Diabetes Mellitus and Insulinoma in ferrets

• What is the pancreas?

  • Mostly exocrine organ in mesentery close to proximal duodenum
  • Has some endocrine abilities
• What is the pancreas?

  • Has 2 lobes (right and left)
  • Each has duct attached to duodenum for enzymes to be released into GI tract
  • The smaller duct combines with common bile duct
• Structure of pancreas

  • Exocrine part consists of acini and endocrine consists of islets of Langerhans that exist between acini
  • Acini synthesize, store, and secrete digestive enzymes
• Structure of pancreas

  • Islets highly vascularized and innervated by vagal parasympathetic nervous system and splanchnic sympathetic fibers
  • Has 3 cells types
  • Beta cells- secrete insulin (70%)
  • Alpha cells- secrete glucagon (20%)
  • Delta cells- secrete somatostatin- and pancreatic- polypeptides
• Beta Cells and Glucose Uptake

  • Insulin produced in Golgi apparatus in cells, then packaged into granules
• Beta Cells and Glucose Uptake

  • GLUT-2 carries glucose into beta cells →increased intracellular concentration → betacell membrane depolarization due to influxof Ca2+ → exocytosis of granules
• Beta Cells and Glucose Uptake

  • Insulin production also influence by gastrin and secretin produced from duodenum
  • Epinephrine shuts down insulin production
  • “Flight or fight” response
• How Insulin Works

  • Insulin promotes glucose uptake into insulin-dependent tissues
  • Mostly muscle and adipose
  • GLUT-4 packaged in these cells in vesicles
• How Insulin Works

  • Insulin secreted due to hyperglycemia → binds to tyrosine kinase (insulin receptors) on cell surface → causes phosphorylation → vesicles released into extracellular space → GLUT-4 binds to glucose → brings it into cell
• How Insulin Works

  • K+ also needed for transport- reason currently unknown
  • Alpha cells also require insulin
  • Works opposite way and encourages to increase blood glucose concentrations
• Diabetes Mellitus

  • A metabolic condition in which the bodyis not uptaking glucose from the blood(i.e. causing hyperglycemia)
• Diabetes Mellitus

  • Normal range: 80-120mg/dL
• Diabetes Mellitus

  • 2 types of DM
  • Type I: insulin-dependent
  • Requires insulin therapy
  • Type II: non-insulin-dependent
  • Does not require insulin therapy
• Diabetes Mellitus

  • Dogs will ONLY have type I but cats are 50/50
• Diabetes Mellitus Type 1

  • Beta cells in pancreas are destroyed (trauma, autoimmune, severe inflammatory processes, etc.)
• Diabetes Mellitus Type 1

  • No beta cells= no insulin production
  • Unable to activate insulin-dependent cells for glucose uptake
• Diabetes Mellitus Type 2

  • Beta cells produce less insulin
  • Insulin-dependent cells also respond less
  • Causes inability for cells to uptake glucose
• Diabetes Mellitus Type 2

  • Happens secondary to obesity
  • Cortisol from stress can lead to weight gain due to excessive sugar production → reduces production of insulin →beta cells less likely to improve production when cortisol levels are normal
• Diabetic Ketoacidosis

  • When tissues are not able to get needed sugar, turn to another energy source
• Diabetic Ketoacidosis

  • Fat in liver is broken down for energy and creates ketones
  • Ketones decrease pH of blood (<7.0)
• Diabetic Ketoacidosis

  • Acidotic blood → electrolyte imbalances, cardiac suppression and arrhythmias, renal insufficiency
• Diabetic Ketoacidosis Clinical signs (common factors)

  • Dogs aged 4-14 years
  • Females 2x as likely as males
  • Cats can be any age
  • Neutered males most likely
• Diabetic Ketoacidosis Clinical signs (common factors)

  • Common breeds: toy poodles, schnauzers, keeshonds, cairn terriers, dachshunds, cocker spaniels, beagles, golden retrievers, labrador retrievers, pomeranians
• Diabetic Ketoacidosis Clinical signs

  • Nonketotic:
  • PU/PD
  • Weight loss (most common in cats
  • Polyphagia (always hungry)
  • Sudden cataract formation (only happens in dogs)
• Diabetic Ketoacidosis Clinical signs

  • Nonketotic:
  • Dehydration
  • Plantigrade posture in cats (walking on hocks)
• Diabetic Ketoacidosis Clinical signs

  • Ketotic:
  • Depressed/lethargic
  • Tachypnea
  • Weakness/unable to walk
• Diabetic Ketoacidosis Clinical signs

  • Ketotic:
  • Vomiting
  • Sickly sweet breath
  • Sometimes diarrhea
• Diabetic Ketoacidosis Physical exam

  • Depends greatly on if animal is in DKA or not
  • BAR-obtunded
  • Almost always obese
  • If not then significantly emaciated
• Diabetic Ketoacidosis Physical exam

  • Lethargic
  • Non-painful on physical
  • +/- mature cataracts
  • Ataxia (swaying) in back end- usually only cats
  • Overall ADR
• Diabetic Ketoacidosis Diagnostics

  • Full cbc/chem
  • Will see elevated glucose, +/- elevated K+, elevated ALP in dogs, elevated ALT and AST, +/- elevated phosphorus, falsely low Na+
• Diabetic Ketoacidosis Diagnostics

  • Full cbc/chem
  • CBC: NSF if nonketotic; ketotic- 50%non-regenerative anemia, neutrophilia,thrombocytosis
  • Rule out comorbidities or underlying causes
• Diabetic Ketoacidosis Diagnostics

  • Urinalysis- need AT LEAST a dip stick
  • Glucosuria (sugar in urine), +/- ketonuria (ketones in urine), +/- pyuria (WBCs), +/ hematuria (RBCs)
• Treatment (nonketotic)

  • Start on insulin therapy
  • Regular- fast response (often used more in emergencies)
  • 0.1-0.2U/kg IM every 1-2hrs until hyperglycemia improves
• Treatment (nonketotic)

  • Start on insulin therapy
  • NPH/Vetsulin/Prozinc- intermediate-acting
  • Dogs: 0.25-0.5U/Kg SQ SID-BID
  • Cats: 1-2 U/CAT SQ you DO NOT give by weight
• Treatment (nonketotic)

  • Start on insulin therapy
  • Glargine- long-acting
  • Best option for cats but very expensive
  • 0.25-0.5U/kg SQ BID
• Treatment (nonketotic)

  • Food therapy
  • Reduce carbohydrate intake (less sugars)
  • Some prescription brands have food for this
  • Cats can be managed on food alone
• Treatment (DKA)

  • EMERGENCY! Lack of treatment can be fatal
  • Start on IV fluids
  • Run usually LRS fluids (has K+ in it) for ~6hrs before starting insulin
  • Helps correct dehydration
• Treatment (DKA)

  • Potassium chloride (KCl) can be given as a CRI (constant rate infusion)
  • No more than 0.5 mEq/kg/hr
  • Phosphorus can be given too but not common
• Treatment (DKA)

  • Insulin therapy
  • IM: initial dose of 0.2 U/kg regular insulin, followed by 0.1 U/kg 1 hour later, adjust as needed to accomodate glucose concentration reduction
  • CRI: at vet’s discretion (there’s a very complicated equation involved)
• Monitoring

  • 4 different ways
  • Fructosamine level, Glucose curve, Freestyle libre, water intake