equine metabolic syndrome (geor)
DESCRIPTION
The term equine metabolic syndrome (EMS) is used to describe the clustering of obesity (and/or regional accumulations of fat), insulin resistance and increased susceptibility to laminitis in horses and ponies. In fact, EMS is now regarded as the most common cause of laminitis. This presentation will review the clinical features, diagnosis and medical management of EMS, and discuss dietary and exercise measures for mitigation of laminitis risk in affected animals.TRANSCRIPT
EQUINE METABOLIC EQUINE METABOLIC SYNDROMESYNDROME
Raymond J. Geor, BVSc, PhD, Dipl. ACVIM
Department of Large Animal Clinical SciencesCollege of Veterinary Medicine
Michigan State University
Presentation Outline
• What is Equine Metabolic Syndrome (EMS)?– Clinical features– Major complications (laminitis)
• Diagnosis– Assessment of insulin resistance
• Management– Dietary alterations– Physical activity– Medical management (brief)
Acknowledgments
Supported by Agriculture and Food Research Initiative competitive grant no. 2009-55205-05254 from the USDA National Institute of Food and Agriculture Animal Genome Program:
Integrated Research and Extension Program for Equine Metabolic Syndrome and Shivers
Krishona Martinson, Molly McCue, Stephanie Valberg, Nichol Schultz, Nicholas Frank, Ray Geor
Thanks to: Dr. Judy Marteniuk for facilitating discussion
What is equine metabolic syndrome?
• Term to describe obese, insulin resistant horses and ponies with apparent increased susceptibility to laminitis– Similarities with the human metabolic syndrome
• Other terms used– Obesity-associated laminitis– Peripheral Cushing’s syndrome– Prelaminitic metabolic syndrome
1. Increased adiposity generally (obesity) or in specific locations (regional adiposity)
2. Insulin resistance (IR)3. A predisposition to laminitis– Clinical or subclinical laminitis that has developed
in the absence of recognized common causes (e.g. colic, colitis, retained placenta, sepsis)
EMS – current definition
• Episode of laminitis often first clue • Clinical or subclinical laminitis – Association with grazing / changes in diet– Bilateral lameness attributed to sole
bruising or foot soreness after trimming – May be history of recurrent episodes
EMS – signs of laminitis
• Generalized obesity – Body condition score ≥ 7 (1 – 9 BCS scale,
Henneke system)– Obesity may be longstanding – Not all fat horses have EMS and not all
EMS horses are fat
EMS – Increased adiposity
• Regional adiposity (subcutaneous fat accumulations)– Nuchal ligament of neck, fat pads behind
shoulder, tailhead, prepuce or mammary regions
EMS – Increased adiposity
• Subjective scoring system to evaluate ‘cresty neck’ = fat mass in nuchal region (scale 0 – 5) Score ≥ 3 common in EMS
horses and ponies
Neck Crest Adiposity
Carter et al. Vet J 2009
• Laboratory evidence of insulin resistance and glucose intolerance – The hormone insulin regulates blood
glucose levels and stimulates glucose storage in tissues
– EMS – tissue response to insulin is decreased
EMS – Insulin resistance
Equine Metabolic Syndrome is a metabolic / endocrine disorder
Ins
Nervous SystemFetus
Skeletal muscle& adipose tissue
Insulin and glucose
metabolism
MetabolismOther functions
Glucose
GLU
T-1
GLU
T-1
GLU
T- 4
Ins
Ins Glucose
Nervous SystemFetus
GLU
T- 4
InsulinResistance
MetabolismVasodilation
Ins
Ins Ins
InsIns
GLU
T-1
GLU
T-1
HyperglycemiaType 2 diabetes
Skeletal muscle& adipose tissue
• High serum insulin concentration• Abnormal glucose and insulin
responses to oral or IV glucose
Evidence of insulin resistance
0 60 120 180 240 3000
50
100
150
200
250
EMSCon
Time (min)
Insu
lin (
IU/m
l)
Insulin response to oral glucose in EMS
1 2 3 4 5 6 7 8 9
0102030405060708090
100110120
Body condition score
Ser
um
insu
lin (
mU
/L)
Obesity & insulin resistance
Geor et al. 2007
300 horses
Breed & genetic predispositions?
• Breed predisposition?– Pony breeds, Morgans, Arabians, Paso
Finos• Genetics– EMS phenotype in dam-daughter pairs
has been described – Concept of ‘thrifty genes’ and the
‘easy keeper’ horse or pony– Subject of current USDA study
Genetics and EMS
GENOTYPE
METABOLIC SYNDROME obesity, insulin resistance and laminitis
“Thrifty” genes
ENVIRONMENT
Diet overfeeding high CHO dietsLow activity
“Easy keeper”
PHENOTYPE
Why increased susceptibility to laminitis?
• Directly related to insulin resistance?– High blood insulin induced laminitis in healthy
ponies and horses (Asplin et al. 2007)
– High insulin responses after ingestion of feeds and forages rich in nonstructural carbohydrates
• Indirectly related to obesity and insulin resistance?– State of chronic inflammation renders horse
more susceptible when exposed to trigger conditions e.g. grazing spring pasture
Jan March May July Sept0
100
200
300
400 EMS Normal ponies
*
*P<0.05 EMS vs. Con*
means sem
Ins
uli
n,
mIU
/L
Jan March May July Sept0
3
6
9
12
15
18 Water soluble carbohydrates Starch
0.00.30.60.91.21.51.8
% W
SC
or
ES
C
% S
tarc
h
Serum insulin in pasture-kept ponies – metabolic syndrome vs. normal ponies
Insulin values very high in some ponies in May: >500-600 mU/l
Treiber et al. 2008
ENVIRONMENTAL FACTORSEVALUATION OF INSULIN RESISTANCE EVALUATION OF INSULIN RESISTANCE IS KEY COMPONENT OF DIAGNOSTIC IS KEY COMPONENT OF DIAGNOSTIC
WORKUPWORKUP
Association between insulin resistance and risk for laminitis
STRATEGIES TO IMPROVE INSULIN STRATEGIES TO IMPROVE INSULIN SENSITIVITY IMPORTANT IN MANAGEMENTSENSITIVITY IMPORTANT IN MANAGEMENT
How is EMS Diagnosed?
• History– Pasture laminitis
• Physical examination– Increased adiposity
• Foot radiographs, other evidence of laminitis
• Blood tests– Assessment of insulin resistance
• Rule out other endocrine disorders– Equine Cushing’s disease
EMS vs. Equine Cushing’s
• Regional adiposity, hyperinsulinemia and laminitis also can be features of equine Cushing’s disease
• Presence of hirsutism, delayed coat shedding, sweating, polyuria suggest Cushing’s
• EMS and Cushing’s may occur concurrently, and some suggestion that EMS animals predisposed to Cushing’s
Diagnosis – Assessment of insulin resistance
• Static vs. dynamic tests of the glucose-insulin system
• Static– Single sample measurements of
blood glucose and insulin
• Dynamic– Combined glucose-insulin test (CGIT)– Oral sugar test (under development)
Resting insulin concentration
• High insulin (hyperinsulinemia) is an indicator of insulin resistance
Treiber et al. (2006) J Am Vet Med Assoc
• Many factors influence results and interpretation:– Stress, change in housing– Pain (laminitis), or recent feed change– Day-to-day variation– Type of assay
Recommendation for insulin
• Do not sample horses under pain/stress conditions
• Blood should be collected after a short feed deprivation period– No feed or hay overnight (~8 hours)– Collect blood in the morning (e.g. 8 am)
• Interpretation:– Hyperinsulinemia defined by an insulin
concentration > 20 - 30 µU/mL (fasted)
Management of EMS
• Nutrition– Obesity – dietary restriction
– Dietary carbohydrates
• Physical activity
• Medical management– Drug therapy
WEIGHT LOSS
Energy Intake < Energy Expenditure
Cut the calories
Increase physical activity
Creating Negative Energy Balance• Maintain reasonable feed intake BUT
decrease calorie content of diet
• Use late maturity grass hay (~800-900 kcal/lb)
• No grain or sweet feed (other ‘treats’)
• No pasture (uncontrolled calorie intake)
• Provide small amount of a ration balancer feed to meet nutrient needs– 1 to 1 ½ lb/day
Feeding for Weight Loss
• Feed hay as a % of BW• Start at 1.2-1.3% of BW – 1100-lb horse, 1.2% BW = 13 lb– 13 lb late cut hay @0.8 Mcal/lb = 10.5
Mcal/day• Equivalent to ~70-75% maintenance DE
needs– Divide into multiple smaller meals if
possible (boredom relief)
Weight loss in obese ponies
• Chaff-based diet at 1.0% actual BW as daily DM intake (70% DE needs)
Proportion of outset body mass
0 1 2 3 4 5 6 7 8 9 10 11 12
0.86
0.88
0.90
0.92
0.94
0.96
0.98
1.00
Week of study
Pro
po
rtio
n o
f o
uts
et b
od
y m
ass
Dugdale et al. 2010
Weight loss in ponies
• NO change in BCS over 12 week study• Linear reductions in intercostal fat (ultrasound) but
no change in rump fat depth, nor mid-neck circumference
Change in belly girth measurement
0 1 2 3 4 5 6 7 8 9 10 11 12
0.92
0.93
0.94
0.95
0.96
0.97
0.98
0.99
1.00
Week of study
Pro
po
rtio
n o
f o
uts
et b
elly
gir
th
Dugdale et al. 2010
Monitoring weight loss
Recommend serial measurements of heart and belly girths, neck circumference
Feeding for Weight Loss
Evaluate progress after 4 weeks– Expect ~5-6% decrease in
bodyweight vs. outset (e.g. weight tape measurement)
Approach to non-responders• Further decrements in hay amount/day– Lower to 1.0%, then to 0.7-0.8%
• Amounts <0.7-0.8% BW not recommended
Glucose / insulin responses to weight loss
Week 0 Week 6 Week 120
1020304050607080 Glucose
Insulin
Glu
co
se
(m
mo
l/L)
Ins
ulin
(m
u/L
)
Dugdale et al. 2010
Increased Physical Activity
• Important intervention in management of obese humans
• Probably helpful in obese, IR horses– Accelerate loss of fat, maintain
or increase muscle mass, modest increase in insulin sensitivity
– Combine with dietary restriction • How much? (volume/intensity)
Fat mass
Fat-free mass
20 kg decrease (~2%) in BW30 kg decrease in estimated fat mass
Carter et al., Am J Vet Res 2010
Effects of physical conditioning in obese horses fed at maintenance DE
Baseline Low intensity
High intensity
How and how much exercise? • Increased turnout for
confined horses– Large dry lot
• Structured exercise– Start 3-4 days per week,
~10-15 min riding or on a lunge line
– Increase frequency and duration
• Good surface, close attention to feet
Control of Dietary Nonstructural Carbohydrates in Insulin Resistance
• Insulin resistance lowers threshold for laminitis when EMS horses and ponies fed high NSC forage, grains, sweet feeds
• Some animals extremely sensitive to NSC variations even when obesity well managed
Pasture access
• Pasture represents:– Unregulated caloric intake– Increased risk of laminitis triggering
eventsRecommendation• Eliminate pasture until IR resolved • Return the horse to pasture if only the first
laminitis episode – once obesity and IR have resolved
• Recurrent laminitis cases – permanently off pasture or restrictions when pasture growing or stressed
Options for pasture turnout
• Restricted grazing time – 1-2 hours per day– Beware the “Hoover” pony – consume
~40%+ of typical daily dry matter intake in 2-3 hours!
• Restricted grazing area– Limit area of turnout – round pen, corner
of paddock, or strip grazing with electric fence
• Turnout with grazing muzzle
Options for pasture turnout
Choosing forages/alternatives for insulin resistant horses
• NSC content of forage <10%– Direct measurement needed e.g. Equi-Analytical
• Pre-feed soaking in water to remove water-soluble carbohydrates (sugars, fructans)
• Forage alternatives e.g. beet pulp– Can be simpler approach to controlling NSC
• Commercial specialty products– Known NSC content, alternative sources of
digestible energy
Soaking hay can help but not a panacea
Longland et al. J Eq Vet Sci 2009
Hay Original WSC
(g/kg DM)
20 min % WSC loss
40 min % WSC loss
3 hr % WSC loss
16 h % WSC loss
Orchardgrass 230 4 5 6 24Ryegrass 135 4 15 22 24Timothy 221 3 12 15 40Ryegrass 124 8 26 43 44Mixed hay 187 2 5 12 19Poor quality 123 2 2 6 9First cut, mixed hay
167 8 18 18 54
Some forages remained >10% (100 g/kg DM) after 16 h soaking
• Low NSC hay remains foundation of ration
• Boost calories by:– Increasing forage (>2% bwt.)– Adding non-molassed beet pulp and/or– Adding commercial low NSC feed and/or– Adding vegetable oil (½ cup – 1 cup/day)
• Small meals to limit glycemic and insulinemic responses
Feeding non-obese EMS horses
Value of supplements?
• Magnesium, chromium, cinnamon– Lots of anecdote to suggest
benefits but not much science
– NOT a substitute for dietary restriction and exercise
Medical management
Indications• Reserved for horses that do not
respond to diet/exercise management (minority of cases)
Concerns• Medical treatment initiated without
other changes– Not a substitute for diet and other
management changes
Levothyroxine sodium(Thyro-L®)• Enhances weight loss and
improves insulin sensitivity
• Administer 48 mg/day PO (500 kg horse) for 3 to 6 months
Frank et al. (2008) Am J Vet Res
Metformin(Glucophage®)• Lowers serum insulin
concentrations and proxy measures of IR
• Administer 15 mg/kg PO q8 to 12h
Durham et al. (2008) Equine Vet JHustace et al. (2009) Am J Vet Res
These medications must only be given under the supervision of your veterinarian
How you can get involved with EMS research
• Visit University of Minnesota website http://www.cvm.umn.edu/equinegenetics/ems/home/html
• Goals of website1. Education and outreach for horses owners and
veterinarians managing EMS horses and ponies
2. Online patient database for collecting and storing data on EMS horses (and control, non-affected animals)• Your horse/pony can participate!
USDA Project on EMS – led by Drs. Molly McCue and Nichol Schultz
• Goal is to determine the role of genetics in EMS and associated susceptibility to laminitis– Aim to identify genetic markers of EMS so that
susceptible horses can be identified before they develop laminitis
• Getting involved1. Complete online surveys to determine eligibility
2. Work with your veterinarian to collect blood samples from EMS and control horse or pony• Store DNA for genetic analysis
• Endocrine and metabolic data (e.g. insulin) analyzed at no cost, with data reported back to you
• Especially interested in Morgan horses and Welsh ponies but other breeds are fine
EMS Take Home Message
• Combination of obesity (generalized and/or regional), insulin resistance increases risk of laminitis
• Problem can be controlled – Early identification and corrective management– Likely remain susceptible to laminitis
• Obesity and insulin resistance are primary targets in management– Weight loss, lower NSC diets– Restricted pasture – Physical activity
Thank you for participating in this webinar!