Canine diabetes mellitus Flashcards
Outline the effects of insulin?
What are the actions of insulin after injection?
Describe the types of diabetes as stated by WHO?
Type 1: (beta–cell destruction, usually leading to absolute insulin deficiency)
- Immune-mediated (including LADA)
- Idiopathic
Type 2: (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance)
What are some of the sources of type and type 2 diabetes?
Production (~Type 1)
- Pancreatectomy
- Pancreatitis
- Auto-immunity
- Islet cell hypoplasia
- Chemical toxicity
Target (~Type 2)
- Progesterone/agen (females more common)
- Growth hormone
- Glucocorticoids
- Glucagon
- Catecholamines
- Thyroid
- Obesity
What is the aetiology of canine diabetes mellitus?
Insulin-deficient (Type 1 like):
- Immune-mediated (probably common)Antibodies in circulation against islet Ag
- (e.g. insulin, GAD-65, insulinoma antigen-2
- DLA subtypes predisposed (MHC)
- (Samoyed, Tibetan Terrier)
- b loss due to EPI / pancreatitis (probably common)
- Congenital b loss (rare)
Insulin-resistant (Type 2 like):
- Progesterone (e.g. metoestrus) - an acromegaly (common)
- Hyperadrenocorticism, exogenous corticosteroids
- IGF-1/GH excess (pituitary acromegaly extremely rare)
Almost all diabetic dogs are insulin dependent
Exceptions include:
- 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
- If not treated irreversible beta-cell damage is likely to occur and the dog will become IDDM
What is the clinical presentation of diabetes mellitus?
DM is generally a disease seen in older dogs
- Peak age of incidence is 7 – 9 y/o
- Female > male cases by approx 2:1
Juvenille-onset DM has been reported but is rare
- Usually develops < 1 year of age
Name some breeds predisposed to DM?
- Australian terrier
- Standard schnauzer
- Miniature schnauzer
- Bichon frise
- Spitz
- Fox terrier
- Miniature poodle
- Samoyed
- Cairn terrier
- Keeshond
- Maltese
- Toy poodle
- Lhasa apso
- Yorkshire terrier
- Collie
- GSD
What is the usual clinical presentation of diabete mellitus in the dog?
Classic presentation of “starvation in the midst of plenty”
- Polyphagia but losing weight (insulin is required in hypothalamic satiety centre as this has an insulin dependent mechanism that recognises how much)
- Polydipsia and polyuria (osmotic diuresis)
- Quickly tired/poor exercise tolerance/sleepy
- Diabetic cataracts
- Recurrent infection (e.g.UTI)
- “Acetone” breath
- Most owners therefore present due to nocturia/urinary incontinence
- Occasionally present due to “sudden onset blindness”
What is the pathophysiology of the clinical presenting signs of diabete mellitus?
Pathophysiology
- Polyuria, polydipsia
- Osmotic diuresis
- Polyphagia
- Insulin in CNS – hypothalamic satiety centre
- Weight loss/exercise intolerance/lethargy
- Negative energy balance
- Reduced glucose and AA uptake
- Recurrent infection (esp. UTI (glucose in urine feeds the bugs, conjunctivitis)
- Immunological compromise
- Local conditions favour microbial growth
- Ketotic breath (smells like acetone (nail varnish remover))
- Ketogenesis
- Cataracts
- Osmotic effects
How are diabetic cataracts formed?
WHEN GLUCOSE NOMALLY GETS IN LENSE IT IS METABOLISED BY HK WHEN TOO MUCH GLUCOSE A DIFF PATHWAY METABOLISED EXCESS GLUCOSE AND THIS DRAWS WATER INTO THE LENS.
How can an acute clinical presentation manifest?
Occasionally the first signs of illness are acute when the dog develops diabetic ketoacidosis (DKA)
- Dull, depressed, weak, possibly comatose
- Often vomiting
- Dehydrated
- IV fluids and critical care
Ketonuria/ketotic breath ≠ DKA
- If eating and drinking – still straightforward management
How should diabetes be investigated?
Urinalysis standard part of PU/PD work-up
- Glucosuria
- Glucosuria without hyperglycaemia is not DM (renal tubular disease)
Other lab findings:
- Raised ALKP / ALT (liver swollen with metabolic activity)
- Raised cholesterol, triglycerides
- Fasting hyperglycaemia
- +/- hyponatraemia
- +/- ketonuria, ketonaemia
- Fructosamine (GOOD MEASURE FOR DIABETIC CATS due to stress hyperglycaemia it is more clear cut in dogs)
- Urine culture
How can diabetes melltius be diagnosed in the canine?
- Hyperglycaemia
- fasting hyperglycaemia
- >12mmol/l usually
- >5.5 – 12mmol/l more challenging
- Glucosuria
- Renal threshold ~ 10-12mmol/L
- +/- Ketonuria
- Fructosamine
- The non-enzymatic binding of glucose 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
- ? Accuracy
- Useful but be careful when interpreting results
- A fructosamine of > 400mmol/l is highly suggestive of diabetes mellitus
- Differentiates long term high glucose from short term high glucose (e.g. stress hyperglycaemia
- Caution (false negatives) if PU/PD history very recent
What are the aims of treatment?
- Prevent life threatening ketoacidosis
- Abolish clinical signs
- Restore lost condition/weight
- Reduce risk of complications
With regards to treatment and the dog is IR what needs to be considered when treating?
Insulin
- Type and frequency of administration
Diet
- Must be carefully assessed
Body condition
Lifestyle
- Availability for 12hourly injections
- Availability for monitoring (e.g., hypoglycaemia)
- Ongoing costs
When to spay intact female
What is the licensed insulin for dogs?
- One licenced product for dogs
- Caninsulin, MSD
- Intermediate acting preparation
- Lente (mixed insulin zinc suspension)
- Usually given twice daily but sometimes once
- Initial dose 0.5 iu/kg BID
- Most patients require between
- 0.8 – 1.2 iu/kg/dose to stabilise
- 40IU/ml – must use companion syringes with vial product
- Owners must be counselled regarding their handling of insulinInsulin should be kept between 2-8oC
- Fridge door often best (unless internal freezer)
- The insulin should not be shaken, just gently rolled prior to drawing up dose
- Insulin beyond its expiry date may be ineffectual
- Manufacturers recommend discard bottle after 28 days in use
Discuss why diet is so essential when managing diabetes?
- Incorrect diets / titbits / scavenging can all play havoc with stabilisation
- Usually feed 2 times a day with BID dosing
- Feed twice a day with SID dosing
- Calculate the patients energy requirements and ensure being fed correct amount
- [(30 x BW) + 70] x illness factor = MER (kcal)
- Foods should be high in complex carbohydrates to minimise post-prandial glucose peaks
- Food should be high in fibre
- If possible, owners should be encouraged to feed one of the “glucomodulation” diets
- Weight reduction diets can be helpful but should not be used in thin patients
Why should diabetic females be neutered after they are stabilised?
Yes as progesterone effects DM. Seasons give massive spikes in progesterone meaning more insulin must be given and this is hard to titre down quickly enough to prevent ketoacidosis.
How does mark recommend you treat DM?
- Start the insulin treatment, giving 0.5 IU/kg sc BID
- Make sure the diet is correct and consistent
- Ask the owner to monitor water intake
- See the dog back in 7 days and perform a 12-hour BGC if possible
- If control sub-optimal, increase dose by 10% and repeat cycle until stable
- 5% change not noticeable,
- 20% change very large and risk Somogyi
- If repeated BGC’s not an option, use home diary and possibly fructosamine
How should DM treatment be monitored?
Trust the patient and owner
- The owner will quickly become an excellent judge of their dog’s diabetic control
- Water intake, appetite, weight and demeanour
- Diabetic diary - paper, online app.
Blood glucose curves
- Tells you what effect the insulin is actually having
- Arent always the definitive answer to treatment. Depends on when you test!!
Interpret these blood glucose curves?
What is the Somogyi overswing?
Response to insulin - Some animals will show signs of marked hypoglycaemia after administration of insulin but then begin to show signs of polyuria/polydipsia. If the dose is too great for the animal, antagonistic hormones will be released that will result in a rebound hyperglycaemia after a period of hypoglycaemia, a phenomenon called a Somogyi overswing. This is remedied by reducing the dose of insulin given to prevent the release of antagonistic hormones.
What other techniques are available for monitoring DM?
Fructosamine
- The non-enzymatic binding of glucose 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
- Aiming for approx 400 - 450 nmol/l – excellent!
- “normal” fructosamine suggests significant periods of hypoglycaemia
Glycated haemoglobin (GHb)
- Glucose non-enzymatically bound to haemoglobin
- Gives an indication of the glycaemic control over preceding 2-3 months
- Used in human medicine
- Value in veterinary species not clear
- GHb stabilised diabetic 4-6%
- GHb poorly stabilised diabetic >7%
Urine testing
Opinion:
- Insulin dosage should NEVER be adjusted on the basis of once daily urine glucose measurement
- Somogyi possible consequence
- Useful for documenting remission only
- Owners can monitor but should not adjust dose on the basis of results
What should an owner expect to see and do if their animal becomes hypoglycaemic?
Signs:
- Hunger
- food seeking
- altered judgement
- ataxia
- weakness
- collapse
- convulsions
What an owner can do in emergency/collapse:
Give dextrose absorbed across gums
At clinic
IV glucose or
Glucagon injection if not debilitated
What may be causing difficulty in controling DM with fluctuating requirements of insulin treatment?
Insulin
- related to bottle/batch
- dilution
Prolonged Somogyi
Inconsistent
- administration
- absorption
- diet
- exercise
Dramatic dose changes
Impatience with dose
Unstable illness
- Sepsis, inflammation
- Cirrhosis
- HAC treatment
Spontaneous remission or “honeymoon”
What may be causing difficulty in controling DM with persistently high requirements of insulin treatment?
Insulin
- species
- short activity
Diet
Diabetogenic therapy
Hyperadrenocorticism
Hypothyroidism
Hyperthyroidism
Acromegaly
Azotaemia
Progesterone
- metoestrus
Obesity
Phaeochromocytoma
Glucagonoma
What are future treatments for DM?
- Gene therapy
- Islet cell transplant (http://www.likarda.com/products/animal-health/) possible in the future
Summarise DM in the canine?
Presentation
- Middle aged dogs especially
- PU/PD, polyphagia, weight loss
Pathophysiology
- Metabolic consequence of reduced insulin
- Osmotic effects of glucose
Diagnosis
- Hyperglycaemia and glucosuria
Treatment
- Insulin (injection - usually BID)
- Consistent diet, consistent exercise
Monitor
- Owner diary, fructosamine +/- BGC’s
Your practice has bene treating Chloe a 7yr FN Cairn Terrier for diabetes for the last 10 months. The dog has been doing well and the owner is very pleased with how well Chloe has been doing since starting treatment.
She makes and appointment to see you because Chloe has been drinking more for the last 3 days despite no recent changes in insulin dose, diet or exercise. She brings a urine sample with her.
The Multistix® dipstick results include: glucose 4+, protein 2+, white blood cells, and erythrocytes
What maybe happening?
A urinary tract infection is likely. This could cause decreased insulin sensitivity
Task 2: Your practice has bene treating Chloe a 7yr FN Cairn Terrier for diabetes for the last 10 months. The dog has been doing well and the owner is very pleased with how well Chloe has been doing since starting treatment.
She makes and appointment to see you because Chloe has been drinking more for the last 3 days despite no recent changes in insulin dose, diet or exercise. She brings a urine sample with her.
The Multistix® dipstick results include: glucose 4+, protein 2+, white blood cells, and erythrocytes
What maybe happening?
A urinary tract infection is likely. This could cause decreased insulin sensitivity
What would you recommend?
Treatment for UTI and preferable urine culture and sensitivity
Your practice has bene treating Chloe a 7yr FN Cairn Terrier for diabetes for the last 10 months. The dog has been doing well and the owner is very pleased with how well Chloe has been doing since starting treatment.
The owner calls to tell you that Chloe was bin-raiding yesterday and now has vomiting and diarrhoea.
What telephone advice would you offer?
Would you advice that Chloe continues to receive insulin is she is vomiting or not eating, why?
What telephone advice would you offer?
Standard therapy for vomiting and diarrhoea which could include fasting
Would you advice that Chloe continues to receive insulin is she is vomiting or not eating, why?
Yes insulin should be given at 50% dose, insufficient to cause hypoglycaemia but enough to keep ketogenesis suppressed. A starved diabetic without insulin will switch on ketogenesis.
Your practice has bene treating Chloe a 7yr FN Cairn Terrier for diabetes for the last 10 months. The dog has been doing well and the owner is very pleased with how well Chloe has been doing since starting treatment.
She makes and appointment to see you because Chloe has been drinking more for the last 3 days despite no recent changes in insulin dose, diet or exercise. She brings a urine sample with her.
The Multistix® dipstick results include: glucose 4+, protein 2+, white blood cells, and erythrocytes
What maybe happening?
A urinary tract infection is likely. This could cause decreased insulin sensitivity
What would you recommend
Treatment for UTI and preferable urine culture and sensitivity
Six-months later following successful treatment of Chloe after your last visit. The owner calls to tell you that Chloe was bin-raiding yesterday and now has vomiting and diarrhoea.
What telephone advice would you offer
Standard therapy for vomiting and diarrhoea which could include fasting
Would you advice that Chloe continues to receive insulin is she is vomiting or not eating, why?
Yes insulin should be given at 50% dose, insufficient to cause hypoglycaemia but enough to keep ketogenesis suppressed. A starved diabetic without insulin will switch on ketogenesis.
Is there a more serious complication that you should be considering if initial therapy is not effective?
Diabetic dogs may get pancreatitis
If insulin doses are adjusted upwards in increments that are too large or to frequent, there is a risk of Somogyi effect.
What is it and what is the endocrine response?
It is insulin induced hyperglycaemia. The endocrine repose includes cortisol, adrenaline and glucagon to stimulate gluconeogenesis and induce insulin insensitivity
It can last 24-48 hours
Blood glucose curves are used in the management of canine diabetes mellitus to assess the response to insulin therapy. This procedure is more commonly used in dogs than cats because results are less likely to be confounded by stress hyperglycemia. Dogs generally remain calmer when they are kept in the hospital, whereas cats often become stressed.
The indications for performing a blood glucose curve are:
- The patient has just been started on insulin therapy – a blood glucose curve is performed 5 to 7 days after treatment is initiated.
- The insulin dose or formulation has been changed.
- A previously stable patient has developed clinical signs consistent with unregulated diabetes (e.g. PU/PD).
One of the key concepts in the management of diabetes mellitus is that individual animals respond differently to exogenous insulin, so the response to therapy must be assessed in each patient.
The specific procedure for performing a blood glucose curve is as follows:
- The first blood sample is collected before insulin is administered
- A blood sample is then collected every 2 hours for 12 to 24 hours
- If the dog receives insulin twice daily, 12 hours is sufficient.
- If insulin is given, 24 hours is ideal.
- Glucose concentrations obtained from the glucometer/laboratory are plotted with the concencentration on the y-axis and time on the x-axis.
When interpreting blood glucose curves, record 4 measures. What are these?
- Onset of insulin action relative to injection
- Duration of action
- Lowest glucose concentration attained (nadir concentration)
- Time of nadir (represents time of peak effect)
For the curve below, determine the values for the 4 measures described above. Insulin was injected at 0800, just after the first blood sample was drawn. This patient is receiving insulin twice daily at 0800 and 2000.
Onset of insulin = 2h
Duration of action = 10h
Lowest glucose concentration = 6.4 mmol/L
Time of nadir (peak effect) = 4h (at noon)
Many diabetic dogs will have blood glucose concentrations that rise above the renal glucose threshold at certain times of the day. However, it is the duration of hyperglycemia (and therefore glucosuria) that becomes important. Draw a line of the graph to indicate the approximate value for the renal threshold and estimate the number of hours that the dog will experience glucosuria each day. Some glucosuria can be tolerated (i.e. PU/PD does not develop; subclinical), but this is a key component of diabetes management and should be minimised.
Draw line at 10 mmol/L
Draw a schematic for making decision about DM treatment based on BGC?
Using the guidelines provided below, please interpret the following curves and provide recommendations.
Curve 1: Dog receives 0.25 IU/kg lente insulin (Caninsulin®) at 0800 and 2000.
Interpretation: Insulin is effective and the duration of action is adequate, yet there is inadequate control of hyperglycemia
Recommended action: Increase dose by 20% (from 0.25 IU/kg to 0.30 IU/kg) and recheck in 7 days. Remember that most dogs require dosages of 0.8 to 1.2 IU/kg once or twice daily.
Using the guidelines provided below, please interpret the following curves and provide recommendations.
Curve 2: Dog receives 0.8 IU/kg lente insulin (Caninsulin®) once daily at 0800.
Interpretation: Insulin is effective, but the duration of action is too short. Although the curve was stopped at 10PM, there was no further insulin action.
Recommended action: Switch to twice daily insulin injections. Lower dose by 20%, give every 12h, and recheck in 7 days.
Using the guidelines provided below, please interpret the following curves and provide recommendations.
Curve 3: Dog receives 2.5 IU/kg lente insulin (Caninsulin®) once daily at 0800.
Interpretation: This dog is demonstrating the Somogyi effect (also called ‘overswing’) where the insulin dosage is too high and the blood glucose concentrations are being lowered too far. Mechanisms to protect the dog against hypoglycaemia are then activated, including release of glucagon, cortisol, and epinephrine. These hormones induce hyperglycemia, which then resolves slowly over the next few hours.
Recommended action: Reduce the dosage by 75% or return to starting dosages for canine diabetes mellitus (0.25 to 0.50 IU/kg q12h). Recheck after 7 days.
