diabetes mellitus

• what are the three actions of insulin?

  inhibition of ketogenesis, stimulation of glucose and potassium uptake
• growth hormone is an important insulin antagonist and hence can cause insulin resistance
• The onset of DM is often insidious and the clinical course is chronic. Disturbances in water metabolism occur due to osmotic diuresis (the renal threshold for glucose is been exceeded) common clinical signs include…

  • PU/PD
  • Polyphagia (but some may have a decreased appetite)
  • Weight loss
  • Cataracts
  • Weakness
  • Lethargy

  Hepatomegaly may develop
• Pregnancy and dioestrus can predispose an animal to DM as the progesterone leads to a growth hormone from the mammary tissue leading to hyperglycaemia and then insulin resistance
• There are multiple pathogenic mechanisms responsible for the decreased insulin production and secretion. Commonly, this is due to the destruction of islet cells which can be secondary to immune destruction or severe pancreatitis.

  • Obesity predisposes to insulin resistance
  • Insulin resistance and secondary DM can occur in dogs that have hyperadrenocorticism or have been chronically administered glucocorticoids
• what are the two main aetiology (types) of DM in dogs?

  insulin deficient and insulin resistant
• Almost all diabetic dogs are insulin dependent, the exceptions are...

  • Bitches presenting in metoestrus with high levels of progesterone (inducing mammary origin growth hormone excess)
  • Dogs with concurrent Cushing’s disease may or may not be insulin-dependent
• Dogs that become diabetic during a metoestrus period...

  • If they had already lost insulin production –low basal insulin (due to glucose toxicity) they remained diabetic for the rest of their life.
  • If they had high basal insulin and therefore had maintained some islet function, they went into remission and their diabetes never came back after they were spayed.
• why do diabetic dogs get recurrent infections?

  there is immunological compromise and the local conditions favour microbial growth
• It is recommended to spay intact diabetic canine females to aid in insulin regulation (as insulin needs vary with their oestrus cycle). Also, Spays may be therapeutic in some cases e.g., metoestrus DM
• A diagnosis is based on persistent hyperglycemia and glucosuria (biochemistry and urinalysis). An elevated serum fructosamine test can also be done to help differentiate between stress-induced hyperglycemia and DM

  • Fructosamine concentrations will be normal in the stress induced patient
• If suddenly having a high energy day the dog will use up its glucose supply quickly causing hypoglycaemia. We may increase the food on these days (And oral glucose solutions/high sugar treats with easily soluble carbohydrates in preparation) but never stop insulin as we need to prevent ketoacidosis
• Treatment...

  • Insulin (injected once-twice a day)
  • Dietary management (high fibre and complex carbohydrates –avoid simple sugars)
  • Canine high-fibre diet reduces post-prandial hyperglycaemia
  • Diet also needs to be consistent while identifying the correct insulin dose as different diets have different effects on insulin
  • Oral hypoglycemic agents
  • Exercise is important too!
• Urinalysis is a standard part of PU/PD work-up

  • Glucosuria can indicate renal tubular damage and can occur with stress hyperglycaemia if it exceeds the renal threshold
  • Glucosuria without hyperglycaemia is not DM
• Other lab findings:

  • increased ALKP / ALT
  • increased cholesterol and triglycerides
  • Fasting hyperglycaemia
  • +/-hyponatraemia (Fluid is drawn out of cells which therefore dilutes sodium)
  • +/-ketonuria, ketonaemia
  • Fructosamine
  • Urine culture

  A pale swollen liver occurs in DM which can be seen PM or if operating hence some of the lab findings reflect liver damage
• fructosamine is the product of glucose binding to albumin
• Levels of fructosamine are dependent on the half-life of albumin and give an indication of glycaemic control over the preceding 2 - 3 weeks
• what temperature should insulin be kept at?

  2 - 8 C
• Two licenced products of insulin for dogs...

  • Caninsulin, MSD
  • Intermediate-acting preparation
  • Lente (mixed insulin zinc suspension)
  • Usually given twice daily but sometimes once
  • ProZinc, Boehringer
  • Protamine Zinc Insulin–insoluble component so has a longer duration of action
  • BID Cats, SID dogs
• Start the insulin treatment, giving 0.5 IU/kg sc BID and ask the owner to monitor water intake. See the dog back in 7 days and perform a 12-hour blood glucose curve if possible. If the control is sub-optimal, increase the dose by 10% and repeat the cycle until stable

  • 5% change is not noticeable
  • 20% change risks Somogyi effect

  If repeated BGC’s not an option, use a home diary and possibly fructosamine
• Insulin dosage should NEVER be adjusted on the basis of once daily urine glucose measurement as this can lead to the Somogyi effect.

  • Useful for documenting remission only
• a dog is havign a hypoglycaemic episode at home what sugar can be given via the mucosa?

  dextrose
• which diabetes type can dka occur in?

  type one (insulin-deficient)
• Senvelgo is not used in dogs but is an oral solution that can be used instead of insulin. This acts on the kidneys to control hyperglycaemia to reduce clinical signs and glucose toxicity. There will be a greater excretion of glucose in the urine. This is an oral hypoglycaemic drug and is helpful in type two (insulin-resistant) cases.

  • If used in type one DM, it can cause NEB, drive ketosis and possibly cause hypoglycaemia (ketoacidosis occurs).
• You may be able to reverse diabetes in cats by removing complex carbohydrates and moving on to a more suitable diet.
• with cats, insulin therapy may allow the pancreas to recover and the cat may enter remission meaning the continued administration of insulin can cause hypoglycaemia.

  • How long remission lasts is unknown.

  Urinalysis can be helpful to identify when the cat is coming out of remission and owners can do this at home, this allows for identification of DM coming back before the cat becomes systemically unwell.
• what stance in cats is typical of DM?

  plantigrade
• Type II diabetes (insulin-resistant type) is an inability to respond to insulin. cats often still have functioning beta cells at the time of diagnosis. Type II diabetic cats can often produce some insulin but peripheral antagonism or downregulation of insulin receptors results in uncontrolled hyperglycaemia.
• Persistent hyperglycaemia is a result of insulin resistance and abnormal insulin secretion, this then results in the syndrome of glucose toxicity. Glucose toxicity further contributes to the metabolic abnormalities of diabetes and can result in impaired insulin secretion and destruction and loss of beta cells. Prompt control of hyperglycaemia (i.e of the diabetic state) can resolve the problems associated with glucose toxicity and diabetes in cats can resolve.

  • We don't see this to the same degree in dogs.
• Persistent hyperglycaemia and glucosuria means that fat mobilisation is favoured leading to...

  • hepatic lipidosis
  • hepatomegaly
  • hypercholesterolemia
  • hypertriglyceridemia
  • increased catabolism
• what is the consequence of rapid weight loss in a cat?

  hepatic lipidosis
• the ideal diabetic diet for cats is...

  • high protein to normalise fat metabolism and provide a consistent energy source
  • restricted carbohydrates to reduce hyperglycaemia risk and glucose toxiciticty
  • wet formulation
• post-prandial hyperglycaemia is more common in which small animal species?

  dogs
• ideally blood glucose should be less than 14 mmol/l throughout the blood glucose curve
• when is the likely time a cat may enter diabetic remission?

  3 - 4 months
• Which underlying conditions in cats can lead to poor control?

  Obesity, acromegaly, Triaditis, pancreatitis, HAC, phaeochromocytoma, glucagonoma, UTI and significant dental disease and hyperthyroidism.

  • Compliance from the owner can also be a big concern
• What are the treatment options (insulin types) in cats?

  • Insulin Lente insulin (caninsulin) – 40-unit insulin
  • Protamine zinc insulin (prozinc) - 40-unit insulin
  • Glargine (Lantus) – 100-unit insulin that is unlicensed
  • Detemir (Levemir) - 100-unit insulin that is unlicensed
  • Oral hypoglycaemic drugs (not used in dogs)
  • Sodium-glucose transporter 2 inhibitors (velagliflozin / senvelgo and bexagliflozin / bexacat) promote renal losses of glucose.
  • others (less efficacy)
• Somogyi effect = rebound hyperglycemia.
• The Somogyi effect can occur when the blood sugar levels drop too low during the night or in between doses causing the body to respond by releasing other hormones (glucagon, cortisol and epinephrine) to cause a sharp increase in blood sugar levels. Hence hyperglycaemia can occur in the morning or after a hypoglycaemic event. Signs include…

  • Increased thirst and urination
  • Lethargy
  • Confusion 
  • Possibly signs of hypoglycaemia e.g., weakness, trembling or seizures just before the rebound event
• Diagnosis of the Somogyi effect involves careful monitoring of the glucose levels, especially during the night and management requires altering insulin dosage or timing or the feeding schedules.