PATHOLOGY - Diabetes Mellitus Flashcards
What is the pathophysiology for diabetes mellitus in dogs?
In dogs, there is immune-mediated destruction of the islets of Langerhans, resulting in decreased insulin production
Which risk factors can progress diabetes mellitus in dogs?
Pancreatitis
Progesterone
Obesity
Cortisol
Inflammation
Progesterone, obesity, cortisol and inflammation all cause insulin resistance
What is the pathophysiology of diabetes mellitus in cats?
In cats, insulin secretion is inadequte due to a combination of islets of Langerhans pathology and peripheral insulin resistance. The most common form of pathology at the islets of Langerhans in cats in amyloidosis which results in insensitivity of the islet cels to changes in blood glucose concentrations
Which factors can cause cats to develop peripheral resistance to insulin?
Obesity
Growth hormone
Progesterone
Cortisol
Glucose toxicity
What is glucose toxicity?
Glucose toxicity is where there are very high blood glucose concentrations resulting in the inhibition of insulin receptors
How can glucose toxicity be resolved?
Glucose toxicity can be resolved if the blood glucose levels are reduced for several weeks, which can allow the insulin receptors to regenerate
What is the typical signalement for diabetes mellitus?
Older animals
Intact females
Breed predispositions
Why are intact female animals at an increased risk of diabetes mellitus?
Intact females are at an increased risk of diabetes mellitus due to progesterone mediated insulin resistance. If intact female dogs present with diabetes you should spay them as a surgical emergency
Which dog breeds are predisposed to developing diabetes mellitus?
Samoyeds
Terriers
Which cat breeds are predisposed to developing diabetes mellitus?
Bermese cats
What are the general clinical signs of diabetes mellitus?
Usually BAR
PUPD
Polyphagia
Anorexia (in cats)
Weight loss
Lethargy
Blindness (in dogs)
Hindlimb weakness (in cats)
What causes blindness in dogs with diabetes mellitus?
Diabetic cataracts
What causes hindlimb weakness in cats with diabetes mellitus?
Diabetic neuropathies result in hindlimb weakbness and a hindlimb plantigrade stance
Which diagnostic tests can be done to confirm a diagnosis of diabetes mellitis?
Urinalysis (urine dipstick)
Biochemistry
What is a key indicator of diabetes mellitus on a urine dipstick?
Glucosuira
Ketones (not always)
What is a key indicator of diabetes mellitus on biochemistry?
Hyperglycaemia above the renal threshold
What is the renal threshold of glucose?
The renal threshold for glucose is the blood glucose concentration where the kidney’s ability to reabsorb glucose from the renal tubules is exceeded. Once the serum glucose levels rise above this threshold, the kidneys begin to excrete glucose into the urine
What is the renal threshold of glucose in dogs?
10mmol/L
What is the renal threshold of glucose in cats?
12mmol/L
Which other biochemistry findings are common with diabetes mellitus?
Increased liver enzymes
Hypercholesterolaemia
Why can the liver enzymes be increased with diabetes mellitus?
Liver enzymes can be increased due to steroid induced hepatopathies however there should be no signs of liver dysfunction
What should you be aware of when assessing hyperglycaemia in cats?
Cats can have a marked stress induced hyperglycaemia that goes beyond the renal threshold so it is important to differentiate between a true diabetes mellitus and physiological stress
What can be used to differentiate between a true diabetes mellitus and physiological stress induced hyperglycaemia?
Serum fructosamine levels
What is fructosamine?
When glucose circulates in the blood, it can bind to serum proteins, and fructosamine is formed when glucose specifically binds to albumin. When fructosamine levels are beyond the reference range, this indicates a more chronic hyperglycaemia which indicates a true diabetes mellitus rather than a physiological stress hyperglycaemia
What is the definition of diabetic stability in veterinary medicine?
In veterinary medicine, diabetic stability refers to the management of the clinical signs associated with diabetes mellitus
How do you manage diabetes mellitus in dogs?
Insulin injections
Why are insulin injections the only option for management of diabetes mellitus in dogs?
Insulin injections are the only treatment option for diabetes mellitus in dogs as diabetes is caused by an autoimmune response which results in no insulin being produced
How do you manage diabetes mellitus in cats?
SGLT 2 inhibitors
Insulin injections
How are SGLT 2 inhibitors used to manage diabetes mellitus in cats?
SGLT 2 inhibitors inhibit the SGLT 2 co-transporter which is responsible for reabsorping glucose from the urine into the blood at the proximal convoluted tubule, resulting in a decreased reabsorption of glucose
What prevents patients going into hypoglycaemia when on SGLT 2 inhibitors?
The SGLT 1 co-transporters are still functional and thus prevent patients from going into hypoglycaemia
How can SGLT 2 inhibitors put diabetic cats into remission?
SGLT 2 inhibitors will increase the renal excretion of glucose and decrease the blood glucose levels enough to correct glucose toxicity which can allow the insulin receptors to begin to regenerate which could eventually put the cat into remission
Give an example of an SGLT 2 inhibitor
Velagliflozin
How should you approach administration of velagliflozin in cats?
Administer velagliflozin once daily and feel the cat twice daily. Wait seven days and adjust the dose of velagliflozin if necessary. Repeat this until the patient is stable
How should you monitor patients that are being treated with SGLT 2 inhibitors?
- Owners should monitor for ketones in the urine using a urine dipstick every 1 - 3 days
- At 1 week, do a full clinical exam, measure body weight and assess blood ketone levels
- At 4 weeks, do a full clinical exam, measure body weight, assess blood ketone levels, urinalysis and assess blood frustosamine levels
- Re-assess all of these factors every 3 months after that
What are some of the potential side effects of SGLT 2 inhibitors?
Acute diarrhoea
Lower urinary tract infections (UTI)
Weight loss
PUPD
Mild dehydration
Hypersalivation
(T/F) Acute diarrhoea is a rare side effect of SGLT 2 inhibitors
FALSE. Acute diarrhoea is a very common side effect of SGLT 2 inhibitors however it should be short-lasting and self-limiting
Why are patients on SGLT 2 inhibitors at an increased risk of lower urinary tract infections?
Patients being treating with SGLT 2 inhibitors are at an increased risk of lower urinary tract infections due to the increased glucose content in the urine which promotes bacterial colonisation
Which criteria would make a cat inappropriate for SGLT 2 inhibitors?
Previous diabetic ketoacidosis
Lethargy, anorexia and/dehydration on clinical exam
Evidence of liver disease
Evidence of significant kidney disease
Blood ketones above 2.5mmol/L
Positive ketones on a urine dipstick
These cats require insulin injections , NOT SGLT 2 inhibitors
What are the three main sources of insulin in veterinary medicine?
Bovine insulin
Porcine insulin
Recombinant human insulin
Which source of insulin is most similar to feline insulin?
Bovine insulin is most similar to feline insulin
Which source of insulin is most similar to canine insulin?
Porcine insulin is most similar to canine insulin
What are the two different concentrations of insulin available in veterinary medicine?
40 iu/ml
100 iu/ml
Make sure to not get mixed up between the syringes as you risk over- or under-dosing your patient
What are the four different types of insulin available in veterinary medicine?
Soluble insulin
Isophane insulin
Lente insulin
PZI insulin
What should you make owners aware of when you begin treating their pet with insulin injections?
You need to make owners aware that insulin injections do not work in the same was as normal insulin. Thus it is very important to carefully manage diet and exercise and to maintian the patient’s health for the insulin injections to work
What blood glucose levels are you aiming for for a diabetic patient to be stabilised?
You are aiming for mild hyperglycaemia just above the renal threshold and management of clinical signs for a patient to be classified as a stable diabetic
Outline a method that can be used to stabilise a diabetic dog with insulin injections
- Give a starting dose between 0.3 - 0.5 iu/kg of lente insulin every 12 hours, and feed the patient twice a day
- Wait for three days and then adjust the insulin dose based on the average morning urine glucose measurements over five days
- If there is no glucose in the urine, decrease the insulin dose by 5%, if there is mild glucose in the urine, maintain the insulin dose, if there is too much glucose in the urine, increase the insulin dose by 5%
- Repeat this process until the patient is stabilised or you reach over 2 iu/kg of insulin
What is indicated if the patient is still not stable with insulin doses over 2 iu/kg?
If the diabetes patient is not stable with insulin doses over 2iu/kg, this indicates there is insulin resistance. Continue to increase the insulin dose but also begin investigations for causes on insulin resistance
What are the limitations of using urine glucose measurements to assess a patient’s response to insulin injections?
Urine glucose levels do not correspond to blood glucose levels
Outline another method that can be used to stabilise a diabetic dog or cat with insulin injections
- Give a starting dose between 0.3 - 0.5 iu/kg of lente (or PZI in cats) insulin every 12 hours, and feed the patient twice a day
- Wait for three days and then adjust the insulin dose based on the blood glucose levels (train owners to use a glucometer)
- Repeat this process until the patient is stabilised or you reach over 2 iu/kg of insulin
Which factors should you have owners monitor and report back to you when treating a patient with insulin injections?
Have the owners keep home records on the urine glucose and ketone levels, urination, thirst, appetite, demeanous and any hypoglycaemic episodes
Which factors should you assess on clinical examination when monitoring patients being treated with insulin injections?
Check weight
Assess eyes
Assess for neuropathies
Which factors should you assess on biochemistry when monitoring patients being treated with insulin injections?
Blood glucose
Blood frustosamine
Don’t worry about doing this is owners have financial constraints
How do continuous glucose monitoring systems (CGMS) work?
Continuous glucose monitoring systems (CGMS) measure the glucose levels in the interstitial fluid
What are the benefits of assessing HBA1c levels in dogs with diabetes mellitus?
When glucose is circulating in the blood it can bind to haemoglobin and form HBA1c. Haemoglobin lasts longer in the bloodstream than albumin and thus is a better reflection of long term hyperglycaemia than fructosamine
Which aspects of the patient’s daily routine should be carefully planned to help manage diabetes mellitus?
Feeding times
Feeding amounts
Type of food
Insulin amount
Timing of insulin injection
Exercise
Environment
Which factors should you consider when feeding diabetic patients?
Palatability
Energy
Fat
Carbohydrates
Protein
Fibre
Which factors can affect the energy requirements for a diabetic patient?
Body weight
Activity levels
Breed
Age
Sex
Concurrent disease
Gastrointestinal function
Owner factors
How much of the daily energy requirement should you feed obese animals with diabetes mellitus?
Feed 70% of the calculated energy requirement for the target weight
How much of the daily energy requirement should you feed thin animals with diabetes mellitus?
Feed 100% of the calculated energy requirement for the optimal weight
Which carbohydrates should you avoid in patients with diabetes mellitus?
Simple sugars
What kind of diet should you feed dogs with diabetes mellitus?
Highly palatable
50-55% ME in complex carbohydrates
Less than 20% ME in fats
14-30% ME in protein
No simple sugars
ME stands for metabolisable energy
Why are complex carbohydrates beneficial for dogs with diabetes mellitus?
Complex carbohydrates such as starch and dietary fibre cause a delayed increase in blood glucose as starch is slowly digested and dietary fibre has a reservoir effect which gives the iatrogenic insulin time to work
What kind of diet should you feed cats with diabetes mellitus?
Highly palatable
50-55% ME in protein
No simple sugars
Restricted complex carbohydrates
Why should complex carbohydrates be restricted in cats with diabetes mellitus?
Carbohydrates have decreased glucokinase activity and thus have an inefficient carbohydrate metabolism, making glucose a weak stimulator of insulin in cats. Furthermore, dietary fibre decreases palatability in cats
What is a good stimulator of insulin release in cats?
Cats have a very efficient protein catabolism so arginine is a better stimulator of insulun secretion
What are the potential complications of diabetes mellitus?
Cataracts (in dogs)
Neuropathies (in cats)
Ketoacidosis
Hypoglycaemia
How should you approach management of a diabetic patient that has stopped eating?
- First distinguish if the patient is not eating but still systemically well or if the patient is not eating and systemcally unwell
- If the patient is systemically unwell and not eating, they should be brought into the clinic for monitoring
- If the patient is systemically well and not eating, try and determine why they are not eating. Ask the owner when they had their last meal, has the feed changed etc? Decrease the insulin dose by half and if the patient proceeds to eat then give them the other half of their insulin
What is the main risk of surgery on diabetic patients?
Hypoglycaemic collapse
How should you approach surgery in patients with diabetes mellitus?
- Ensure the diabetes is stable
- On the day of surgery (try to operate early in the morning), give half of the insulin dose as the patient will have been fasted leading up to surgery
- Monitor the blood glucose levels during surgery and if they fall below hyperglycaemia, begin a dextrose infusion
- Begin to feed the patient as soon as possible following surgery and continue to monitor their blood glucose levels
Which concurrent diseases can often present with diabetes mellitus?
Hyperadrenocorticism (Cushing’s disease)
Pancreatitis
Acromegaly
What is acromegaly?
Acromegaly is a condition where there is an excessive production of growth hormone
What are the potential causes of collapse in a diabetic patient?
Diabetic ketoacidosis (DKA)
Hypoglycaemia
Sepsis
Neuropathy (in cats)
Which factors contribute to the development of diabetic ketoacidosis (DKA)?
No insulin
Stress
Anorexia
What is the pathophysiology of diabetic ketoacidosis (DKA)?
When there is no insulin, glucose will remain in the bloodstream and cannot be utilised by the cells for ATP production. When this happens, the body will begin to metabolise lipids to produce energy causing non-esterified free fatty acids to be released into the bloodstream and oxidised by the liver into ketone bodies. Diabetic ketoacidosis is when ketone body production and metabolism becomes unregulated due to there being no insulin present to move glucose into the cells, and due to an increase in counter-regulatory hormones such as adrenaline, growth hormone and cortisol (released due to physiological stress) and glucagon (which is released to try and increase glucose levels). This results in excessive ketone body production and ketosis. Ketone bodies can cause metabolic acidosis and when they are renally excreted they cause osmotic diuresis and thus will also excrete water, electrolytes and buffer
What is the most commonly produced ketone body in small animals?
β-hydroxybutyrate
Why is diabetic ketoacidosis (DKA) more common in dogs?
Diabetic ketoacidosis (DKA) is more common in dogs as diabetic ketoacidosis occurs due to a complete absence of insulin, which is much more commonly seen in dogs due to their pathophysiology
What are the clinical signs of diabetic ketoacidosis (DKA)?
Dehydration
Shock (tachycardia, poor perfusion etc)
Haemorrhagic diarrhoea
Acidosis
Collapse
Death
How do you diagnose diabetic ketoacidosis (DKA)?
History and clinical signs
Clinical examination
Urine dipstick
Biochemistry
What would you typically find on a urine dipstick in a patient with diabetic ketoacidosis (DKA)?
Glucosuria
Ketonuria
What would you typically find on biochemistry in a patient with diabetic ketoacidosis (DKA)?
Hyperglycaemia
Hypokalaemia
Hypophosphataemia
Azotaemia
Increased liver enzymes
What are the causes of hypokalaemia in diabetic ketoacidosis (DKA)?
Anorexia decreases dietary potassium
DKA causes osmotic diuresis which causes increased renal excretion of potassium
Treatment with insulin causes potassium to move into the cells
How do you treat diabetic ketoacidosis (DKA)?
Intravenous fluid therapy
Insulin injections
Close monitoring
What are the aims of intravenous fluid therapy when treating diabetic ketoacidosis (DKA)?
Correct fluid deficits
Manage maintenance requirements
Manage ongoing losses
Treat shock if indicated
Supplement potassium
Supplement phosphorus
Which starting dose can you use for spiking fluids with potassium?
10 mmol of potassium chloride per 500ml of fluid
How can you treat hypophosphataemia in patients with diabetic ketoacidosis (DKA)?
Feeding the patient
Spike the fluids with potassium phosphate
Which type of insulin should you use when treating diabetic ketoacidosis (DKA)?
Soluble insulin as it has a rapid onset of action
What is the best route of administration for insulin in patients with diabetic ketoacidosis (DKA)?
Intramuscular injection (IM)
How should you approach administering IM insulin to patients with diabetic ketoacidosis (DKA)?
- Give an initial dose of 0.2 iu/kg of IM soluble insulin
- Give subsequent IM doses of 0.1 iu/kg of soluble insulin every 2-4 hours
- Monitor blood glucose levels carefully
- Start a dextrose infusion if the patients begins to become hypoglycaemia
How should you approach administering IV insulin to patients with diabetic ketoacidosis (DKA)?
- Give 0.03 units/kg/hr of IV soluble insulin, making sure to run 50ml of fluid before the insulin
- Monitor blood glucose levels carefully
- Start a dextrose infusion if the patients begins to become hypoglycaemia
Which parameters should you monitor carefully when treating patients with diabetic ketoacidosis (DKA)?
TPR
Urine
Perfusion parameters
PCV/TP
Serum glucose
Serum potassium
Serum phosphate
Why does treatment of diabetic ketoacidosis (DKA) differ in cats being treated with SGLT 2 inhibitors?
Treatment of diabetic ketoacidosis (DKA) differs in cats being treated with SGLT 2 inhibitors as the SGLT 2 inhibitors maintaining their blood glucose levels at a much more stable rate so there is a much higher risk of these patients going hypoglycaemic when you begin insulin treatment for the DKA
How do you treat diabetic ketoacidosis (DKA) differ in cats being treated with SGLT 2 inhibitors?
- Stop the SGLT 2 inhibitors
- Fluid therapy
- IM soluble insulin
- IV dextrose infusion
5 Monitor the blood glucose levels every hour for hypoglycaemia, aiming for levels between 5 - 12mmol/L - After 4 hours, reduce the monitoring to every other hour
- When the blood glucose levels begin to rise (can take 2 to 3 days) and the cat has started eating, beging PZI insulin
What are the potential complications of diabetic ketoacidosis (DKA)?
Lower urinary tract infections (UTIs)
Pancreatitis
Gastrointestinal haemorrhage
Sepsis
Acute renal failure
Disseminated intravascular coagulation (DIC)
Pulmonary thromboembolism
What are some of the causes of unstable diabetes mellitus and thus diabetic ketoacidosis?
Incorrect insulin administration
Incorrect insulin dose
Incorrect insulin type
Infection
Obesity
Hyperadrenocorticism
Pancreatitis
Acromegaly
What are some of the clinical signs of acromegaly?
Inspiratory stridor
Large extremities (head, limbs, gingiva)
Thickened skin
Hepatomegaly
Diabetes mellitus
Neurological signs
How do you diagnose acromegaly?
Increased blood IGF-1 levels
What are the main causes of hypoglycaemia in diabetic patients?
Acute insulin overdose
Chronic insulin overdose
What are the clinical signs of hypoglycaemia?
Polyphagia
Hyperaesthesia
Trembling
Ataxia
Seizures
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