Glucosuria osmotic diuresis Compensatory polydipsia If can t drink enough to compensate dehydration

Transcription

1 How to deal with concurrent pancreatitis and diabetes in dogs and cats Linda Fleeman Animal Diabetes Australia Boronia Veterinary Clinic: Rowville Veterinary Clinic: Lort Smith Animal Hospital: Diabetes mellitus Glucosuria osmotic diuresis Compensatory polydipsia If can t drink enough to compensate dehydration Diabetes mellitus metabolism of absorbed nutrients tendency to lose weight Compensatory polyphagia If can t eat enough to compensate weight loss (+/- ketosis) Ketosis Catabolic state (fasting) Fat used for energy Ketones (Ketosis) If exceed buffering capacity Ketoacidosis The sick diabetic Compensatory mechanisms (polydipsia and polyphagia) fail Dehydration Ketosis Diabetic 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) 1

2 The sick diabetic i/v fluids (saline or Hartmanns) Insulin Potassium Inappetence: intake Vomiting & diuresis: loss Acidosis: renal loss i/v fluids: dilution & renal loss Insulin: ECF ICF Correction of acidosis: ECF ICF Potassium Must add K + to fluids mmol/l KCl 50:50 KCl & KPO 4 Monitor plasma K + Acute 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 Pancreatitis All diagnostic tests have limitations Definitive diagnosis requires histology of serial sections of the pancreas cpli and fpli Pancreas-specific Lipase Immunoreactivity cpli: Sensitivity ~80% and specificity? fpli: Sensitivity 67% and specificity? Photos: R. Sutton 2

3 cpli and fpli Tests for pancreatitis or pancreatopathy? Pancreatic 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 pancreatitis Goals: 1. Support animal until there is spontaneous recovery 2. Manage clinical sequelae DKA 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 pancreatitis i/v fluids (saline or Hartmanns) + K + Rehydration Ischaemia Glucose Ketones Acidosis Sears et al, ACVIM 2009 Insulin Stop longer-acting insulin Use short-acting insulin while animal is in hospital (i.e. until eating well) Regular insulin (Actrapid ) Lispro insulin (Humalog ) (Glargine insulin) 3

4 Insulin Constant rate i/v infusion Repeated i/m injections Simpler & less labour intensive Requires separate infusion pump Insulin CRI 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 glucose Aim for gradual decrease to 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 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) 4

5 Continuous glucose monitoring system (CGMS) Sensor Glue Transmitter Monitor How to attach the CGMS 5

6 Meter 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 measurement from the ear vein When animal starts to eat Continue insulin CRI until appetite is normal Then start longer-acting insulin q 12 hours 6

7 Chronic pancreatitis Chronic pancreatitis Permanent, irreversible damage due to inflammation Histology: Fibrosis Recurrent episodes of acute pancreatitis? Chronic pancreatitis 34% of dogs Watson et al, JSAP, 2007, 48: % of cats Correlated with age de Cock et al, JVIM, 2007, 44: 39 Clinical significance? Does it matter? Associated with acute pancreatitis (& DKA)? Cats Importance of chronic pancreatitis in diabetic cats is unknown Histological evidence of pancreatitis is frequent in non-burmese diabetic cats Lederer R, et al. J Vet Intern Med, 2004, 18: 443 Dogs 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:

8 Diabetes caused by chronic pancreatitis Loss of insulin-secreting beta cells glucagon-secreting alpha cells exocrine acinar cells Loss of glucagon counterregulation? risk of hypoglycaemia? Loss of glucagon counter-regulation Duesberg et al (1995) JVIM, 9, 181 7/12 diabetic dogs: impaired glucagon response to insulininduced hypoglycaemia Clinical hypoglycaemia: 5/7 dogs with impaired glucagon response 0/5 dogs with a normal response Sheeba: 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 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 8

9 Islets in pancreatic remnant Sheeba: 8YO FS Labrador X 10, 12, 14, 16 mon after diagnosis of diabetes: ctli 0.9 µg/l (EPI:<2.5 µg/l) Marked hypertriglyceridaemia mmol/l (ref: mmol/l) Photo: T Price Results Association between fasting hypertriglyceridaemia and exocrine pancreatic disease in 12 diabetic dogs (p=0.045) Hypertriglyceridaemia 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 triglyceride To identify persistent hypertriglyceridaemia To assess response to fat-restricted diet History or clinical evidence of concurrent pancreatitis Monitor body condition Diagnosis of diabetes mellitus Severe hypertriglyceridaemia (>5.5 mmol/l) Recommend dietary fat restriction (<30%ME) Fasting triglyceride <4.4 mmol/l Persistent hypertriglyceridaemia >4.4 mmol/l despite good glycaemic control Monitor fasting serum triglyceride concentration Fasting triglyceride >4.4 mmol/l Check glycaemic control and consider further dietary fat restriction (e.g. <20%ME) 9

10 Monitor body condition Dog loses body condition Dog maintains 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 ctli <2.5 µg/l Begin pancreatic enzyme replacement ctli µg/l Monitor ctli and consider pancreatic enzyme replacement Monitor fasting serum triglyceride concentration ctli >5.0 µg/l Check for concurrent disease and consider increasing dietary fat content Postprandial triglycerides? Some dogs with postprandial hypertriglyceridaemia 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 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,