Feline diabetes mellitus Flashcards
Signalment
- Cats >7 years of age are at greatest risk
- M and MN cats > F and FN
- Breeds:
– Burmese cats have a higher risk in the UK and in Australia, NZ and Europe * think about other breeds such as Tonkinese, Norwegian Forest - Obesity: can increase risk of diabetes up to 4 x compared with optimal weight cats
- Indoor and inactive cats
- Cats on treatments such as:
– glucocorticoids
– progestagens
Clinical Signs - typical CS
- polyuria
– the renal threshold for glucose is ~14-16 mmol/l - polydipsia
- weight loss, but the cat might still be obese initially
- lethargy
- polyphagia
Clinical Signs - less common
- weakness
- plantigrade stance
- depression/anorexia
– suggests DKA - muscle loss
Which cats is pre-diabetes / subclinical diabetes common in?
- obese cats
Physical exam findings in diabetic cats
- Variable BCS: poor, obese
- Poor hair coat
- Dehydration?
- Abdominal pain if concurrent pancreatitis
- Evidence of peripheral neuropathy?
- Breath smelling of ketones?
What causes type I diabetes in cats?
- a deficiency of insulin
– pancreatic β cell loss - destruction of cells
– chronic pancreatitis, +/- EPI
-> inflammatory mediators may contribute to insulin resistance ie Type I→Type II
– pancreatic amyloidosis
– glucose toxicity
– immune mediated disease - congenital lack of β cells
– very rare in cats
What causes type II diabetes in cats?
- an inability to respond to insulin
– cats often still have functioning beta cells at the time of diagnosis - (+/- relative insulin deficiency)
Glucose toxicity
- hyperglycaemia -> amylin deposition in islets -> beta cell apoptosis -> permanent IDDM
- beta cell apoptosis -> hyperglycaemia
How can pancreatitis/obesity/glucocorticoids/megoestrol acetate/infecyion cause glucose toxicity & how can they be resolved?
- Carbohydrate intolerance → hyperglycaemia ->
- Glucose toxicity inhibits beta cell insulin production ->
- Induction of apparent IDDM ->
- Hyperglycaemia controlled or cause of peripheral insulin resistance resolves ->
- Glucose toxicity resolves, beta cells resume insulin production ->
- Diabetic Remission: Hypoglycaemia develops, Ability to maintain normoglycaemia is restored
Consequences of insulin deficiency/resistance
- Persistent hyperglycaemia and glucosuria
- Fat mobilisation is favoured leading to
- hepatic lipidosis
- hepatomegaly
- hypercholesterolaemia
- hypertryglyceridaemia
- increased catabolism
Failure to intervene→ketonaemia, ketonuria→DKA
Why must pts have type I diabetes to have ketotic breath?
- it only takes a small amount of insulin for ketone production to be shut down
- if ketotic = no insulin made, so must be a production problem
Is type I or II more common in cats?
- type II
Diagnosis - things to document
- persistent hyperglycaemia and glucosuria
- AND appropriate clinical signs
Diagnosis - things to rule out
- stress hyperglycaemia and glucosuria
- usually BG is < 16mmol/l, but not always
- usually resolves within a few hours, but not always
Diagnosis - considering concurrent dz, esp if CS not typical
- could the cat have pancreatitis or even “triaditis”
– abdominal ultrasound
– blood tests including fPLI - could your cat be hyperthyroid?
– is there any overlap in clinical signs between hyperT4 and DM? What are the main differences?
Diagnosis: Urinalysis
USG:
* affected by glucosuria in some situations
* not always quite as low as you think it will be for a polyuric cat
Dipstick:
* confirms glucosuria
* rules out ketonuria
* any changes that suggest UTI?
Sediment analysis
* often no active sediment even if there is a UTI
Culture and sensitivity
Glucosuria differentials
Common
* DM
* Stress hyperglycaemia
Rare
* Renal tubular disease
* Fanconi syndrome
* Primary renal glucosuria
* Nephrotoxin exposure
Fructosamine
- Indicates the average BG during the preceding 1-3 weeks
- Often not affected by transient stress hyperglycaemia
- Might be normal in recent or mild diabetics
– repeat if persistent glucosuria at home?
– if you think the cat has DM don’t rule it out too quickly: cats become diabetic over a period of time so there can be some waxing and waning of clinical signs - Might be affected by hypoglycaemia induced periods of hyperglycaemia (the Somogyi effect) if they are prolonged
– less useful for monitoring diabetic cats on treatment than for initial diagnosis
– fructosamine might be high even though the cat has had episodes of hypoglycaemia
Problems with relying on fructosamine
Fructosamine concentrations are variable depending on:
* individual cats
* different labs and methodology
* age
* gender
* serum protein concentrations
* hydration status
* thyroid status and conditions that modify protein turnover, eg fructosamine tends to be lower in hyperthyroid cats
Diagnostic plans: what else you need to consider
causes
* pancreatitis
* acromegaly
consequences
* UTI
* peripheral neuropathy
contributing factors
* obesity
concurrent disease
* airway disease? +/- treatment
* inflammatory disease (dental disease)
What are the aims of treating diabetes in cats?
- Resolve or at least reduce clinical signs
– maintain or improve QOL - Select a treatment protocol suited to the owners and their cat
- Minimise risk of complications
– hypoglycaemia
-> diabetic remission can occur
-> insulin induced hypoglycaemia
– DKA - Optimise body weight
- Increase exercise
Weight loss as a treatment for diabetes in obese cats - what can it lead to? what do we need to be aware of in cats re rapid weight loss? how to do it?
- Can lead to diabetic remission
– temporary
– permanent? - Rapid weight loss in cats is not a good idea (hepatic lipidosis)
– aim for 2% weight loss/month - Wet food
– tends to reduce calorie intake
– helps maintain hydration - Diabetic cats can continue grazing rather than having strict timed feeds but ensure not > daily food allowance
- Consider environmental enrichment to encourage activity
– feeding puzzles
The ideal diabetic diet for cats
- High protein
– normalises fat metabolism and provides a consistent energy source (gluconeogenesis)
– limits the risk of hepatic lipidosis during weight loss
– prevents loss of lean muscle mass - Restricted carbohydrate
– helps relieve tendency to hyperglycaemia and glucose toxicity - Wet formulation
– improves satiety - Results: higher diabetic remission rates and improved glycaemic control
- BUT if a cat is on a different therapeutic diet for a concurrent illness that diet should be continued. For example:
– continue a renal support diet for an older cat with CKD that becomes diabetic
– feed for IBD if you suspect the cat has triaditis
Insulin treatment in diabetic cats - licensed products
- Caninsulin
– “BG<20 mmol/l start on 1IU bid”
– “BG> 20 mmol/l start on 2 IU bid” - ProZinc
– “o.2-0.4 IU/kg bid”
Insulin treatment in diabetic cats - unlicensed products (cascade)
- glargine
– rapid onset/long duration - determir
- most cats start on 1 IU bid
Insulin treatment in diabetic cats - syringes
- use the correct insulin syringe for the insulin being used
Insulin treatment in diabetic cats - dose changes
- Dose changes are usually 0.5 IU
- smaller changes aren’t feasible or accurate
- never dilute insulin
Insulin treatment in diabetic cats - dose increase
- Dose increase not more often than every 7 days
- rapid increase in dose increases risk of hypoglycaemia→rebound hyperglycaemia
Starting insulin treatment: Day 1
- Morning: check BG, feed and give insulin dose
- is there an ideal time to feed?
- Check BG every 2-4 hours
– assess response to insulin
– monitor for hypoglycaemia
– try to establish the nadir
-> might take 10-12 hrs or more - Review dose based on BG results
– nadir <4.5mmol/l→↓ dose by 0.5IU
What next?
* Send your patient home
– it can take at least 3 days to equilibrate to any dose change
* Review after 5-14 days
* Discharge with detailed
written information/instructions as well as a discharge appointment
– provide a point of contact at the practice
The ideal BG curve
- BG < 14 mmol/l throughout
– limits osmotic diuresis
– ↓ risk of glucose toxicity - Nadir between 4.5-8 mmol/l
- Time of nadir ideally between 6-10 hours
- Duration of action ~ 12 hours
What is important if aiming for remission?
- rapid/early tx
- glucose toxicity: high BG → glycogen deposition in the pancreas→ apoptosis of beta cells
- breaking the cycle might prevent irreversible DM
Is timing of diabetic remission predictable?
- no
- warn owners about possibility of hypoglycaemia
Indicators of diabetic remission
- hypoglycaemia despite low dose insulin
- no glucosuria
- “too good to be true”
What to do after diabetic remission
- continue dietary management
- monitor closely
– relapse is quite common → IDDM - Non-absorbing litter (hydrophobic sand)
- Litter in plastic bags
- In-litter detection systems (now discontinued)
Are oral hypoglycaemic drugs useful in cats?
- Owners may ask about drugs that are used in Type II DM in people
Glipizide:
* has evidence to support beneficial effects (? in 40% cats?)
* promotes insulin secretion from the pancreas
* adverse effects can include
– cholestasis
– hypoglycaemia
– vomiting
* might contribute to progression of DM and pancreatic amyloidosis
* seldom used
New addition to oral hypoglycaemics
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors
- Velagliflozin - Senvelgo - Boehringer Ingelheim EU/UK
- Bexagliflozin - Bexacat – Elanco USA
– Promotes renal losses of glucose
– Depends on reversible glucotoxicity as underlying pathogenesis
– Can’t use as sole therapy in IDDM
– May use as adjunctive and in NIDDM (monitor ketones)
– Not all cats Type II and not all Type II reversible
– eDKA risk within first week – more complicated to manage than DKA
– May increase polyuria initially- osmotic diuresis
– Polyuria may resolve if assists sufficiently with reversible gluco-toxicity to restore sufficient islet function.
Human vs feline DM
- Strict glycaemic control is not as essential in cats as in people
– long term complications in people are a major concern
-> cats don’t have similar issues - We know that people with DM feel less well if they have low normal BG than if they have a slightly high BG
Monitor the clinical signs
- General demeanour
- Water intake
- Appetite
- Weight/BCS
- Owner’s diabetic diary
– off days?
– check compliance
– time of insulin injections - Careful evaluation of clinical history and physical exam can be more useful than a BG curve
- BG curves are for unstable not stable patients
– significant day to day variability
– situation at home won’t be the same as in the practice
-> stress
-> variable food intake and exercise
– a BG curve day (even at home) is not a “normal” day for a diabetic cat
Urinalysis for monitoring
- Most diabetic cats will have glucosuria
- Persistent absence of glucose in urine could mean risk of hypoglycaemia
– insulin overdose?
– diabetic remission? - Ketonuria can indicate DKA
- Blood or change in pH can indicate UTI
Diabetic monitoring: can we use fructosamine?
- Trends are more useful than individual results
– variability in lab results esp in-house
– doesn’t give indication of degree of hypo or hyperglycaemia - Beware of relying on the reference range to compare results
– fructosamine > reference range
-> even a well controlled diabetic will have periods of hyperglycaemia each day
-> may not need a change in dose - fructosamine in reference range
-> could indicate periods of hypoglycaemia even if owner unaware
-> may need dose reduction - Less useful in monitoring than in diagnosis
- Always interpret fructosamine in light of the clinical signs
When should we use blood glucose curves?
- To detect hypoglycaemia
– more helpful in decisions about reducing insulin dose than increasing
– may need to do hourly BG rather than every 2-3 hours - If BG is consistently high there is likely no point in continuing that curve for the full 12 hours
The Freestyle Libre
- Starter pack comes with the reader and 2 sensors
- The sensors last up to 14 days each
- No need for calibration
- Sensor is water resistant
- Smartphone App to enable glucose readings to be downloaded and analysed
- £160 for the starter pack
The future?
What are the likely causes of unstable diabetes in cats?
- Compliance issues
– is the owner giving the right dose of the right insulin at the right time?
– is only ONE owner doing this?
– how do the owners record what they are doing - UTI
– often without clinical signs of lower urinary tract disease - Pancreatitis
– common comorbidity in cats and not always easy to manage - Significant dental disease
Is insulin more common in cats than dogs?
- cats
Diabetogenic hormones
- glucocorticoids (iatrogenic more likely than Cushing’s disease in cats)
- growth hormone (acromegaly)
– 95% of acromegalic diabetic cats have insulin resistant DM
– up to 25% of cats with DM might have acromegaly? (but don’t know what population of cats this data came from) - progestogens
- adipokines/cytokines
- adrenaline/noradrenaline * glucagon
Diabetogenic scenarios
- inflammatory conditions
What is insulin resistance?
- no response to insulin at a dose of >2.2IU/kg/dose
General approach to suspected insulin resistance
- Review the history for clues
– poor compliance?
– any GI signs? - Thorough physical exam
– dental status?
– abdominal pain?
– any mass lesions? - Blood tests:
– Haematology
-> markers of inflammation/infection?
-> anaemia suggesting comorbidity?
– Biochemistry
-> any evidence of other organ involvement? - fPLI
- Urinalysis
– stix
– sediment
– culture
– (SG less useful in diabetic cats) - Diagnostic imaging
– abdominal ultrasound?
-> check liver/GI tract/pancreas - Blood test for IGF1
– could the cat be acromegalic?
Cycle of insulin resistance
Insulin Resistance -> Increased demand on insulin secretion -> beta−cell exhaustion -> Failure of glycaemic control -> Uncontrolled hyperglycaemia -> Insulin Resistance -> …
Hypoglycaemia in cats
- BG < 3-3.5mmol/l
- Mild hypoglycaemia is well tolerated and easily missed by owners
- Severe hypoglycaemia is life threatening
- Detection of hypoglycaemia or a strong clinical suspicion of hypoglycaemia are the only reasons why an insulin dose might be changed more often than every 5-7 days
– ie we may reduce a dose but never increase a dose in this time
Hypoglycaemia - CS to look out for (i.e. for O)
- lethargy
- muscle tremors
- anorexia and vomiting
- ataxia
- recumbency
- vocalisation
- seizures
Hypoglycaemia - action at home
- apply honey or glucose to oral mucous membranes
– advise to keep a dextrose gel available - feed a proper meal ASAP
Hypoglycaemia - action in clinic
- 25% dextrose solution
– 2-4 mls slow iv over 5-10 minutes - continue with a 5% dextrose CRI
- monitor clinical signs and BG
Review treatment for diabetes
When should an owner contact the vet/nurse?
Seek urgent advice if
* any signs suggesting hypoglycaemia
* anorexia
* vomiting
* lethargy/weak
But also need to seek advice if
* weight loss
* polydipsia
* polyphagia
* plantigrade stance developing
Myths about diabetes in cats - anti-insulin antibodies
- in the past thought to be a cause of insulin resistance but no evidence to support this even though we are injecting “foreign proteins”
Myths about diabetes in cats - discarding open bottles after 4-6w (even if in date)
- this might not be necessary if insulin is stored in the fridge, handled carefully and doesn’t become discoloured or flocculant
Myths about diabetes in cats - timing is crucial and never miss a dose
- be kind to owners and allow them to give injections every 12 +/- 2 hours
- missing the occasional injection completely is unlikely to be a problem
Myths about diabetes in cats - stabilisation is quick, and afterwards just needs to be maintained
- management of diabetic cats with insulin is an ongoing challenge
- changes should always be done slowly and with time for the patient to adapt
Possible new treatment
- Extended-release glucaogon-like peptide-1 [GLP-1] analogs such as exenatide
- Secreted from the GI tract in response to ingestion of nutrients
- enhances insulin secretion
- decreases glucagon secretion
- induces satiation
- slows gastric emptying
