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!