Canine diabetes mellitus Flashcards
Effects on insulin on carbs
*Most cells - receptor mediated glucose uptake via GLUT
*Liver
– enhances uptake, phosphorylation, glycolysis
– enhances glycogen storage
– inhibits glycogenolysis
Effects on insulin on fat
*Excess glucose ->pyruvate->AcoA and FFA
*Insulin:
– Activates lipoprotein lipase
– Inhibits hormone sensitive lipase
Effects on insulin on protein
*Increased protein anabolism / synthesis
*Inhibits gluconeogenesis
Insulin action
- inhibits ketogenesis
- stimulates glucose uptake
- stimulates K+ uptake
Diabetes mellitus Type 1 classification
- beta–cell destruction, usually leading to absolute insulin deficiency
- Immune-mediated (including LADA)
- Idiopathic
i.e. insulin-deficient
Diabetes mellitus Type 2 classification
- may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance
i.e. insulin resistant
Other specific types/causes of diabetes mellitus
- Diseases of the exocrine pancreas
- Endocrinopathies
– Cushing’s syndrome, Acromegaly,
– Phaeochromocytoma, Glucagonoma, Hyperthyroidism, - Genetic defects, Drug– or chemical–induced, Infections
Source of the problem for type 1 DM
Insulin production, due to:
* Pancreatectomy
* Pancreatitis
* Auto-immunity
* Islet cell hypoplasia
* Chemical toxicity
Source of the problem for type 2 DM
Affected insulin target, due to:
* Progesterone/agen
* Growth hormone
* Glucocorticoids
* Glucagon
* Catecholamines
* Thyroid
* Obesity
Aetiology of canine diabetes mellitus - type 1/insulin-deficient
- 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) - beta loss due to EPI / pancreatitis (probably common)
- Congenital beta loss (rare)
Aetiology of canine diabetes mellitus - type 2/insulin-resistant
- Progesterone (e.g. metoestrus) - an acromegaly (common)
- Hyperadrenocorticism, exogenous corticosteroids
- IGF-1/GH excess (pituitary acromegaly extremely rare)
What are almost all diabetic dogs? What are some exceptions to this?
Almost all diabetic dogs are insulin dependent (aka type 1)
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
Clinical presentation/signalment
- 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
Breed predispositions
- 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 (under)
- GSD (under)
Clinical presentation
- Polyphagia but losing weight
- Polydipsia and polyuria
- 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”
Pathophysiology
- Polyuria, polydipsia
– Osmotic diuresis - Polyphagia
– Insulin in CNS – hypothalamic satiety centre - Weight loss/exercise intolerance/lethargy
– NEB
– Reduced glucose and AA uptake - Recurrent infection (esp. UTI, conjunctivitis)
– Immunological compromise
– Local conditions favour microbial growth - Ketotic breath
– Ketogenesis - Cataracts
– Osmotic effects
Occasionally what are the first signs of illness?
- acute when the dog develops diabetic ketoacidosis (DKA)
- Dull, depressed, weak, possibly comatose
- Often vomiting
- Dehydrated
- IV fluids and critical care
Does ketonuria/ketotic breath = diabetic ketoacidosis?
- not always
- if eating and drinking: still straightforward management
Investigation
Urinalysis standard part of PU/PD work-up
* Glucosuria
* Glucosuria without hyperglycaemia is not DM
Other lab findings:
* increased ALKP/ALT
* increased cholesterol, triglycerides
* Fasting hyperglycaemia
* +/- hyponatraemia
* +/- ketonuria, ketonaemia
* Fructosamine
* Urine culture
Diagnosis
- Hyperglycaemia
– fasting hyperglycaemia
– >12mmol/l usually
– >5.5 – 12mmol/l more challenging - Glucosuria
– Renal threshold ~ 10-12mmol/L - +/- Ketonuria
- Fructosamine
– > 400µmol/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
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
When used to monitor blood glucose/diabetes management:
* Aiming for approx 400 - 450 nmol/l – excellent
* “normal” fructosamine suggests significant periods of hypoglycaemia
Tx for the collapsed, v+, not eating diabetic
- Fluid therapy
- soluble insulin
- +/- ICU
- see ketoacidosis set
Tx for the PUPD, ± ketonuria, eating and drinking diabetic
- Routine management
- intermediate insulin
Aims of treatment
- Prevent life threatening ketoacidosis
- Abolish clinical signs
- Restore lost condition/weight
- Reduceriskofcomplications
Tx considerations
- 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
2 licensed insulin products 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
ProZinc, Boehringer
* Protamine Zinc Insulin
* BID Cats, SID dogs
- Most patients require between 0.8 – 1.2 iu/kg/dose to stabilise
- 40IU/ml – must use companion syringes with vial product
Insulin handling/storage
- Insulin 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
Diet
- essential to stick to good quality, consistent diet
- usually feed 2x daily with BID dosing
- feed 2x daily with SID dosing
- dry/tinned commercial foods
- Calculate the patients energy requirements and ensure being fed correct amount
– [(30 x BW) + 70] x illness factor = MER (kcal) - food should be high in complex carbs to minimise post-prandial glucose peaks
- food should be high in fibre
- avoid semi-moist foods
- if possible, O should be encouraged to feed 1 of the ‘glucomodulation’ diets
– chappie also seem effective
Body condition management
- If the dog is thin, then the daily calorie intake must be increased accordingly
- If the dog is overweight, then careful and monitored weight reduction will be helpful
Life style management
Diabetic patients need consistent regular exercise at a similar time each day
* Owners must understand and be willing to comply
* Owners can learn to adapt food volume for particularly active days
How to start tx
- 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
Blood glucose curves - what does it do in terms of monitoring?
- Tells you what effect the insulin is actually having
Can BGC be done at home?
- yes if stressed
Aims of BGC
- Is insulin working at this dose?
- What is nadir?
- When is nadir?
- What is duration of action for the insulin?
- Somogyi happening?
Disadvantage of BGC
- Inconsistent curves despite consistent management (25-33% opposite management suggested in duplicate curves)
What is somogyi?
- rebounding high blood sugar that is a response to low blood sugar
what is nadir?
= the lowest point on a blood glucose curve
- often considered the same as the peak of insulin activity
Glycated haemoglobin (GHb) - what is it? what is its use?
- 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 for monitoring diabetes management
- 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
Complications of diabetes management/tx
- Hypoglycaemia
- need to warm O
- clinically uncommon
- fatal rarely
- hunger, food seeking, altered judgement, ataxia, weakness, collapse, convulsions
- dextrose absorbed across gums (O can do in emergency/collapse)
- IV glucose at clonic or glucagon injection if not debilitated
