12/09/2013. Andy E Durham. a collection of risk factors which indicate an increased risk of coronary artery disease

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1 Andy E Durham a collection of risk factors which indicate an increased risk of coronary artery disease 1

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 ENDOGENOUS SIGNALMENT CLINICAL CLINICOPATHOLOGICAL 1. age 1. obesity 1. IR/ hyperinsulinaemia EXOGENOUS 1. little exercise 2. breed 2. PPID 2. dyslipidaemia 2. dietary excess 3. gender 3. previous laminitis 3. abnormal adipokines 3. season 2

ABOUT 90% OF LAMINITIS CASES HAVE AN UNDERLYING HORMONAL DISORDER 40 laminitis cases (Donaldson et al 2004) 70% had PPID 93% 23% had EMS

$(post-fracture fixation) 2.$

3 ABOUT 90% OF LAMINITIS CASES HAVE AN UNDERLYING HORMONAL DISORDER 40 laminitis cases (Donaldson et al 2004) 70% had PPID 93% 23% had EMS 7% not tested 36 laminitis cases (Karikoskiet al 2011) 31% had PPID 89% 58% had EMS 11% no hormonal abnormality 7% 93% 11% 89% Liphook Equine Hospital 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 Type endocrinopathic (PPID, EMS) 1 pasture-induced laminitis Type 2 impaired glucose uptake Insulin Resistance receptor downregulation? compensatory pancreatic secretion, decreased insulin clearance Hyperglycaemia (glucose intolerance) stimulates pancreatic secretion Hyperinsulinaemia 3

4 impaired glucose uptake Insulin Resistance receptor downregulation? compensatory pancreatic secretion, decreased insulin clearance Hyperglycaemia (glucose intolerance) stimulates pancreatic secretion Hyperinsulinaemia 5 TREATED PONIES 4 CONTROL PONIES iv insulin infusion 0.36 mu/kg/h treatment: iv saline infusion iv glucose infusion 0.34 g/kg/h response: mean serum insulin 1036 mu/l mean serum insulin 15 mu/l blood: mean plasma glucose 5.2 mmol/l mean plasma glucose 5.2 mmol/l feet: 5/5 clinical laminitis in 48 h 0/4 laminitis impaired glucose uptake Insulin Resistance receptor downregulation? compensatory pancreatic secretion, decreased insulin clearance Hyperglycaemia (glucose intolerance) stimulates pancreatic secretion Hyperinsulinaemia 4

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 g/kg glucose IR ponies showed an excessive insulinaemic response to glucose serum insulin mu/l H H+G 0 horses ponies Tinworthet al 2011 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 serum insulin mu/l resting insulin peak insulin normal laminitic Borer et al

certain individuals may be prone to grass-induced laminitis because of an excessive

mimic this effect Frank 2012 Karolight corn syrup 15 ml/100 kg) measure serum insulin

chopped chaff mixed with 1 g/kg BWT glucose/dextrose insulin measured 2 hours later +

horses and ponies with history of laminitis (97 with fasting results also) Ins Fast F

6 certain individuals may be prone to grass-induced laminitis because of an excessive insulinaemic response to carbohydrate ingestion Oralsugar challenge tests may directly mimic this effect Frank 2012 Karolight corn syrup 15 ml/100 kg) measure serum insulin minslater 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 + Liphook Equine Hospital 24 normal horses and ponies Compared with 367 submissions from horses and ponies with history of laminitis (97 with fasting results also) Ins Fast F mu/l Ins 120 mu/l Median normals < Median laminitics 9.9 P (Mann Whitney) < Liphook Equine Hospital 6

7 24 normal horses and ponies Compared with 367 submissions from horses and ponies with history of laminitis (97 with fasting results also) Ins Fast mu/l Ins 120 mu/l Median normals < Median laminitics P (Mann Whitney) < < Liphook Equine Hospital Comparison of glucose challenge with fasting results: 97 submissions from horses and ponies with history of laminitis with bothfasting and2 hrinsulin n % Fasting Insulin > 20 mu/l 23/97 24% 2 hour PG Insulin > 81 mu/l 75/97 77% Liphook Equine Hospital A. Dysfermentationof sugars disturbs the colon mucosal barrier leading to systemic absorption of trigger factors (carbohydrate overload model) requires a bolus of g/kg B. Absorbed sugars stimulate hyperinsulinaemia which then triggers laminitis (hyperinsulinaemic model) effect occurs at <1.0 g/kg 7

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 8

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!) 9

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.

0 plasma glucose (mmol/l mmol/l) 5.5 5.0 4.5 4.0 3.5 8 Ponies dosed with 0.5 g/kg glucose, with and without 30 mg/kg metformin 30 minsprior to glucose 3.

10 1. Durham et al mg/kg q 12h significant decrease in insulin and glucose 2. Hustace et al 2009 only 4 to 7% absorbed 3. Firschman et al mg/kg q 12 h normal horses no effect on insulin sensitivity (HEC) 4. Tinworth et al mg/kg q 12h IR ponies no effect on insulin sensitivity (FSIGT) 6.0 plasma glucose (mmol/l mmol/l) Ponies dosed with 0.5 g/kg glucose, with and without 30 mg/kg metformin 30 minsprior to glucose time post-glucose (mins) Peak P=0.016 % increase P=0.047 AUC P=0.016 No metformin Metformin 30 mg/kg Rendle et al 2013 serum insulin (miu/l) Ponies dosed with 0.5 g/kg glucose, with and without 30 mg/kg metformin 30 minsprior to glucose time post-glucose (mins) Ins 90 Ins 120 Ins 150 P=0.094 P=0.031 P=0.125 No metformin Metformin 30 mg/kg Rendle et al

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

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. 11

12 Native Breed Equine Metabolic Syndrome Pasture Regional Obesity Hyperinsulin -aemia PPID Lack of exercise LAMINITIS 12

ENDOCRINOPATHIC LAMINITIS

ENDOCRINOPATHIC LAMINITIS In recent published studies, Equine Metabolic Syndrome (EMS) and pituitary pars intermedia dysfunction (PPID) have collectively accounted for around 90% of laminitis cases seen in ambulatory practice.