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How to deal with concurrent pancreatitis and diabetes

in dogs and cats

How to deal with concurrent pancreatitis and diabetes

in dogs and cats

Linda FleemanAnimal Diabetes AustraliaBoronia Veterinary Clinic: 03 9762 3177 Rowville Veterinary Clinic: 03 9763 1799Lort Smith Animal Hospital: 03 9328 3021

L.Fleeman@AnimalDiabetesAustralia.com.au

Diabetes mellitusDiabetes mellitus�Glucosuria → osmotic

diuresis

�Compensatory polydipsia

�If can’t drink enough to compensate ���� dehydration

Diabetes mellitusDiabetes mellitus�↓ metabolism of absorbed

nutrients → tendency to lose weight

�Compensatory polyphagia�If can’t eat enough to

compensate → weight loss(+/- ketosis)

KetosisKetosis

�Catabolic state (fasting)

�Fat used for energy

�↑ Ketones (Ketosis)

�If exceed buffering capacity → Ketoacidosis

The ‘sick’ diabeticThe ‘sick’ diabetic

�Compensatory mechanisms (polydipsia and polyphagia) fail

�Dehydration

�Ketosis

Diabetic ketoacidosisDiabetic ketoacidosis

�Most common concurrent diseases

�Dogs: pancreatitis (Hume et al,

2006, J Vet Intern Med, 20:547)

�Cats: liver disease and pancreatitis (Bruskiewicz et al, 1997, J

Am Vet Med Assoc, 211:188)

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The ‘sick’ diabeticThe ‘sick’ diabetic

� i/v fluids (saline or Hartmanns)

�Insulin

PotassiumPotassium�Inappetence: ↓ intake

�Vomiting & diuresis: ↑ loss

�Acidosis: ↑ renal loss

�i/v fluids: dilution & ↑ renal loss

�Insulin: ECF→ICF

�Correction of acidosis: ECF→ICF

PotassiumPotassium

�Must add K+ to fluids�30-40 mmol/L

�KCl�50:50 KCl & KPO4

�Monitor plasma K+

Acute pancreatitisAcute pancreatitis�Non-specific presenting signs�Dogs: Inappetence, vomiting,

lethargy�Cats: Inappetence & lethargy

more common than vomiting�Clinical course is unpredictable�Outcome can be fatal�No specific treatment

Acute PancreatitisAcute Pancreatitis

� All diagnostic tests have limitations

� Definitive diagnosis requires histology of serial sections of the pancreas

Photos: R. Sutton

cPLI and fPLIcPLI and fPLI

�Pancreas-specific Lipase Immunoreactivity

�cPLI: Sensitivity ~80% and specificity ?

�fPLI: Sensitivity 67% and specificity ?

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cPLI and fPLIcPLI and fPLI

�Tests for pancreatitisor pancreatopathy?

Pancreatic ultrasonographyPancreatic ultrasonography

� Very specific test� 100% of dogs & cats without

pancreatitis will have normal ultrasound

� Reasonable sensitivity� ~67% of dogs & cats with

pancreatitis have changes on ultrasound

� Requires skilled operator

Treatment of acute pancreatitisTreatment of acute pancreatitis

Goals:

1. Support animal until there is spontaneous recovery

2. Manage clinical sequelae

DKA and acute pancreatitisDKA and acute pancreatitis

�Dogs: similar chance of survival as those with DKA alone, but require longer hospitalisation (Hume et al, 2006, J Vet Intern Med, 20:547)

�Cats: ?

DKA and acute pancreatitisDKA and acute pancreatitis

� i/v fluids (saline or Hartmanns) + K+

�Rehydration�↓ Ischaemia�↓ Glucose�↓ Ketones�↓ Acidosis

InsulinInsulin�Stop longer-acting insulin

�Use short-acting insulinwhile animal is in hospital (i.e. until eating well)

�Regular insulin (Actrapid®)

�Lispro insulin (Humalog®)

�(Glargine insulin)

Sears et al, ACVIM 2009

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InsulinInsulin�Constant rate i/v infusion�Repeated i/m injections�Simpler & less labour

intensive�Requires separate infusion

pump

Insulin CRIInsulin CRI1. 500 mL saline

2. Add 25 U insulin →50 mU/mL solution

3. Initial infusion rate: 50 mU/kg/hr (1 mL/kg/hr)

David Church’s protocol

Monitor blood glucoseMonitor blood glucose

�Aim for gradual decrease to 10-15 mmol/L

�Then, halve rate to 25 mU/kg/hr (0.5 mL/kg/hr) and switch maintenance fluids to 2.5% dextrose (+ K+)

Insulin / glucose balanceInsulin / glucose balance

25 mU/kg/hr (0.5 mL/kg/hr)

+

2.5% dextrose in 0.45% saline at

6 mL/kg/hr

Continuous glucose monitoring system (CGMS)Continuous glucose monitoring system (CGMS)

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Continuous glucose monitoring system (CGMS)

Continuous glucose monitoring system (CGMS)

Sensor Transmitter

Monitor

Glue

How to attach the CGMSHow to attach the CGMS

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Meter blood glucose readingsMeter blood glucose readings

� 2 hours after a new sensor is attached

� At a convenient time 2-6 hours after that

� Then every 12 hours

� Monitor will stop providing subcutaneous glucose readings if not calibrated with blood glucose readings

� Avoid calibrating meter when glucose is changing rapidly

How to obtain a blood glucose How to obtain a blood glucose measurement from the ear veinmeasurement from the ear vein When animal starts to eatWhen animal starts to eat

�Continue insulin CRI until appetite is normal

�Then start longer-acting insulin q 12 hours

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Chronic pancreatitisChronic pancreatitis

Chronic pancreatitisChronic pancreatitis�Permanent, irreversible damage

due to inflammation

�Histology: Fibrosis

�Recurrent episodes of acute pancreatitis?

Chronic pancreatitisChronic pancreatitis

�34% of dogsWatson et al, JSAP, 2007, 48: 609

�60% of cats�Correlated with age

de Cock et al, JVIM, 2007, 44: 39

�Clinical significance?

Does it matter?Does it matter?

� Associated with acute pancreatitis (& DKA)?

CatsCats�Importance of chronic

pancreatitis in diabetic cats is unknown

�Histological evidence of pancreatitis is frequent in non-Burmese diabetic catsLederer R, et al. J Vet Intern Med, 2004, 18: 443

DogsDogs�No studies of prevalence of

chronic pancreatitis in diabetic dogs compared with age (& breed?) matched controls

�5/17 (28%) of diabetic dogs: extensive pancreatic loss with fibrosis

Alejandro et al, 1988, JAVMA, 193: 1050

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Diabetes caused by chronic pancreatitis Diabetes caused by chronic pancreatitis

→ Loss of� insulin-secreting beta cells

� glucagon-secreting alpha cells

� exocrine acinar cells

� Loss of glucagon counter-regulation?

� ↑ risk of hypoglycaemia?

Loss of glucagon counter-regulationLoss of glucagon counter-regulation

Duesberg et al (1995) JVIM, 9, 181

� 7/12 diabetic dogs: impaired glucagon response to insulin-induced hypoglycaemia

� Clinical hypoglycaemia:� 5/7 dogs with impaired glucagon

response

� 0/5 dogs with a normal response

Sheeba: 8YO FS Labrador XSheeba: 8YO FS Labrador X

� Diagnosed with diabetes mellitus� Recruited for dietary trial� Stablisation: 10 mon� Dietary trial: 6 mon� No GI signs� Abdominal ultrasonography x5:

Normal pancreas

Sheeba: 8YO FS Labrador XSheeba: 8YO FS Labrador X

� Caloric requirement ~40% higher than median for other dogs

� Faeces with normal consistency passed 3 or more times /day

� 18 mon after completion of trial (34 mon after diagnosis of diabetes): typical clinical signs of EPI

Photos: T Price

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Photo: T Price

Islets in pancreatic remnantIslets in pancreatic remnant Sheeba: 8YO FS Labrador XSheeba: 8YO FS Labrador X

�10, 12, 14, 16 mon after diagnosis of diabetes: cTLI 0.9 µg/L (EPI:<2.5 µg/L)

�Marked hypertriglyceridaemia6.6-25.0 mmol/L (ref: 0.2-1.3 mmol/L)

ResultsResults�Association between fasting

hypertriglyceridaemia and exocrine pancreatic disease in 12 diabetic dogs (p=0.045)

HypertriglyceridaemiaHypertriglyceridaemia

�Exogenous insulin therapy will result in resolution of hypertriglyceridaemia in some diabetic dogs

�Others require dietary fat restriction in addition to insulin therapy

Monitor fasting triglycerideMonitor fasting triglyceride

�To identify persistent hypertriglyceridaemia

�To assess response to fat-restricted diet

Diagnosis of diabetes mellitus

History or clinical evidence of concurrent pancreatitis

Recommend dietary fat restriction (<30%ME)

Severe hypertriglyceridaemia

(>5.5 mmol/L)

Persistent hypertriglyceridaemia >4.4 mmol/L despite

good glycaemic control

Monitor body condition

Monitor fasting serum triglyceride concentration

Fasting triglyceride <4.4 mmol/L

Fasting triglyceride >4.4 mmol/L

Check glycaemic control and consider further dietary fat restriction (e.g. <20%ME)

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Dog loses body condition

Check glycaemic control and increase caloric intake at each meal

If weight loss continues despite good glycaemic control, consider evaluating exocrine pancreatic

function by measuring cTLI

Dog maintains body condition

cTLI <2.5 µg/L

Begin pancreatic enzyme

replacement

cTLI >5.0 µg/L cTLI 3.0-5.0 µg/L

Monitor cTLI and consider pancreatic enzyme replacement

Check for concurrent disease and consider increasing dietary fat

content

Monitor body condition

Monitor fasting serum triglyceride concentration Postprandial triglycerides?Postprandial triglycerides?

�Some dogs with postprandialhypertriglyceridaemia have normal fasting triglyceride level

�↑ postprandial triglycerides associated with ↑ cPLI (ACVIM 2008)

�Practical to measure TG during serial blood glucose curve

EPI in dogs recovered from acute pancreatitisEPI in dogs recovered from acute pancreatitis

� 4/30 (13%) had cTLI consistent with reduced exocrine function during 6 month follow-up

� 2/4 developed clinical signs of EPI� ↑ appetite � ↑ food intake (doubled)� weight loss� ↑ faecal volume

Sinclair JG, et al. 2006, JVIM, 20, 750