Equine Metabolic Syndrome 2009

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REVIEW

Equine Metabolic Syndrome


Nicholas Frank, DVM, PhD, DACVIM

assumed that affected horses and ponies suffered from hy-


ABSTRACT
pothyroidism because they gained weight easily, became
Equine metabolic syndrome (EMS) is important because obese, and had enlarged adipose tissue deposits in the
of its association with laminitis. Obesity and insulin resis- neck and tailhead regions of their bodies. Low resting total
tance are two important components of EMS, and the un- thyroxine (T4) concentrations were detected in some af-
derlying cause of this syndrome is likely to be enhanced fected horses, which confirmed the association for many
metabolic efficiency. Affected horses are often referred to clinicians. However, the hypothesis that hypothyroidism
as ‘‘easy keepers’’ because they require fewer calories to induced this phenotype was never supported by results of
maintain body condition, and enhanced metabolic effi- research studies, and thyroidectomized horses failed to de-
ciency is an inherent risk factor for EMS that may be genet- velop obesity, abnormal adipose tissue deposits, or lamini-
ically determined. Pony breeds, Morgan horses, and Paso tis.3 Furthermore, horses with this phenotype responded
Finos are predisposed to EMS, but this problem can be normally when thyroid challenge tests were performed,
prevented through effective management. Overfeeding, and it was subsequently established that many nonthyroi-
abundant pasture grass, and inadequate exercise are risk dal conditions resulted in lower resting T4 concentrations.4
factors that relate to modern management practices. Obe- It can therefore be concluded that low resting T4 concen-
sity and adiposity induce insulin resistance, and recent re- trations are a consequence rather than a cause of EMS in
search suggests that this is the determinant of laminitis horses and ponies, and this finding reflects the abnormal
susceptibility in ponies. Increased plasma insulin concen- endocrine and metabolic status of the animal.
trations are detected in most affected horses and ponies, Equine metabolic syndrome represents a cluster of phys-
so this serves as a useful screening test for EMS. Physical iologic alterations that are important because of their asso-
characteristics also should be examined because horses ciation with laminitis in horses and ponies. It is useful to
with EMS exhibit regional adiposity in the form of a cresty group these problems together as a syndrome to prompt
neck or abnormal adipose tissue deposits close to the tail- the horse owner or veterinarian to evaluate the whole ani-
head. All horses with enhanced metabolic efficiency, obe- mal when laminitis is first detected. Evaluation of horses for
sity, or regional adiposity should be screened for EMS.
EMS also can be incorporated into annual or biannual
The combined intravenous glucoseinsulin test can be
wellness visits with the aim of preventing laminitis.
performed to diagnose insulin resistance in mildly affected
One area of confusion regarding EMS is its relationship
horses and quantify insulin sensitivity. Most horses with
with equine Cushing’s disease (ECD), which is also called
EMS can be effectively managed by reducing caloric in-
pituitary pars intermedia dysfunction (PPID). Some of
take, decreasing the starch and sugar content of the diet,
this confusion can be attributed to use of the term periph-
increasing exercise, and limiting or eliminating access to
eral Cushing’s syndrome. This term was first introduced in
pasture, but medical therapy is warranted in select cases.
the original description of EMS because it was hypothe-
Keywords: Obesity; Regional adiposity; Insulin resis- sized that affected horses synthesized more cortisol within
tance; Laminitis; Insulin their visceral adipose tissues, which has been referred to as
peripheral Cushing’s syndrome in humans.1 However, no
scientific evidence has been presented to support this
INTRODUCTION hypothesis, so it remains to be determined whether this al-
The term equine metabolic syndrome (EMS) was first intro- teration occurs in horses. Unfortunately, it was assumed by
duced by Johnson in 2002 to better define a condition that many that peripheral Cushing’s syndrome referred to ECD
was previously attributed to hypothyroidism.1,2 It was or PPID, and this led to confusion. In this review, EMS re-
fers to a condition of young and middle-aged horses that is
From the Department of Large Animal Clinical Sciences, University of Tennessee, completely independent of ECD. However, the author has
Knoxville, TN; and the School of Veterinary Medicine and Science, University of
Nottingham, Sutton Bonington, United Kingdom.
observed that horses with EMS are more likely to develop
Reprint requests: Dr. Nicholas Frank, Department of Large Animal Clinical Sciences, PPID, and this endocrinopathy develops at a younger age
2407 River Drive, Knoxville, TN 37996. in affected animals. Equine metabolic syndrome and
0737-0806/$ - see front matter
Ó 2009 Elsevier Inc. All rights reserved. PPID therefore can occur concurrently in middle-aged
doi:10.1016/j.jevs.2009.04.183 horses, and the risk of laminitis may increase at this time.

Journal of Equine Veterinary Science  Vol 29, No 5 (2009) 259


260 N Frank  Vol 29, No 5 (2009)

DEFINITION adiposity and increased laminitis risk. Leaner horses with


Components of EMS include obesity, regional adiposity, EMS usually fall into two categories: (1) horses that were
insulin resistance (IR), hypertriglyceridemia, and hyperlep- previously obese and are now being maintained in a leaner
tinemia, and this condition has been associated with in- body condition through effective management and (2)
creased laminitis risk, altered reproductive function, and leaner horses with regional adiposity, IR, and laminitis
seasonal alterations in arterial blood pressure.5-7 Although that do not test positive for PPID. The second category
no scientific evidence can be presented, it has been must be clarified through further research. Middle-aged
observed that colic caused by pedunculated lipomas is (1020 years) or older horses in this category are likely
more common in horses with EMS. to suffer from PPID that has not progressed to the point
of affecting diagnostic test results. Common diagnostic
PRESENTATION tests for PPID include measurement of adrenocorticotro-
pin hormone (ACTH) in the blood and the dexametha-
Obesity-Associated EMS sone suppression test. Both of these tests are likely to
The most common presentation for EMS is the obese have limited sensitivity when PPID is in its early or mild
horse with regional adiposity that develops laminitis while stages, so it is advisable to consider this possibility when ex-
grazing on pasture. An important underlying problem for amining middle-aged or older horses. Equine metabolic
many horses is the interaction between enhanced meta- syndrome can also develop in younger horses that remain
bolic efficiency and feeding practices on the farm. Affected lean overall. Regional adiposity, IR, and laminitis are de-
horses maintain body condition with a lower caloric intake tected; yet the animal is leaner across the ribs and top
and are often referred to as ‘‘easy keepers.’’ Increased ap- line. One potential explanation for this finding is that
petite may contribute to this condition, because obese affected horses have adipose tissues in certain regions of
horses with EMS seem to spend more time grazing. It is the body that are more metabolically active. Expansion of
likely that metabolic efficiency is determined in part by ge- adipose tissues in the abdomen is sometimes referred to
netics, and further research is required in this area. Only as visceral or omental adiposity in humans, and this condi-
one study has examined this question, and laminitis pre- tion increases fatty acid uptake into the liver, resulting in
disposition, which was associated with metabolic status, hepatic IR.11
exhibited a hereditary pattern in a closed herd of ponies.5
In the author’s experience, EMS is most commonly seen
PATHOPHYSIOLOGY
in pony breeds, Morgans, and Paso Finos, but the condi-
tion has also been detected in Arabians, Quarter Horses, Insulin Resistance
Saddlebreds, Tennessee Walking Horses, Thoroughbreds, Insulin resistance is the component of EMS that is most
and Warmbloods, indicating that many breed groups are likely to predispose horses to laminitis.5 This physiologic
affected.6 disturbance can be broadly defined as the failure of normal
Regional adiposity refers to the expansion of adipose tis- concentrations of insulin to induce the expected responses
sues in certain regions of the body. In humans, adipose in target tissues.12 The most important function of insulin
tissues expand around the waist or hips, whereas regional is to stimulate glucose uptake by tissues when nutrients are
adiposity occurs in the neck and tailhead regions of the abundant, such as after feeding. Skeletal muscle and adi-
horse.6,8 Adipose deposits are also detected in the prepuce pose tissues are the two major sites of insulin-mediated glu-
or close to the mammary glands in obese horses and occa- cose uptake, but the liver also responds to insulin by
sionally appear as randomly distributed subcutaneous increasing uptake of glucose from the blood. Insulin binds
masses along the sides of the abdomen. Expansion of adi- to receptors on the surface of plasma membranes and trig-
pose tissues within the neck region is proving to be the gers a series of internal events that culminate in the move-
best indicator of EMS in horses and ponies, and a scoring ment of glucose transporter 4 (GLUT4) proteins to the
system has been established to assess expansion of adipose plasma membrane, which facilitates rapid glucose uptake.13
tissues around the nuchal crest of the neck.9 This physical Insulin resistance may result from a reduction in the den-
characteristic is commonly referred to as a ‘‘cresty neck,’’ sity of insulin receptors, malfunction of insulin receptors,
and increased neck circumference has been associated defective internal signaling pathways, and interference
with IR in both horses and ponies.6,10 with the translocation or function of GLUT4 proteins.13
Laminitis predisposition may be determined by the abil-
EMS in the Leaner Horse ity of the body to supply glucose to hoof tissues.14 These
Equine metabolic syndrome is less commonly detected in tissues are likely to have a high requirement for glucose be-
leaner horses, and it is conceivable that affected animals cause remodeling processes are constantly active to main-
suffer from a different manifestation of the condition. tain dermoepidermal attachments. However, it is equally
The key features of EMS in leaner horses are regional likely that IR affects nutrient delivery to hoof tissues by
N Frank  Vol 29, No 5 (2009) 261

altering vascular tone. Insulin acts as a slow vasodilator in Obesity


the body, which increases blood distribution to muscles In humans and rodents, obesity is associated with elevated
when glucose is plentiful.15 Slow vasodilation occurs in re- free fatty acid (FFA) concentrations, altered adipokine pro-
sponse to insulin through the increased synthesis of nitric duction by adipose tissues, and elevated inflammatory
oxide (NO) from endothelial cells.16 However, insulin cytokine concentrations within the blood.25 Obesity and
also promotes vasoconstriction by stimulating endothe- IR are related to each other by the effects of higher FFA
lin-1 (ET-1) synthesis and activating the sympathetic ner- concentrations on insulin-sensitive tissues. As the move-
vous system. In the healthy state, activation of the insulin ment of FFAs into tissues increases with nutrient excess,
receptor stimulates two different signaling pathways within skeletal myocytes accumulate diacylglycerols that interfere
the vascular endothelial cell. Both the phosphatidylinositol with insulin signaling. This process is referred to as lipotox-
3-kinase (PI3K) and mitogen-activated protein kinase icity and can result in IR.26 However, humans vary in their
(MAPK) pathways are stimulated. The PI3K pathway leads genetic susceptibility to IR, so this process does not occur
to NO synthesis and vasodilation, whereas stimulation of in all cases. This may explain the observation that, although
the MAPK pathway increases ET-1 production and vaso- IR often accompanies obesity in horses, not all obese
constriction. Because it is the PI3K pathway that stimulates horses are insulin resistant.
glucose uptake, this pathway is likely to be compromised in A pro-inflammatory state also may be induced by obesity
the insulin-resistant animal.17 Hyperinsulinemia also may as monocytes move into adipose tissues in response to
contribute to vasoconstriction by increasing MAPK activ- monocyte chemoattractant protein-1 (MCP-1). Adipose
ity. It has recently been established that laminitis can be tissues secrete more MCP-1 as they reach their storage
experimentally induced in ponies by infusing insulin intra- capacity for lipid and become stressed.27 This increases
venously to create severe hyperinsulinemia.18 An increase the number of macrophages residing within adipose tis-
in plasma ET-1 concentration also has been detected in sues, and these inflammatory cells secrete tumor necrosis
blood collected from digital veins 12 hours after the factor alpha (TNFa).28 It therefore can be hypothesized
administration of carbohydrate to induce laminitis in that horses with EMS become more susceptible to laminitis
healthy horses.19 This finding suggests that digital vessels because TNFa secretion increases in response to obesity.
undergo vasoconstriction as a result of carbohydrate over- Vick et al27 examined 60 mares of varying body condition
load in horses, which may contribute to the development and found that obesity was associated with higher blood
of laminitis. If this is the case, horses with EMS may be interleukin-1 (IL-1) and TNFa mRNA expression and in-
more likely to develop laminitis when challenged by carbo- creased plasma TNFa concentrations. Higher plasma
hydrate overload, because vasoconstriction is already pro- TNFa concentrations have also been detected in previously
moted. Adhesion molecules on the surface of endothelial laminitic ponies with EMS, when compared with ponies
cells also may be involved in determining the risk of lamini- that did not have a history of laminitis.29
tis because insulin stimulates the expression of these mole- Obesity also affects adipokine production within adipose
cules through the MAPK pathway.20 Horses with EMS tissues, and this may impact the body as a whole. Adipo-
may be more susceptible to laminitis because they have kines are hormones produced by adipocytes that have local
a greater abundance of adhesion molecules on the endo- (paracrine) and remote (endocrine) effects on tissues. Lep-
thelial surfaces of their laminar vessels. tin and adiponectin are the best known adipokines, and
Platelet accumulation and activation play a role in the obesity has been associated with higher plasma leptin con-
development of laminitis in horses,21 and it is likely that centrations and lower plasma adiponectin concentrations
chronic IR enhances these processes. Weiss et al22 injected in horses.30 Lower adiponectin concentrations impair en-
radioactively labeled platelets into ponies and detected dothelium-dependent vasodilation in humans, but this
platelet accumulation distal to the coronary band with nu- relationship has not been established in horses.25
clear scintigraphy. Studies performed by Bailey et al21 and Finally, obesity may exacerbate the effects of laminar fail-
Menzies-Gow et al23,24 also demonstrated that endotoxin ure in horses because the downward forces on dermoepi-
and vasoactive amines activate platelets and increase pro- dermal attachments are likely to be greater in obese
duction of thromboxane and 5-hydroxytryptamine. These animals. This may increase rotation or sinking of the third
platelet-derived mediators induce vasoconstriction, which phalanx after laminitis.
reduces perfusion to the digit.23,24 The effects of EMS
on platelet function have not been studied in horses or Hepatic Insulin Resistance
ponies, but IR reduces NO synthesis by endothelial cells Hepatic insulin resistance could occur in obese and lean
in humans, and this vasodilator inhibits the aggregation horses with EMS if lipid accumulates in the liver as a result
of platelets.16 The ability of horses with EMS to withstand of elevated FFA concentrations.11 Lipid accumulation also
vasoconstriction triggered by endotoxin or vasoactive affects other liver functions, including bile excretion. Only
amines may therefore be impaired. limited evidence of hepatic IR has been presented in
262 N Frank  Vol 29, No 5 (2009)

horses. Higher gamma glutamyl transferase activities have The third situation can be addressed by examining plasma
been detected in some obese horses with EMS and mild he- glucose concentrations and detecting hyperglycemia,
patic lipidosis has been detected on post mortem examina- which occurs when horses develop diabetes mellitus.
tion in these cases (unpublished data). It has also been Blood samples should be collected from horses after the
demonstrated that leaner ponies with EMS have exagger- pain of laminitis has subsided. A short period of feed depri-
ated insulin responses to fructan when this carbohydrate vation (6 hours) is recommended before sample collection.
is provided in a meal, whereas healthy ponies fail to respond It was previously recommended that horses receive hay be-
to the same challenge.31 The liver plays a role in the metab- fore testing to reduce the stress associated with feed depri-
olism of fructose, so the response to fructan may be devel- vation. This recommendation was particularly important
oped as a diagnostic test for EMS in the future. for EMS horses with enhanced appetite. However, it is
now recognized that insulin concentrations are higher in
Pancreatic Insufficiency and Diabetes Mellitus some EMS horses after hay has been fed, so horses should
Most horses and ponies with chronic IR have elevated ideally be deprived of feed for 6 hours before blood collec-
blood insulin concentrations, indicating that the pancreas tion. If testing is to be performed in the morning, only one
is secreting more insulin to compensate for the reduction flake of hay (23 kg) should be left in the stall after 10:00 PM
in tissue action. However, it is also likely that reduced insu- the night before. When this approach is used, it is important
lin clearance by the liver contributes to hyperinsulinemia in to recognize that testing may have to be repeated with hay
horses with EMS. Portal blood circulates through the liver provided if the animal exhibits stress after feed deprivation.
before reaching the systemic circulation, and it is estimated Access to pasture and grain should always be withheld
that 60% of secreted insulin is cleared by the liver on first a minimum of 6 hours before blood collection.
pass.32 Hepatic IR therefore may contribute to hyperinsu- Hyperinsulinemia is defined by the reference range for
linemia in affected horses. the specific assay and the laboratory. For the University of
Pancreatic insulin secretion may decline after the horse Tennessee laboratory, hyperinsulinemia is defined by an in-
with EMS has spent many years in a state of compensated sulin concentration above 20 mU/mL (mU/L), which is
IR.33 This may be referred to as uncompensated IR, pan- approximately equivalent to 140 pmol/L (conversion fac-
creatic insufficiency, pancreatic exhaustion, or pancreatic tor of 7), and an arbitrary cutoff value of 100 mU/mL is
failure. Hyperglycemia develops in affected horses, and it used to define severe hyperinsulinemia. However, laborato-
is appropriate to refer to this as diabetes mellitus, which ries vary markedly, and different cutoff values for hyperinsu-
has been reported in the horse.34,35 In the author’s experi- linemia have been used to define IR in research studies.
ence, horses with diabetes mellitus have a leaner body con- Carter et al10 used a cutoff value of 32 mU/mL to predict
dition, and PPID has been suspected or confirmed in many the occurrence of laminitis in ponies, and Walsh et al38 de-
cases. Diabetes mellitus also may be associated with current fined EMS by an insulin concentration of 70 mU/mL. Cut-
or previous pancreatitis.36,37 off values of 110 mg/dL or approximately 6.0 mmol/L
(conversion factor of 18) are used to define hyperglycemia.
Other screening tests for EMS may be developed in the
DIAGNOSIS
future but are not currently available from diagnostic labo-
Screening Tests ratories. A panel of tests including leptin and high-molec-
Equine metabolic syndrome can be diagnosed by the his- ular-weight adiponectin, in addition to glucose and insulin,
tory, detection of obesity or regional adiposity, and test re- would improve diagnostic testing for EMS. A leptin con-
sults consistent with IR. Horses should be screened for IR centration greater than 7.3 ng/mL was used to predict
by collecting a blood sample and submitting plasma for laminitis in a recent study of ponies grazing on pasture.10
measurement of glucose and insulin concentrations. An
ACTH measurement can also be performed if PPID is sus- Combined Glucose-Insulin Test
pected in the middle-aged or old horse. Compensatory hy- This dynamic test provides a quantitative assessment of in-
perinsulinemia is a common feature of IR in horses and sulin sensitivity and should be used if EMS is suspected, but
ponies with EMS. Pancreatic insulin secretion increases the insulin concentration is within reference range. Horses
to compensate for a decrease in tissue effectiveness, so rest- should be kept off pasture and deprived of feed during the
ing serum insulin concentrations are elevated in horses test and for 6 hours beforehand. However, it is recognized
with moderate or severe IR. However, there are three situ- that some horses become very agitated when deprived of
ations in which this screening test is not helpful: (1) when feed, so hay must be fed to these animals to reduce stress
horses are painful and stressed as a result of active laminitis, and improve compliance with procedures. Hay with a lower
(2) at times when IR is mild and insulin concentrations are nonstructural carbohydrate (NSC) content is preferred.
still within reference range, and (3) when pancreatic insuf- Under ideal circumstances, the intravenous catheter
ficiency has developed as a consequence of prolonged IR. should be placed the night before testing to minimize
N Frank  Vol 29, No 5 (2009) 263

the confounding effects of stress. However, this procedure concentrations in horses with EMS. As stated previously,
can be performed on the same day in most horses. this finding reflects the metabolic status of the animal
A pre-infusion (baseline) blood sample is collected for and should be interpreted as a consequence rather than
both glucose and insulin measurements, and then 150 a cause of EMS.
mg/kg body weight (bwt) 50% dextrose solution is infused,
immediately followed by 0.10 units/kg bwt regular insulin
MANAGEMENT
(Humulin R; Eli Lilly, Indianapolis, IN).39 These dosages
are equivalent to 150 mL of 500 mg/mL (50%) dextrose Obesity Management
and 0.50 mL of 100 units/mL regular insulin for a horse It has recently been shown that obesity can be induced by
weighing 500 kg. Insulin should be drawn into a tuberculin overfeeding, and insulin sensitivity decreases as body fat
syringe and then transferred into a larger syringe containing mass increases.40,41 Obesity therefore should be corrected
1.5-mL sterile saline (0.9% NaCl) before infusion. Blood to improve insulin sensitivity. The first step in any weight
samples are collected at 1, 5, 15, 25, 35, 45, 60, 75, 90, reduction program is the elimination of all grain from the
105, 120, 135, and 150 minutes postinfusion. Additional diet. These feeds are not necessary for the obese horse and
blood is collected at 45 minutes and submitted with the contribute to the problem. If a treat is required, 1 cup low-
baseline sample to measure serum or plasma insulin concen- sugar/low-starch pellets can be fed. Another key to success
trations. At all other sampling times, a small volume of is limiting or eliminating access to pasture. Pasture grazing
blood (<0.5 mL) is collected from the catheter after draw- represents an unregulated source of calories that cannot be
ing off 3 mL waste blood. A drop of blood is placed on a test easily quantified. It is therefore necessary to limit pasture ac-
strip, and the blood glucose concentration is measured us- cess until weight loss has been achieved. Unfortunately,
ing a hand-held glucometer. many horse owners have difficulty accepting this approach
Both glucose and insulin responses are assessed when the because of the recognized benefits of pasture grazing. How-
combined glucose-insulin test (CGIT) is performed. Nor- ever, reluctant owners can be reassured that this is only a tem-
mal insulin sensitivity is defined by the blood glucose con- porary measure in most cases. The preferred approach for
centration returning to baseline or below by 45 minutes, inducing weight loss in obese horses is to temporarily elimi-
which means that the test can be performed in less than 1 nate pasture access and increase exercise. An alternative ap-
hour if the horse responds normally. When this glycemic proach is to reduce pasture access using one of the
response is being assessed, the first time that the concentra- following strategies: (1) confinement in a small grass pad-
tion falls below baseline is recorded for future reference. dock (size of a double tennis court), corner of a large pad-
Horses with IR take 45 minutes or longer to return to base- dock enclosed with electric fence, or round pen erected in
line. The insulin response is assessed by examining the in- the pasture (move twice weekly), (2) use of a grazing muzzle
sulin concentrations at baseline and 45 minutes later. to reduce grass consumption on pasture, and (3) limiting
Resting hyperinsulinemia is defined by a concentration of grazing time to 1 hour two or three times daily.
20 mU/mL, and the insulin response is judged to be exces- Exercise should be increased to accelerate weight loss and
sive if the concentration exceeds 100 mU/mL at 45 min- improve insulin sensitivity. Short-term exercise has been
utes. A higher insulin response indicates that more shown to improve insulin sensitivity in obese mares,42 and
pancreatic insulin secretion is necessary to compensate horses can be expected to lose weight at a faster rate when
for IR or that insulin clearance is impaired. exercised. Provided that the horse has recovered from lam-
There is a small risk of hypoglycemia when performing initis, a ‘‘more is better’’ approach can be taken for exercise.
the CGIT, so two 60-mL syringes containing 50% dextrose Trotting under saddle or on a lunge line for 30 to 60 min-
should be kept on hand and administered if sweating, mus- utes 5 days a week is an initial goal for obese horses.
cle fasciculations, or profound weakness are observed, or if Hay should be the primary source of calories until weight
the blood glucose concentration drops below 25 mg/dL. loss has been achieved. Ideally, the hay should be analyzed to
Note that pain and stress are important confounding vari- determine its nutrient composition and energy content. The
ables for the CGIT, so testing must be delayed until acute quantity of hay provided can be calculated using the digest-
laminitis has resolved. Horses that are easily stressed by ible energy value provided in the analysis, or a simpler ap-
procedures are more likely to have false-positive results. proach is to feed an amount equivalent to 2% of current
body weight. If weight loss does not occur after 30 days,
Thyroid Hormone Concentrations more stringent measures are required. Owners are advised
Lower serum T4 concentrations are sometimes detected in to reduce the amount of hay fed to 1.5% of current body
horses with EMS, and recent evidence suggests that this weight (eg, 8.2 kg for a 550-kg horse). After another month,
finding correlates with plasma insulin concentrations. the amount is lowered to 1.5% of ideal body weight. For ex-
Walsh et al38 recently reported a weak negative correlation ample, 15 lb hay should be fed per day to a horse with an ideal
(r ¼ –0.22; P < .001) between insulin and T4 body weight of 1,000 lb. It must be recognized, however,
264 N Frank  Vol 29, No 5 (2009)

that weight loss can be very difficult to achieve in horses or soaked in cold water for 60 minutes to reduce the soluble
ponies with EMS because of their high metabolic efficiency. sugar content. As stated previously, the relative importance
In a recent study of obese ponies, it was demonstrated that of NSC values is determined by the severity of IR. Mildly
energy restriction to 70%, 50%, and 35% of daily mainte- insulin-resistant horses tolerate hay with higher NSC
nance requirement was required to maintain average weight values, but this issue becomes more important if severe
loss of 1% body weight per week (18% of body weight was IR or diabetes mellitus develops.
lost across the 18-week study period).43 Ponies were fed Lean horses with EMS are more difficult to manage be-
a chopped mixture of alfalfa, hay, and straw twice daily, cause calories must be provided for weight maintenance or
and the total amounts of feed provided per day were equiv- gain, without exacerbating IR. This becomes even more im-
alent to 0.9%, 0.6%, and 0.4% of starting body weight for portant when horses are exercising and using more calories.
the 70%, 50%, and 35% energy restriction periods, respec- Feeding recommendations should therefore be tailored to
tively. These results suggest that very stringent diets may the individual horse and blood glucose and insulin concen-
be necessary in some horses and ponies with EMS. A vitamin trations monitored. Blood samples should be collected after
and mineral supplement meeting National Research Council a 6-hour period of feed deprivation to determine the resting
(2007) requirements should be provided when horses are status of the animal after 7 to 14 days on the new diet.
being maintained on a hay-only diet. Supplemental vitamin Within-horse comparisons between different feeds can be
E is recommended at a minimum dosage of 1,000 IU/day. made using this approach, although this is only necessary
for a small number of particularly challenging patients.
Management of Insulin Resistance Sweet feeds should never be fed to insulin-resistant
Obese horses vary in their degree of IR, with some horses horses because grains in these feeds contain large amounts
exhibiting severe IR and others maintaining normal insulin of starch, and molasses provides sugars in the form of su-
sensitivity. Those with normal insulin sensitivity may be in- crose, glucose, and fructose. Feeds that are primarily di-
herently tolerant of obesity. Alternatively, the amount of gested in the large intestine are preferred, and sugar beet
time spent in an obese state may be the more important de- pulp is an example. Molasses-free beet pulp can be fed to
terminant of insulin sensitivity in horses. In obese horses, insulin-resistant horses after being rinsed to remove sugars
IR is best managed by inducing weight loss. and soaked to prevent esophageal obstruction. However,
Feeds provided to insulin resistant horses also must be pelleted feeds containing beet pulp are now available to
examined to prevent dietary exacerbation of IR. The glyce- horse owners. These feeds are labeled as ‘‘low-starch/
mic response to the feed is important, which represents the low-sugar’’ products and are appropriate for most insu-
area under the blood glucose curve after a meal. Studies lin-resistant horses, although individual responses should
must be performed to examine glucose and insulin re- be monitored in severely affected animals.
sponses to different feeds in EMS horses, but it is advisable Feeding fat to insulin-resistant horses is controversial.
to lower the sugar and starch content of the diet. The car- Fats and oils are good sources of energy, but increased in-
bohydrate composition of the hay can be an important flux of fatty acids into muscle tissues has been implicated as
consideration when managing IR in horses, but the relative a cause of IR in humans.26 In a study of healthy mares, se-
importance of this factor depends on the severity of IR. rum nonesterified fatty acid concentrations decreased over
Many obese horses can be effectively managed by simply 5 weeks after addition of corn or rice bran oil to the diet,
inducing weight loss, whereas more intensive management and insulin sensitivity remained unaffected.44 Addition of
is required for severely insulin-resistant obese horses, those 0.5 cup (equal to 125 mL; contains approximately 100 g
with recurrent laminitis, and leaner horses with IR. When fat) rice bran oil or corn oil to the feed twice daily is there-
hay is to be tested, samples should be collected from several fore recommended when additional calories are required.
bales, preferably with a hay corer. A pooled sample then can
be sent to the Equi-analytical, Inc, laboratory (1-877-819- Prevention of Laminitis
4110; www.equi-analytical.com) for analysis. This test The decision to return a previously laminitic horse to pasture
costs approximately $27 for carbohydrate analysis (test is an important one. Two criteria should be used to make this
644), and the NSC content can be calculated from the re- decision: (1) whether the horse has returned to normal insu-
sults. Nonstructural carbohydrates are found inside plant lin sensitivity and (2) the likelihood that additional laminitis
cells and include simple sugars, starches, and fructans. episodes will occur. Many obese horses can be safely returned
Sugars and starches are most likely to exacerbate IR, so to pasture once weight loss has been achieved and IR has
the NSC value used in this case is calculated by adding resolved. In contrast, horses that have suffered multiple lam-
the starch and ethanol-soluble carbohydrate percentages initis episodes must be held off pasture indefinitely. Metabol-
provided in the report. It is currently recommended that ically efficient horses can be expected to gain weight and
EMS horses be fed hay containing less than 10% NSC. If return to an obese state when returned to pasture, so grazing
the NSC content falls between 10% and 12%, it can be must be limited in these animals.
N Frank  Vol 29, No 5 (2009) 265

The pasture is the most dynamic and most dangerous levothyroxine sodium per day for the same time period.
component of the diet if the horse has previously suffered Treated horses should be weaned off levothyroxine sodium
from laminitis. If an affected horse is returned to pasture, once ideal body weight has been attained by reducing the
use of a grazing muzzle is recommended to limit grass in- dosage to 2 teaspoons (24 mg) orally per day for 2 weeks
take. Grazing muzzles can be worn every day or only during and then 1 teaspoon (12 mg) orally per day for 2 weeks.48
months when the pasture grass is more abundant and con- Measured serum T4 concentrations are often elevated
tains higher concentrations of starches, sugars, and fructans. when levothyroxine is being administered, but concentra-
Turnout on pasture should be avoided when the pasture tions vary considerably within and between horses. Serum
grass is in a dynamic phase. These phases occur when the pas- T4 concentrations often range between 40 and 100 ng/
ture grass is growing rapidly in the spring after the weather mL in treated horses, indicating that levothyroxine sodium
turns warmer or during the summer after heavy rain. Tem- is being given at a supraphysiologic dosage. However, clinical
perate pasture grasses also accumulate sugar when they are signs of hyperthyroidism such as sweating or tachycardia have
stressed by drought or the onset of winter.45 When a horse not been observed in treated horses.46,49,50 Benefits of treat-
is returned to pasture after being confined to a stall for several ing horses with levothyroxine at lower dosages for longer pe-
days, reintroduction should occur gradually, with no more riods have not been evaluated scientifically. However, it was
than 1 hour of grazing at a time for the first 2 weeks. recently demonstrated that administration of levothyroxine
sodium at a dosage of 48 mg/day for 14 days prevented
healthy mares from developing transient IR in response to
TREATMENT the intravenous infusion of endotoxin.51 This finding sug-
Equine metabolic syndrome should be managed by reduc- gests that levothyroxine exerts a protective effect on insulin
ing caloric intake in obese horses, decreasing the starch and sensitivity when horses are challenged with endotoxin.
sugar content of the diet, increasing exercise, and limiting Insulin-sensitizing drugs including metformin and sup-
or eliminating access to pasture. However, medical therapy plements such as chromium and magnesium are also being
becomes necessary when IR persists after management evaluated as treatments for IR in horses. Positive responses
practices have been adjusted. Medical therapies also can to metformin have recently been reported.52 This drug is
be used as short-term interventions to accelerate weight available as Glucophage (Merck Santé S.A.S., Darmstadt,
loss or improve insulin sensitivity while management Germany) and is distributed in the United States by Bris-
changes are being implemented. This approach reduces tol-Myers Squibb Company. In the aforementioned study,
the likelihood of additional laminitis episodes occurring metformin was administered to insulin-resistant horses and
before management strategies have become effective. ponies at a dosage of 15 mg/kg twice daily by mouth. Proxy
Levothyroxine sodium (Thyro L, LLOYD, Inc., Shenan- measurements of insulin sensitivity improved in treated an-
doah, IA) can be administered to horses with EMS to accel- imals, without the adverse effect of hypoglycemia, but long-
erate weight loss and improve insulin sensitivity. Mean term results were variable. Metformin is a biguanide drug
body weight decreased and insulin sensitivity increased that enhances the action of insulin within tissues at the post-
when levothyroxine sodium was administered to healthy receptor level and inhibits gluconeogenesis within the liver.
mares at dosages ranging from 24 to 96 mg/day over 8 Results of this first clinical trial look promising, and metfor-
weeks.46 Long-term effects of levothyroxine on body min represents an option for the short-term management of
weight and insulin sensitivity also have been evaluated in leaner insulin-resistant horses. However, safety studies have
healthy mares over a 48-week period.47,48 Levothyroxine not been performed to date in horses, so this must be con-
sodium was administered to mares at a dosage of 48 mg/ sidered before the drug is prescribed long-term.
day, and glucose dynamics were measured at 0, 16, 32,
and 48 weeks. Echocardiographic evaluations, complete ACKNOWLEDGEMENTS
blood count, and plasma biochemical analyses were also
Research described in this review has been funded by the
performed at the same times to assess the safety of levothyr-
United States Equestrian Federation, Grayson Jockey Club
oxine. A greater than twofold increase in mean insulin sen-
Foundation, and Lloyd, Inc. (Shenandoah, IA), the manu-
sitivity was detected, and this mirrored a reduction in body
facturer of ThyroL.
weight. No adverse health effects were detected.
Sponsored by: McCauley Bros., Inc., Versailles, KY.
It is essential for horses to be placed on a controlled diet
when levothyroxine is prescribed because weight loss is
harder to achieve if the horse is permitted free access to pas-
ture. Levothyroxine sodium is administered by mouth or in
the feed at a dosage of 48 mg/day for 3 to 6 months to in-
duce weight loss, which is equivalent to 4 teaspoons per day.
Smaller ponies and Miniature horses can receive 24 mg
266 N Frank  Vol 29, No 5 (2009)

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