Equine metabolic syndrome Pathophysiology

Question 1

What is equine metabolic syndrome?

Answer 1

Not a single disease, but a collection of risk factors for endocrinopathic laminitis
* Insulin dysregulation
* Prolonged hyperinsulinaemic response
* Postprandial
* Basal hyperinsulinaemia
* +/- hyperglycaemia
* Tissue insulin resistance
* Obesity (there are also lean animals with EMS)
* Laminitis

Question 2

What are the components of insulin dysregulation?

Answer 2

Question 3

Why is hyperinsulinaemia the most important factor? How can we reduce insulin concentration?

Answer 3

• Predictive of laminitis risk
• Hyperinsulinaemia is also causative of laminitis
• Therefore, reducing insulin concentration is key
  
  • Diet
  • Exercise
  • Medication

Question 4

Why is there not a set limit for insulin concentration that mean a horse will get laminitis?

Answer 4

No set insulin concentration -> laminitis
* Genetics
* Age
* Bodyweight
* Previous bouts of laminitis

Question 5

Is EMS like diabetes?

Answer 5

No… EMS =/= diabetes
However, prolonged high insulin can cause pancreatic beta cell exhaustion (not common)
* Hyperglycaemia
* PU/PD
* Weight loss
* Normal insulin concentration

Question 6

Why is pathophysiology important?

Answer 6

Diagnostic testing
- who to test
- which test to select
- what am i actually testing

Understanding laminitis risk

Management

Question 7

What are risk factors for EMS?

Answer 7

• Genetically predisposed breeds
  
  • Native breed ponies
  • Spanish-derived breeds
  • Warmbloods
• Obesity/regional adiposity
• Pregnancy associated ID
  
  • With or without hyperinsulinaemia

Question 8

What clinical signs are associated with EMS?

Answer 8

• ‘Easy keeper’/’good doer’
• Regional adiposity
  
  • Cresty neck
  • ‘Fat pads’
  • Sheath/mammary gland swelling
• Laminitis
• Divergent hoof rings

Question 9

What tests can you do to diagnose EMS?

Answer 9

Basal tests
* Basal insulin concentration - not sensitive
* Do not fast beforehand
* 1-3 hours after coming off pasture
* Not after big feed
* Can be used to assess response to diet change
* Adiponectin
* Adipose derived, insulin-sensitising hormone
* Low concentration associated with laminitis risk

Dynamic tests
* Oral sugar test (OST)
* (collect baseline insulin – optional)
* Administer oral Karo Light syrup (45 ml/100kg bwt)
* 60-90 min later collect blood – insulin and glucose
* Combined glucose insulin test (CGIT)
* Fast overnight, collect baseline insulin and glucose
* Administer IV glucose and insulin
* Frequent glucose sampling, insulin at 45min
* Glucose should be at baseline by 45min, insulin <100 iu/ml
* Similar to insulin tolerance test (ITT)

Question 10

What are you testing with the different diagnostic tests?

Answer 10

Insulin dysregulation:
* Prolonged hyperinsulinaemic response (OST or CGIT)
* Basal hyperinsulinaemia (Basal insulin concentration)
* +/- hyperglycaemia
* Tissue insulin resistance (CGIT)

Question 11

Why would you choose oral vs IV dynamic tests?

Answer 11

• Oral administration of glucose stimulates more insulin secretion than intravenous administration
• Oral administration simulates ‘real life’ more closely
• Oral glucose affected by other factors
  
  • Gastric emptying/gut transit
  • Absorption etc.
• CGIT cuts out enteroinsular axis

Question 12

What is the enteroinsular axis?

Answer 12

Ingestion of glucose -> incretins -> stimulate insulin release
* Gastric inhibitory peptide (GIP)
* GLP-1 - stimulates insulin release
* GLP-2 - increases glucose availability

Diet high in non structural carbohydrates decreases insulin sensitivity and ↓ adiponectin (insulin sensitising hormone)

Question 13

Why does laminitis occur?

Answer 13

• Hyperinsulinaemia causes laminitis
• Lengthening/stretching of secondary epidermal lamellae
  
  • Different to sepsis related laminitis
    
    • No destruction of basement membrane

IGF 1 upregulation changes musculoskeletal strength but multifactorial

Question 14

How can we assess risk of laminitis?

Answer 14

• Identify hyperinsulinaemia
• Dynamic tests
• Decreased apidonectin concentration
• Assess for concurrent risk factors
  
  • E.g. PPID
• Evidence of previous episodes
  
  • ‘Footy’
  • Divergent hoof rings

Question 15

How should you manage horses with EMS?

Answer 15

Diet
* Reduce carbohydrate intake - soaked hay
* Manage obesity

Exercise
* Increases insulin sensitivity
* Helps manage obesity to a degree

Medication
* SGLT2 inhibitors (ertugliflozin, canagliflozin)
* (Others e.g. levothryoxin)