Canine diabetes mellitus Flashcards
(40 cards)
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
