exam 8 L. 9: DKA

Question 1

DKA

Answer 1

• Stable, uncomplicated canine
• stable, uncomplicated feline
• stable, ketotic
• diabetic ketoacidotic

Question 2

Stable uncomplicated canine

Answer 2

1) history: excessive drinking and urination, how is hungry but losing weight
2) physical exam:
- may be relatively normal
- cataracts common: lens freely permeable to glucose, metabolized to sorbitol via the enzyme aldose reductase, potent hydrophilic agents, lens fibers swell and rupture

Question 3

Minimum database

Answer 3

CBC: WNL

chem:

• hyperglycemia
• mild elevation liver enzymes
• hypercholesterolemia
• hypertriglyceridemia

urine:
-glucosuria

urine culture/susceptibility as part of minimum database!

• 24% of diabetic dogs had bacterial UTIs with no evidence of pyuria
• glucose may be substrate for bacteria
• immune system compromise with diabetic state

Question 4

Therapy

Answer 4

1) dogs are insulin-dependent
- little to no functional beta cells
- absolute insulin deficiency
2) we must provide insulin

Question 5

Remember

Answer 5

Canine and porcine insulin have identical amino acid sequences!

Also, it is uncommon for antibody to develop versus insulin and cause issues, although it did happen versus cattle insulin

Question 6

Neutral protamine Hagedorn (NPH) insulin

Answer 6

1) crystalline suspension with protamine and zinc
2) intermediate acting
3) good 1st choice for dogs (not good choice for cats)

Question 7

Lente insulin

Answer 7

1) more zinc added to delay absorption
2) mixture of short acting and long-acting insulin
3) Vetsulin
- porcine derived Lente insulin
- FDA approved for use in dogs and cats

Question 8

Protamine zinc insulin (PZI)

Answer 8

1) more protamine than NPH results in longer duration
2) ProZinc
- recombinant human insulin
- FDA approved for use in cats

Cats tend to need a longer acting insulin while dogs a shorter acting insulin

Question 9

Long-acting analogs: insulin glargine

Answer 9

1) in solution at acidic pH, precipitates at normal pH in SC tissue
- slow release of insulin from SC microprecipitates

Question 10

Long-acting analogs: insulin detemir

Answer 10

1) similar to glargine
2) reversible binding between albumin and insulin
- gradual release of bound fraction from albumin

Question 11

Goals of therapy: diabetic canine

Answer 11

1) eliminate clinical signs of diabetes mellitus
- PU/PD; polyphagia; weight loss
2) reduce risk of complications
- ketoacidosis, infection, neuropathy (cataracts don’t seem to be avoidable, eventually they occur)

Question 12

Initiate therapy-stable canine

Answer 12

1) initiate insulin (NPH or Lente)
- Ensure animals eat prior to insulin*
- 0.25-0.5 U/kg subcutaneously every 12 hours*
2) treat any complicating conditions
3) recheck clinical signs, blood glucose curve and urine in about 1-2 weeks

Question 13

Feline diabetic: differences from canine

Answer 13

1) majority have type II diabetes**
2) obesity is an important risk factor
- insulin resistance
3) occurs concurrently with other endocrinopathies
- Cushing’s, acromegaly

Question 14

Feline diabetic: differences from canine

Answer 14

1) stress hyperglycemia more problematic
- affects diagnosis and monitoring
2) different complications
- cataracts versus diabetic neuropathy
3) relative importance of dietary management
- higher in cats

Question 15

Goals of therapy: diabetic feline

Answer 15

1) eliminate clinical signs of diabetes mellitus
- 100 < BG >250 mg/dl*
2) reduce risk of complications
- ketoacidosis, infection, neuropathy
3) promote diabetic remission, if possible!

Question 16

Initiate therapy-stable feline

Answer 16

1) initiate insulin therapy
- cornerstone of management of DM and cats-optimize chance of remission
- PZI, Lente, or glargine appropriate 1st choices
- 1 U/cat SC BID
2) implement dietary management

Question 17

Oral hypoglycemic drugs

Answer 17

1) Glipizide
- sulfonylurea
- stimulates insulin secretion
2) treatment is successful in 1/3 of cats
3) **only use in situations in which owners are unwilling or unable to give insulin

Question 18

Nutritional management

Answer 18

1) cats are true carnivores and best adapted to a diet composed mainly protein and fat
2) high protein, low carbohydrate diets are ideal
- improve clinical control, increased rate of remission
3) weight management
- reversal of obesity induced insulin resistance

Question 19

Diabetic remission

Answer 19

1) maintains normal glycemia without insulin
2) usually occurs within the 1st 3 months of treatment
3) remission DOES NOT equal cure
- new sources of insulin resistance can precipitate relapse (i.e. illness)
- lifelong weight and dietary management recommended

Question 20

Ketosis

Answer 20

1) ketone bodies derived from fatty acid oxidation
2) in states of cellular glucose deficiency, ketone bodies can be used as energy source
3) As ketone bodies increase in vascular space, exceed renal threshold = osmotic diuresis=>

Question 21

Urine ketones

Answer 21

1) urine strips measure: acetoacetic acid, acetone
2) strips do NOT measure beta-hydroxybutyrate
3) ketosis indicates more prolonged cellular “starvation”

Question 22

Stable ketotic diabetic

Answer 22

1) very similar to stable diabetic
2) urine ketones present
3) clinically: still leading, still drinking, maintain hydration, no vomiting
4) if suspect ketosis with negative urine ketones, check the blood
5) most can be treated as stable diabetic
- watch more closely

Question 23

Diabetic ketoacidosis

Answer 23

1) ketosis plus metabolic acidosis = diabetic ketoacidosis
2) these animals are SICK
3) warrant immediate care = hospitalization, emergency therapy**
4) consider referral to 24 Hour Care Ctr.

Question 24

Diabetic Ketoacidosis: why are they so sick?

Answer 24

1) dehydrated:
- osmotic diuresis: glucose, ketones
- vomiting and diarrhea: acidosis
- volume depleted, GFR falls
- worsens prerenal azotemia
2) acidotic
- hydrogen ions produced to buffer bicarbonate, overwhelms buffering system (renal)
3) life-threatening if not corrected**

Question 25

Precipitating causes of DKA

Answer 25

1) concurrent disease:
- pancreatitis, UTI/pyelonephritis, HAC, pneumonia, neoplasia, renal/hepatic disease
2) diestrus
3) insulin withdrawal
4) fasting/dehydration

diabetes alone may eventually lead to DKA

Question 26

signalment and history

Answer 26

1) middle to older aged dogs and cats, no sex predilection
2) historical signs
- PU/PD/PP; weight loss
3) acute signs
- anorexia, vomiting/diarrhea, dehydration, weakness/depression

Question 27

Physical exam

Answer 27

1) dehydration (may also have hypovolemia-hypothermia, weak pulses etc.)
2) muscle wasting (especially uncontrolled diabetes)
3) variable BCS
4) poor hair coat
5) weakness/depression
6) cataracts (dogs)
7) peripheral neuropathy (cats)

Question 28

Diagnosis

Answer 28

1) hyperglycemia
2) glucosuria
3) ketonuria
4) acidosis
5) sick
6) may be initial diagnosis or may be diagnosed and previously stable diabetic

Question 29

Treatment goals

Answer 29

1) restore intravascular volume
2) correct dehydration
3) correct electrolyte disturbances
4) correct acid-base imbalance
5) reduced blood glucose concentration
6) eliminate ketones
7) address underlying diseases

ORDER IS IMPORTANT

Question 30

Fluid therapy in DKA

Answer 30

1) method of administration: IV catheter
2) rate of replacement
- maintenance + % dehydration + ongoing losses
- typically correct dehydration over 6-24 hours
- may give initial fraction of replacement volume as bolus, depending on patient status

Question 31

Fluid therapy DKA

Answer 31

1) fluid choices
- buffered crystalloid solution (plasmalyte, LRS)
- after initial stabilization: may also need maintenance solutions depending on individual patient needs
2) fluid additives
- dextrose (0-5%, depending on blood glucose)
- electrolytes (DO NOT BOLUS!)

Question 32

Potassium supplementation

Answer 32

1) initial serum potassium variable
- insulin promotes intracellular potassium shift
2) prepare for potassium to drop following insulin therapy**
3) high rates of potassium supplementation are common
- monitor frequently!
- Dose potassium on a body weight basis (not a per liter basis)

Question 33

Phosphate supplementation

Answer 33

1) phosphorus follows potassium
-both are driven intracellularly with insulin administration
2) serum phosphorus <1.5 mg/dl clinically significant
3)

Question 34

Insulin therapy

Answer 34

1) regular insulin
- rapid onset, potent, short acting
2) IV protocol
- insulin added to 0.9% NaCl administered as CRI
- per 250 mL saline: 2.2 U/kg (dogs), 1.1 U/kg (cats)

Question 35

Helpful hints

Answer 35

1) place a central line or sampling catheter
- frequent glucose and electrolyte monitoring
2) use burette for frequent changes in fluid composition
3) feeding assistance may be necessary
4) DKA may be brought on by concurrent illness, therefore LOOK FOR ONE

Question 36

Once through DKA crisis

Answer 36

1) change to longer acting insulin (if newly diagnosed, start at the starting dose)
- patient is eating and drinking
- vomiting is resolved
- acidosis is resolved
- ketosis is resolved

Question 37

To summarize

Answer 37

DKA is a serious complication of diabetes mellitus, usually brought on by one or more concurrent disease

prognosis can be good if:

1) precipitating condition can be treated
2) aggressive treatment is implemented (24-hour intensive care)

Question 38

To summarize #2

Answer 38

1) remember your priorities when treating DKA!
- Begin addressing hypovolemia and dehydration 1st
- pay attention to electrolytes
- begin cautious insulin therapy after addressing the above issues

Question 39

Diabetic monitoring: blood glucose curve

Answer 39

1) procedure: blood glucose recorded every 2 hours after insulin administration
- increased hourly if blood glucose is low in-ideally sample for 12 hours
2) mimic home environment as much as possible (minimize stress)
- feed/give insulin at home*

Question 40

Blood glucose curve

Answer 40

Parameters:

1) pre-insulin blood glucose (if possible)
2) Nadir (lowest blood glucose level in that 12 hour period)
3) duration of insulin effect
4) highest BG
5) average BG

**MUST interpret curve in light of other clinical parameters before making decisions regarding insulin administration

Question 41

Glucose curve: indications

Answer 41

1) 1-2 weeks after any change in insulin dose or formulation
2) any patient with poor control of clinical signs
3) routine monitoring in any patient every 3-6 months

Question 42

Glucose curve: pitfalls

Answer 42

1) day-to-day variability
- insulin recommendations based on blood glucose curve alone differed in 50% of cases!!
2) effect of stress hyperglycemia
3) expense
4) potential to miss hypoglycemia
- note: you are still more likely to miss hypoglycemia with other modalities (fructosamine, glucose spot-checks)

Question 43

Diabetic monitoring: fructosamine

Answer 43

1) fructosamine is the product of an irreversible reaction between glucose and the amino group of plasma proteins
- Reflects average blood glucose for past approximately 2 weeks
- use: eliminates confounding effect of stress hyperglycemia
2) limitations:
- can be normal in recent-onset DM
- reduced in hypoproteinemia and hyperthyroidism!

Question 44

Poor owner compliance

Answer 44

• *Most common cause of persistence of diabetic clinical signs**
  1) may mimic insulin resistance
  2) diagnose by history and observe the technique of the owner
• blood glucose curve after insulin administered by clinician

Question 45

Insulin under-dose

Answer 45

1) anticipate increasing dose (0.25 U/kg BID)
2) MOST diabetics will have glycemic control with 1 U/kg insulin BID or lower
- doses higher than 1.5 U/kg BID ==> suspect insulin resistance or another problem

Question 46

Insulin resistance

Answer 46

1) concurrent disease process impairs insulin activity
- action of diabetogenic hormones
2) common diseases: obesity, infection, acromegaly (cats), hyperadrenocortiscism (dogs), pancreatitis

Question 47

Insulin induced hypoglycemia

Answer 47

1) Somogyi Effect
2) etiology: hypoglycemia (brought on by insulin overdose) ==> stimulation of diabetogenic hormones ==> increases BG levels ==> rebound hyperglycemia

3) can induce insulin resistance for up to 72 hours
4) clinical signs of hyperglycemia dominate
- glucouria is common

**The body is good at protecting the brain against hypoglycemia

Question 48

Inadequate insulin duration

Answer 48

1) rapid metabolism of insulin
- duration <8-10 hours
- Nadir occurs less than 8 hours after injection with hyperglycemia (>300 mg/dl) recurring before next insulin dose