ems notes - bivet.nu · laminitis tending to occur in certain susceptible individuals...

12/09/2013

1

Andy E Durham

“a collection of risk factors which indicate

an increased risk of coronary artery

disease”

12/09/2013

2

“a collection of risk factors which indicate

an increased risk of laminitis”

Laminitis = the equine heart attack!

Q: What do you get if you always do what you’ve

always done?

A: What you always got!

Henry Ford

EEEENDOGENOUSNDOGENOUSNDOGENOUSNDOGENOUSEEEEXOGENOUSXOGENOUSXOGENOUSXOGENOUS

SIGNALMENT CLINICAL CLINICOPATHOLOGICAL

1. age 1. obesity 1. IR/

hyperinsulinaemia

1. little exercise

2. breed 2. PPID 2. dyslipidaemia 2. dietary excess

3. gender 3. previous

laminitis

3. abnormal

adipokines

3. season

12/09/2013

3

• 40 laminitis cases (Donaldson et al 2004)

• 70% had PPID

• 23% had EMS

• 7% not tested

• 36 laminitis cases (Karikoski et al 2011)

• 31% had PPID

• 58% had EMS

• 11% no hormonal abnormality

LiphookEquine Hospital

93%93%93%93%

7%

89%89%89%89%

11%

ABOUT 90% OF LAMINITIS CASES HAVE AN UNDERLYING HORMONAL DISORDER

93%93%93%93%

89%89%89%89%

1. Laminitis occurring regardless of type (e.g. a young, fit TB)

◦ carbohydrate overload (grain engorgement)

◦ other endotoxaemic (retained placenta)

◦ weight bearing (post-fracture fixation)

2. Laminitis tending to occur in certain susceptible individuals

◦ endocrinopathic (PPID, EMS)

◦ pasture-induced laminitis

Type

1

Type

2

Insulin Resistance

HyperinsulinaemiaHyperglycaemia

(glucose intolerance)

compensatory

pancreatic secretion,

decreased insulin clearance

impaired glucose

uptake

stimulates

pancreatic secretion

receptor

downregulation?

12/09/2013

4

Insulin Resistance



impaired glucose

uptake

stimulates


receptor

downregulation?

compensatory



5 TREATED PONIES 4 CONTROL PONIES

• iv insulin infusion 0.36 mU/kg/h• iv saline infusion

• iv glucose infusion 0.34 g/kg/h

• mean serum insulin 1036 mU/L • mean serum insulin 15 mU/L

• mean plasma glucose 5.2 mmol/L • mean plasma glucose 5.2 mmol/L

• 5/5 clinical laminitis in 48 h • 0/4 laminitis

treatment:

response:

blood:

feet:

Insulin Resistance



impaired glucose

uptake

stimulates


receptor

downregulation?

compensatory



12/09/2013

5

EPIDEMIOLOGIC STUDIES

� Age

� Breed

� Gender

� Season

� Exercise

� Obesity (regional)

� Pasture

� PPID

Predispose to

hyperinsulinaemia

� Compared insulin responses to feeding:

◦ 12 normal horses vs 8 IR ponies

� H hay + ricebran

� H+G hay + ricebran + 0.75 g/kg glucose

IR ponies showed an

excessive insulinaemic response

to glucose

0

50

100

150

200

250

300

350

400

450

horses ponies

seru

m in

suli

n m

U/L

H H+G

Tinworth et al 2011

Borer et al 2012

0

100

200

300

400

500

600

700

800

900

1000

normal laminitic

seru

m in

suli

n m

U/L

resting insulin

peak insulin

Compared diet effects in 7 normal vs 5 laminitic ponies:

• Resting insulin

• Peak insulin after chaff + glucose

• laminitic ponies showed an

excessive insulinaemic response

to glucose

12/09/2013

6

� certain individuals may be prone to grass-induced laminitis

because of an excessive insulinaemic response to carbohydrate

ingestion

� Oral sugar challenge tests may directly mimic this effect

� Frank 2012

◦ Karo light corn syrup 15 mL/100 kg)

◦ measure serum insulin 60-90 mins later

◦ normal response < 60 mU/L


� fast overnight

� fasting insulin (optional)

� feed chopped chaff mixed with 1 g/kg BWT glucose/dextrose

� insulin measured 2 hours later

++++ ��


� 24 normal horses and ponies

� Compared with 367 submissions from horses and ponies with

history of laminitis (97 with fasting results also)

InsFmU/L

Ins120mU/L

Median normals <2.0 24.3

Median laminitics 9.9

P (Mann Whitney) <0.0001

InsFastmU/L

Ins120mU/L


12/09/2013

7


� 24 normal horses and ponies

� Compared with 367 submissions from horses and ponies with

history of laminitis (97 with fasting results also)

InsFastmU/L

Ins120mU/L


Median laminitics 11.5 199.0

P (Mann Whitney) <0.0001 <0.0001


Comparison of glucose challenge with fasting results:

� 97 submissions from horses and ponies with history of laminitis

with both fasting and 2 hr Insulin

n %

Fasting Insulin > 20 mU/L 23/97 24%

2 hour PG Insulin > 81 mU/L 75/97 77%

• requires a bolus of

5.0-10.0 g/kg

• effect occurs at

<1.0 g/kg

A. Dysfermentation of sugars disturbs the colon mucosal barrier leading to systemic absorption of “trigger factors” (carbohydrate overload model)

B. Absorbed sugars stimulate hyperinsulinaemia which then triggers laminitis (hyperinsulinaemic model)

12/09/2013

8

� Intake of 5% BWT (as dry matter) daily is high

� Non-structural carbohydrate (NSC) content of 20% is high

◦ 5% x 20% = NSC intake of 1% BWT daily = 10 g/kg

◦ = 10 g/kg NSC ingested over 16 h grazing

◦ = average 0.6 g/kg/h

????

?

The Liphook Equine Hospital

?

12/09/2013

9

• “good doing type”

• “eats nothing”

• “lives on fresh air”

• “puts on weight when he looks

at the grass”

• “I couldn’t feed him any less”

You have 2 choices:

1. Accept there is a problem

and deal with it

2. Wait for your horse or

pony to die prematurely

from laminitis

LAMINITIS RISK FACTORS

� Age

� Breed

� Gender

� Season

� Exercise

� Obesity (regional)

� Pasture

� (PPID)

CONTROL SOLUTIONS

� x

� x

� x

� extra care in spring/summer

� increase exercise

� control diet / increase exercise

� limit pasture access

� (see later!)

12/09/2013

10

1. Durham et al 2008

◦ 15 mg/kg q 12h

� significant decrease in insulin and glucose

2. Hustace et al 2009

◦ only 4 to 7% absorbed

3. Firschman et al 2009

◦ 15 mg/kg q 12 h normal horses

� no effect on insulin sensitivity (HEC)

4. Tinworth et al 2011

◦ 15 mg/kg q 12h IR ponies

� no effect on insulin sensitivity (FSIGT)

3.0

3.5

4.0

4.5

5.0

5.5

6.0

0 30 60 90 120 150 180 210 240

plasma

plasma

plasma

plasma glucose

glucose

glucose

glucose (( ((mmol/L

mmol/L

mmol/L

mmol/L)) ))

time posttime posttime posttime post----glucose (mins)glucose (mins)glucose (mins)glucose (mins)

No metformin

Metformin 30 mg/kg

Peak P=0.016

% increase P=0.047

AUC P=0.016

� 8 Ponies dosed with 0.5 g/kg

glucose,

� with and without 30 mg/kg

metformin 30 mins prior to

glucose

Rendle et al 2013

No metformin

Metformin 30 mg/kg

0

5

10

15

20

25

30

35

40

0 90 120 150

serum insulin (mIU/L)




time posttime posttime posttime post----glucose (mins)glucose (mins)glucose (mins)glucose (mins)

Ins 90 P=0.094

Ins 120 P=0.031

Ins 150 P=0.125

� 8 Ponies dosed with 0.5 g/kg

glucose,

� with and without 30 mg/kg

metformin 30 mins prior to

glucose

Rendle et al 2013

12/09/2013

11

� Metformin impairs glucose absorption in horses

� Metformin reduces insulin response to glucose ingestion

� Metformin might:

◦ aid weight loss by reducing sugar absorption

◦ protect against diet-induced insulin responses

• Comprises insulin resistance and obesity (at least)

• Represents a risk for laminitis (at least)

• May be suspected and diagnosed with relative ease

• Dietary management is crucial for improvement/reversal

• Exercise probably also helpful

• L-thyroxine (£££) and metformin (£) may also help

………the pony has a

greater hyperinsulinaemic

response.

12/09/2013

12

HyperinsulinHyperinsulinHyperinsulinHyperinsulin

----aemiaaemiaaemiaaemia

Native Native Native Native

BreedBreedBreedBreed

Regional Regional Regional Regional

ObesityObesityObesityObesity

Lack of Lack of Lack of Lack of

exerciseexerciseexerciseexercise

LAMINITISLAMINITISLAMINITISLAMINITIS

PPIDPPIDPPIDPPID

PasturePasturePasturePasture

Equine Metabolic Equine Metabolic Equine Metabolic Equine Metabolic SyndromeSyndromeSyndromeSyndrome

ems notes - bivet.nu · laminitis tending to occur in certain susceptible individuals...

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