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Insulin Resistance
Discover the latest news on diagnosing and managing this problematic
condition.
By Shannon E. Pratt, PhD
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Insulin
resistance is an emerging problem in the equine industry because
it is associated with several equine conditions including Cushing's
Syndrome and Equine Metabolic Syndrome, a disease characterized
by obesity and recurrent laminitis.
Insulin is a hormone secreted by the ß-cells of the pancreas
in response to elevated blood glucose concentrations. For example,
after a horse eats a meal high in sugars and starches, blood
glucose levels rise, and insulin is released from the pancreas
when glucose levels are too high. Insulin's main function is
to stimulate tissues such as the skeletal muscle, liver and
adipose tissue to take up glucose from the blood, thereby returning
blood glucose concentrations back to normal levels. When insulin
does not stimulate glucose uptake effectively, it is termed
insulin resistance. This condition results in blood glucose
concentrations remaining higher than normal (hyperglycemia)
and can result in the pancreas secreting more insulin (hyperinsulinemia)
in effort to deal with the excess glucose. Furthermore, nutritionists
believe hyperglycemia causes inflammatory responses that may
be associated with laminitis, and eventually the pancreas may
wear out and not be able to produce insulin at all, resulting
in diabetes. Although true diabetes is rare in the horse, it
has been shown to occur.
Diagnosis of Insulin Resistance
Euglycemic Hyperinsulinemic Clamp (EHC) |
| Insulin
resistance can be diagnosed through quantitatively assessing
insulin sensitivity, defined as the ability of insulin to stimulate
glucose uptake. In both human and equine scientific studies,
the "gold standard" to assess insulin sensitivity
is the EHC (See Figures A and B). This test involves the intravenous
infusion of insulin into the bloodstream and the concurrent
infusion of glucose at a variable rate to maintain normal glucose
concentrations. It creates hyperinsulinemia because insulin
levels are higher than normal, but it maintains normal blood
glucose concentrations or euglycemia. The rate of glucose infusion
required to maintain normal glucose levels quantifies insulin
sensitivity. For example, a subject that is highly sensitive
to insulin will require more glucose to maintain euglycemia
because the glucose is rapidly leaving the blood and entering
the tissues; a subject that is less sensitive to insulin will
require less glucose because it will be staying in the bloodstream
and not entering the tissues. As you might guess, this is not
a very practical test for the average horseperson and veterinarian
to do because it takes three hours, requires specialized equipment,
several blood samples and a very patient horse! |
Obesity is associated with insulin resistance,
so if you have a horse that is a body condition score of greater
than 7, consider swapping dietary sugar for fiber sources.
Photo Courtesy of the Hooved Animal Humane Society. |
Minimal Model Analysis (MMA)
The MMA also tests insulin sensitivity; glucose and insulin
are administered intravenously, and their blood concentrations
are then measured and entered into a mathematical model (See
Figure C). Although it is a slightly less technical procedure
than the EHC, it is still time-consuming and requires a multitude
of blood samples.
Glucose
Tolerance Test
Another common test is the oral glucose tolerance test. Here
glucose is given orally via a nasogastric tube, and blood
samples are taken for up to six hours afterwards. However,
this test merely examines glucose tolerance. In other words,
it cannot distinguish between differences in glucose absorption
from the digestive tract, differences in insulin secretion
by the pancreas, or the uptake of glucose into tissues by
insulin-independent means (See Figure D). Thus, it is not
specific enough to quantify insulin sensitivity.
Other
Tests
In human medicine, it is common to take a single fasting blood
sample to determine blood glucose and insulin concentrations
without the influence of food. Although not a specific assessment
of insulin sensitivity, the information derived from these
tests has been well-correlated to results from the EHC and
the MMA. However, in horses, research has shown that a single
blood sample is not well-correlated with insulin sensitivity
(as determined by either the EHC or MMA). However, preliminary
data suggest that if three blood samples were collected on
different days (each after horses being without feed for 12
hours) and the averages of the glucose and insulin concentrations
found, there would be a stronger relationship to insulin sensitivity
than with a single blood sample.
The bottom line is that accurately quantifying insulin sensitivity/resistance
is a difficult process. In addition, this field is so new
that there is no magic number that indicates "insulin
resistant" compared to "normal" from a diagnostic
approach.
Causes
and Consequences
Insulin
resistance is likely caused from a variety of factors, but
diets high in starch and sugar have been shown to decrease
insulin sensitivity (increase insulin resistance). These diets
are absorbed as glucose when digested, which stimulates insulin
production, and nutritionists believe insulin receptors at
the tissues may become desensitized or even decrease in number
with frequent exposure to insulin caused by sugary foods.
Obesity is also associated with decreased insulin sensitivity,
as is Cushing's disease and recurrent laminitis. It should
be noted that it is unknown if insulin resistance is a predisposing
cause or a consequence of these conditions. For example, be
aware that although horses with Cushing's Syndrome may also
be insulin resistant, a horse that is insulin resistant may
not have Cushing's Syndrome. Weight loss and/or exercise have
been shown to improve insulin sensitivity.
It is obvious that more research is required in this field
to identify simpler tests to diagnose insulin resistance as
well as to clarify causes and consequences of this situation.
However, if you have a horse that is obese (body condition
score greater than 7), and/or suffers from chronic laminitis
or Cushing's disease, it would be prudent to adapt this horse
to a diet in which more of the energy is coming from fat sources
or fiber sources, such as hay, pasture, beet pulp or rice
bran, rather than from starch and sugar, such as grains and
molasses. More and more feed companies are coming out with
nutritionally balanced concentrate mixes that are designed
to have lower levels of starch and sugar. If possible, ensuring
adequate exercise should also help improve insulin sensitivity
in these horses. Check with your veterinarian, equine nutritionist
or feed dealer to determine the options that are suitable
for your horse.
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Figures
A and B
A. This graph shows typical glucose and insulin concentrations
during an EHC. Insulin concentrations are far higher (hyperinsulinemia)
than at rest (time 0) and glucose concentrations are clamped
at approximately 5mM (euglycemia).
B. This graph shows typical glucose infusion rates to
obtain euglycemia achieved in Figure A. A horse that is more
sensitive will require a higher glucose infusion rate to maintain
euglycemia than a horse that is less sensitive to insulin.
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Figure
C
This graph shows typical glucose and insulin concentrations
following an insulin-modified glucose tolerance test. Glucose
is infused at time 0, so glucose concentrations increase, followed
by a small increase in pancreatic insulin. At time 20, insulin
is administered resulting in a large increase in blood insulin
concentrations and an increase in glucose clearance rate. These
concentrations are used in the Minimal Model Analysis to quantify
insulin sensitivity.
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Figure
D
This graph shows typical glucose and insulin concentrations
following an oral glucose tolerance test where glucose is
administered orally. The clearance rate of glucose is determined
by absorption rate from the digestive tract, insulin secretion
from the pancreas, insulin and non-insulin mediated glucose
uptake by the tissues.
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Shannon
Pratt is from Toronto Canada where she grew up riding
and showing hunters through high school and college.
She has a PhD in Equine Nutritional Physiology from
University of Guelph, and she is currently an Assistant
Professor of Equine Science at Otterbein College in
Westerville Ohio.
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To
learn more about feeding Insulin Resistant Horses vistit Spillers
Seminole Horse Feeds.
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