary management is less than rewarding and exercise
does not work well, as these horses seem to be slow and lethargic with poor
muscle development. Why?
There is an 8-year-old horse in your practice exhibiting clinical signs
that you have seen before. He is overweight and may have excess fatty
deposits through his back or crest. He has a long, coarse haircoat that may
not shed well and he may have problems sweating normally. This horse may
have recurrent laminitic problems or may be prone to dermatitis or other
infections. You think that this horse has Cushing's disease but he is too
young and the blood work does not support that familiar diagnosis. Why?
Common cause
The answer to these questions may lie in a relatively common disease of
humans but one that has been rare, at best, in horses. Typically diabetes
has been thought to be uncommon in horses.
A literature review of the last 50 years shows a small number of cases of
equine diabetes that were caused by either pancreatitis or by tumors of the
pituitary gland.
Recently, however, researchers have speculated that horses may be much
more inclined to develop a resistance to insulin that can lead, as in
humans, to adult-onset or type-2 diabetes. These horses may mimic Cushinoid
horses without the appropriate blood test results and they may exhibit a
variety of clinical signs and disease patterns that have been confusing
veterinarians for some time. Perhaps it is because horses are living longer
and we are now seeing more and more of these cases. Perhaps these cases were
always there but were going undiagnosed.
Increased care and attention are more commonly being paid to equine
senior citizens and problems that might have been overlooked as simply
"complications due to aging" are now being closely investigated. Any number
of factors may have made diabetes more of a potentially recognizable disease
in horses but the impact of this diagnosis is important.
Because this theory of insulin resistance and eventual diabetes answers a
number of existing questions and because it fills in the holes in our
understanding of a number of disease processes, it is being referred to as
the "unification theory." If additional research confirms these
speculations, this theory may point to some exciting new treatments for some
old, frustrating problems.
No response
Insulin resistance is a condition that develops when the body's cells do
not correctly respond to insulin.
Insulin secretion from the pancreas is triggered by a rise in blood
glucose after eating a meal containing sugars or starches. Insulin
stimulates cells to take up this circulating glucose and once in the cell it
is used for energy or converted to glycogen or fat for storage. In
conditions of insulin resistance, the cells do not respond to normal levels
of insulin.
At first the body simply produces more insulin and these higher levels
regulate blood glucose. Gradually though, the body fails to respond to
higher and higher levels of insulin and eventual exhaustion and failure of
the insulin producing cells of the pancreas occurs. At this point, type 2
diabetes is said to exist. The "unification theory" would encourage
veterinarians to look more closely at individual cases and not to put all
older, hairy, overweight horses into the "Cushing's disease" category. Some
of these horses may be insulin resistant and may respond to different
treatment protocols.
The exact dividing line is not specific. In fact, in humans there is a
level of damage prior to diabetes that is called impaired glucose tolerance
(IGT). These levels or conditions are partially academic and the bottom line
is that insulin resistance should be looked at as a precursor to more
serious disease and treated accordingly.
Resistance
Typically, insulin resistance is associated with obesity because of the
metabolic changes the body goes through as the blood glucose levels rise.
Temporary insulin resistance has been noted to occur in conditions of
inflammation, infection, injury and other conditions involving hormonal
variations such as puberty and pregnancy. It is not exactly known how
insulin resistance relates to these disease states but human studies have
shown that sustained elevated blood glucose leads to changes in the
microvasculature of many tissues and the production of various cellular
cytokines. These particles, in turn, cause reduced nerve perfusion and
eventual hypoxia and tissue death.
It is well established that humans suffering from diabetes are at risk of
developing severe infections, kidney and liver damage and peripheral nerve
and vessel damage often leading to loss of digits or toes. Foot disease is,
in fact, the most common complication of diabetes leading to
hospitalization.
Of greatest benefit
It is here, in the discussion of foot disease, that the unification
theory may benefit horses the most.
Recent research by Dr. C.C. Pollitt of the School of Veterinary Science
at the University of Queensland in Australia suggests an underlying cause of
all laminitis cases may be altered glucose metabolism. Lack of glucose in
peripheral tissue of humans (as seen with diabetes) leads to peripheral
neuropathy and to ischemic damage.
In Pollitt's studies, impaired glucose in hoof extract tissue led to
damage of the basement membrane and separation of the dermal laminae from
the epidermal laminae. This explains why one specific horse (that may be
insulin-resistant to some degree) would founder when others in a similar
environment do not or why one horse may not respond to laminitis treatment
while other affected horses do respond.
Insulin resistance could be secondary to elevated cortisol levels
resulting from primary Cushing's disease or from exogenous corticosteroid
use. Generally "safe" or therapeutic doses of dexamethazone and other
similar drugs may potentiate elevated glucose levels in already
insulin-resistant horses. This might explain why certain horses founder
after receiving doses of these drugs that cause no problems in most equines.
Increased cortisol levels can also be
found in severely stressed or systemically ill horses. Many veterinarians
have dealt with "stress founders" and with founder following uterine or
other infections. Pollitt suggests that all these cases of laminitis share a
cause relating to insulin resistance rather than to strict endotoxemia.
Other researchers are also postulating that in cases of grain overload
founder, elevated glucose levels cause a "toxicity" that causes temporary
insulin resistance (so much glucose floods the system in such a short time
that the body cannot produce enough insulin to compensate). This insulin
resistance is intensified by elevated cortisol levels induced by endotoxemia
seen in these cases. If this part of the theory is proven correct then the
best method of treating or preventing laminitis is by treating or preventing
conditions that lead to insulin resistance. There are many current projects
looking at methods of doing that.
Insulin inhibits the breakdown of
triglycerides (fat) into free fatty acids (FFA) and glycerol. In the absence
of insulin this process of lipolysis can occur and FFA are released.
FFA are transported to the liver,
packaged as very low density lipoproteins (VLDL) and stored in adipose
tissue for potential later use. The cresty necked horses or overly fat
ponies seen in veterinary practices may well be insulin-resistant animals
and their body condition may be the first clue to their underlying
condition. The unification theory would suggest that it is not difficult to
now explain why these animals are at risk for laminitis in conditions that
other horses seem to tolerate well.
Just as in humans, there appears to be
a genetic component to type 2 diabetes and ponies, Morgans, other gaited
breeds and some Arabian bloodlines may be affected; though this research is
just beginning.
Promising
The practical advice available to
veterinarians and their clients from these new theories is the most
promising aspect of this research.
First an accurate diagnosis must be
made. Appropriate testing for Cushing's disease and hypothyroidism should be
done as these conditions may give a similar clinical appearance. Excellent
treatment is available in the form of Pergolide or thyroid replacement
hormone for these horses.
Blood glucose, insulin levels and a
glucose tolerance test may be needed to accurately diagnose a horse as being
insulin intolerant or diabetic. As in humans with type 2 diabetes, the first
step in treatment is management of the diet and an increase in exercise.
Many diabetics can be controlled for long periods of time with these simple
steps (see box). Additional drugs to control glucose levels are being
investigated and new treatment protocols will soon be suggested.
The most important point is to realize
that these horses are different and that their failure to respond to normal
treatments indicates the presence of a more important underlying
condition-insulin resistance. Success in treating any of the clinical
signs-laminitis, obesity, lethargy-will only come from addressing this
problem as well.
Dr. Marcella, a 1983 graduate of
Cornell University's veterinary college, was a professor of comparative
medicine at the University of Virginia. His interests include muscle
problems in sport horses, rehabilitation and other performance issues.
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