Five Principals

• Tight control is not essential and not even desirable
  • Ideal for dogs 100-200 mg/d
  • Ideal for cats 100-300 mg/dl
  • Because
    • Cats do not get significant vascular or renal disease secondary to diabetes
    • Cats do not get cataracts due to diabetes
    • The toxic level or glucose is very high
    • Neuropathy goes away with time
  • Urgency principal allows for oral medication trial
• Hyperglycemia is better than hypogycemia
  • Toxic level of glucose is very high (up to 1500 in humans)
  • hypoglycemia kills
• Urgency
  • As long is the cat is not ketoacidotic, it is not likely to die soon
  • This permits a one month drig trial with an oral hypoglycemia drug
  • Permits us to to gradually work into regulation
• Clinical signs are extremely important in regulating and maintaining a diabetic cat
  • "Consistency is the key to doing the impossible - same food (brand and quantity), indoor only (activity) and stress"
  • "Look at the cat"

Diagnosis

• The diagnostic triad
  • Hyperglycemia
  • Glucosuria
  • Clinical Signs
    • PU
    • PD
    • PP
    • Weight Loss
  • You can use ketostix with blood
  • 1/2 of all cats are ketoacidotic according to literature. In actual practice, this is more like 5%

Stress hyperglycemia

• Even mild stress
• No signs of diabetes; no glucosuria (at the time of stress)
• Fructosamine levels
  • Can be used to differentiate in 90% of cases even though there is some overlap
  • Represents average reading for last two weeks
    • 110 - 300 - normal
    • 170 - 400 - stress
    • 200 - 850 - diabetic
  • Not accurate with hyperthyroidism
• For as long as 24 hours

Transient diabetees

• Insulin resistance occurs
• May occur slowly
  • Client education
  • 15-20% of diabetic cats
  • Diabetes almost always recurs
• Destruction of beta cells occurs by degree
• Time driven
• Oral hypoglycemics can hasten destruction of beta cells

Types of diabetes

• Type I
  • Insulin dependent
• Type II
  • Oral medications can be used
  • May be transient
  • Usually progresses to type I

Etyology

• Autoimmune
  • Common in dogs
  • Not common in cats
• Amyloid deposition
  • Amyloid is deposited in beta cells causing their destruction
  • Most common form in cats
  • Most are insulin dependent
• Secondary
  • The result of underlying pancreatic disease combined with other primary disease or an insulin antagonist drug
    • Cushing's
    • Acromegaly
    • Hyperthyroidism
    • Ovaban
    • Steroids
  • May be transient, if the disease or drug is removed
  • Chronic pancreatitis may result in enough beta cekk destruction to cause diabetes; exocrine pancreatic insufficiency (EPI) may also occur
    • Trypsin-like immunoreactivity (TLI): feline specific test by Dr. David Williams 1-409-862-2861 to detect pancreatitis

Goals of Therapy

• Establish glucose level of 100-300
  • Hyper is better than hypo
• Resolve clinical signs
• More important than glucose level
• Signs resolved
• Healthy
• Weight Stabilized

Urgency of treatment

• Some cats have lived 6 to 24 months without therapy
• Cataracts do not develop in cats they way they do in humans and in dogs
• Toxic level of glucose is 20-1500 for humans, possibly higher for cats
• Cats not in ketoacidosis are not critical

Treatment  -5 Steps

• Step 1: Client education - requires more long term treatment than any other disease
• Clients must be educated on the following
• The implications to the cat
• The implications to the owner
• The importance of consistency
• Likelihood of dysregulation
• Hyperglycemia is always better than hypoglycemia
• Spontaneous remission
• Hypoglycemia
• Insulin administration
• When to give insulin; when no to give insulin
• The proper food type and feeding schedule
• How to monitor the cat at home
• When to return for rechecks
• Step 2: Test for three diseases
• Feline TLI
• To test for chronic pancreatitis and for exocrine pancreatic insufficiency
• Also run B12 (cobalamin) and folate levels
• 95% of cats with EPI have undectable levels of B12
• Folic acid deficiency is rare
• Treatment for EPI (Exocrine Pancreatic Insufficiency)
• Pancreazyme or Viokase or 1 oz of raw pancreas with each meal
• Do not use tablets as they are not broken down fast enough
• Preincubation with powder does not increase the effect and decreases palatability
• Treatment for Cobalamin deficiency
• Give B12 1m or sub-q (100-250 mcg) every 7 days until the serum level is normal (~4 weeks)
• Then give every other week for 2 doses then every 4 weeks for doses, then recheck the serum
• Treatment for folic acid deficiency
• Give the folic acid at 1mg/cat/d; recheck serum in 30 days.  If low, treat another 30 days.  When the serum level is normal, discontinue treatment
• Hypertension
• Recently found to be of high incidence in diabetic dogs
• Treat with amlodipine (~0.625 mg/cat/d to effect)
• Can add an ACE inhibitor (benazepril or enalapril) if needed
• Step 3: Diet
• Use a high fiber diet and choose it based on the body weight:
• Overweight
• Hills r/d or Purina's O/M
• Normal
• Hill's w/d or Purina's OM
• Thin
• Renal diets with added fiber (see below)
• Other fiber sources
• Vetasyl
• Canned pumpkin (1 tablespoon q12-24h)
• Sugar-free Metamucil (psyllium)
• Consistency is more inportant than high fiber
• Better to feed a bad diet consistently than the right diet inconsistently
• Free choice feeding is the preferred method for diabetic cats
• Step 4: Antibiotics
• Bacterial infections are common in diabetics (pyeonephritis, cystitis, cholangiohepatitis, pancreatitis)
• If they are not controlled, regulation is nearly impossible
• Treat with a broad spectrum antiobiotic for two weeks: Clavamox may be the best choice
• Step 5: Insulin
• When to begin
• Presence of ketosis
• Emaciation
• Failure of oral drugs
• Oral drugs cannot be given
• Initially
• Choices
• PZI: Beef/pork (1-800-374-8006)
• Blue Ridge Pharmaceuticals
• Investigational use
• PZI: Pure beef (Sugarcats.com personal choice, see PZI Info on the menu)
• NPH Iletin I: beef/pork (discontinued)
• NPH Iletn II: Pork (to continue long term)
• Humulins: Human cell origin (L, N, U)
• 33% of cats don't absorb it consistently
• Goes out of suspension quickly
• Initial dose: 2 U BID Sub-q for most 8-10# cats
• Treat for 5-7 days then recheck in the early AM with out insulin being given
• Record:
• Hours post insulin
• Weight (compare to previous)
• Clinical signs
• Blood glucose
• If the bg is >350 mg/dl, increase to 3 U BID and repeat in 5-7 days
• When the bg is <350 mg/dl, keep for a glucose curve
• Exception: If the bg is still > 350 mg/dl on the third recheck, do a glucose curve to rule out rebound hypoglycemia (Somogyi)
• Each time you recheck the cat, check more than just bg
• If the bg and the clinical signs conflict, believe the clinical signs
• You may also use a fructosamine on these cats, but ideally, the cat should be on a consistent dose of insulin for 2+ weeks

The Glucose Curve

• To identify
• The peak time of insulin effect
• The level of the nadir
• The likelihood of reboud hypoglycemia
• The allows you to decide
• The insulin type to use
• The insulin dosage
• The dosing interval (q24h vs q12h)
• Procedure
• Give the same dose for 5+ days
• Begin early in the morning (as close to normal time of insulin administration as possible)
• Do not keep the cat waiting or contribute to its stress
• Ask about clinical signs:  factor this information into your interpretation
• Take an initial glucose reading
• Administer the insulin at the same dose
• Feed the cat.  If it is free-feeding, do not withhold food
• Take glucose readings every 1.5 to 2 hours to determine
• The time of peak insulin effect (peak time)
• The nadir
• Whether rebound hypoglycemia is occurring
• When the nadir is reached, take 1-3 bg readings at 30 minute intervals for verification
• Usually complete in 6-8 hours
• If the cat does not eat:
• The curve will be lower than at home
• Have the owner feed the cat in the exam room
• Better: feed the cat just before leaving home if it is a meal-fed cat or do not restrict food overnight or that morning if it is a free-fed cat
• Minimize the environmental stress.  Cage the cat away from sign or sound of barking dogs
• Glucose Determinations
• Use an Accu-Check glucometer
• Use  Prestige Glucometer from Palm Lab Inc
• 1-877-725-6522
• Animal validated
• Works on heparnized blood
• Use non-heparnized blood.  Do not collect blood in heparnized capillary tubes
• Blood collection
• Protect those veins;  you will need them for years to come
• Preferred:  25 ga needle, cephalic veins, alternating sites moving up the legs
• Do not place IV catheters in the cephalic veins unless really needed

• To determine the dosing interval
• Peak Time:  Time of sinulin injection until the nadir is reached
• If < 5 hours: TID dosing or a longer acting insulin
• If 5-8 hours: BID dosing
• If > 8 hours: OD dosing
• To determine the dose
• Nadir
• If < 100 mg/dl (5.6 mmol/L); decrease the dose
• Will be lower at home due to the inevitable stress in the hospital
• The Range
• The lowest to the highest glucose levels
• The Range Midpoint
• Determines the dose or if problems exist
• Ideal: at 200 mg/dl
• Good: 150-250 (8.3-13.9)
• If < 150 (8.3) reduce the dose
• If 150 - 250: No change
• If >250 (13.0)
• Dose is too low:  Increase the dose as long as the nadir is > 100mg/dl
• Insulin problems exist:  Inactivated insulin, insulin not mixed, poor injection technique, poor absorption
• Insulin resistance exists: Concurrent disease (Cushing's, acromegaly, hyperthyroid, systemic illness), insulin antibodies
• The cat is stressed
• The fractious or difficult cat
• Manual restraint :(
• Tranquilizers :(
• Hospitalize for 3 days with or without a jugular catheter
• Outpatient curve :(
• Fructosamine + clinical signs

Managing Diabetes in a Fractious Cat

• What won't work: Blood glucose testing
• What is reliable
• Clinical signs
• Urine glucose testing at home
• Fructosamine testing

Oral Hypoglycemics

• Reasons to use
• Owner's fear of needles
• May prevent euthanasia
• Reasons not to use
• Success rate (only 30% of cats have success)
• Owner cannot give pills
• Cat will not take pills
• Islet Associated Polypeptide (IAPP)
• Deposited in beta cells, converted to amyloid, destroys more beta cells
• Dose
• Begin at 2.5 mg/10# BID for one week
• Recheck bg
• If not response, increase to 5mg/10# BID for three weeks
• Check bg weekly
• May increase to 7.5 mg/10# TID
• Side-effects
• Vomiting
• Hypoglycemia (unlikely)
• Hepatoxicity
• Generally avoided by starting at the 5 mg BID dose for the first week

Hypogycemia

• Clinical signs
• Mild form: Unresponsive at peak time
• Severe form: Coma, seizures, death
• Treatment
• Oral corn syrup
• IV 50% dextrose (slowly to effect)

Dysregulation

• Independent Dysregulators
• Improper measuring of insulin
• Improper injection technique
• Inproper storage/handling of insulin
• Estrus or pregnancy
• Cushing Disease
• Acromegaly
• Insulin incompatibility
• Concomitant Disease
• Contributing Dysregulators
• Inconsistent caloric intake
• Inconsistent activity level
• Inconsistent dosing interval
• Poor home monitoring
• Improper diet (high in sugar, low in fiber)
• Multicat household
• Boarding
• Obesity
• Use of steroids

Miscellaneous Tidbits

• Have your client read the client information handout before your discussion with them
• Decreases discussion time
• Increase likelihood that you will address their questions and concerns - fewer follow-up phone calls
• Monitoring
• By glucose readings using the peak and nadir (mini-glucose curve)
• If you do not do bg readings at the peak or nadir, at least do them at the same time each visit
• Fructosamine
• Excellent < 350
• Good 350 - 450
• Fair 450 - 600
• Poor > 600
• May fail if Somogyi is occurring
• Shaking Insulin
• Be sure all of the insulin crystals are off the bottle even if vigorous shaking is needed
• Dilution of insulin
• Normal saline: only good for 24 hours
• Proper diluent (supplied by manufacturer); only good for 30 days
• Do not use sterile water for injection
• Detecting glucose in urine: Wet Kitty Litter Method (Feline Practice, November 1994)
• Place equal amount for wet kitty litter and water in a cup and stir.  Put urine dip stick in the liquid
• Negatives are really negative
• Positives are half of their actual value
• Can also be used on dried litter
• Does not work on clumping letter
• Periodontal Disease
• Insulin dose can decrease 25% after teeth cleaning and antibiotics
• Clean the teeth as soon as possible; even before regulation is achieved
• Managing the Hypoglycemic Crisis (Norsworthy Protocol)
• Corn syrup: 1 tablespoon per 10# (to effect)
• Give now; repeat in 20 minutes.  If not response, do IV treatment
• Following IV treatment
• Continue dextrose therapy for 24+ hours
• IV 5% dextrose
• Food
• Determine why it happened before resuming insulin
• Insulin Incompatibility
• One of the most common causes of dysregulation
• There is not a high dose or a low dose that can be ruled out
• Due to the insulin source: beef/pork/insulin
• If it occurs, you must change the insulin source to solve the problem
• Clinical signs
• Temporary response
• An increasing dose is needed every few days
• The dose often reaches 10-15 u/10# BID
• Diagnosis
• Stop insulin levels for 24 hours and perform a serum insulin level
• No antibody formation: very low serum insulin (no incompatibility)
• Antibody formation: high serum insulin (incompatibility)
• Treatment
• Change to another insulin
• Consquences
• Dysregulation
• Renal failure (glomerulonephritis)
• Surgery on a Diabetic Cat
• For short procedures: hyperglycemia is always better than hypoglycemia
• Feed the cat at 4-6 pm the day before the surgery and give one-half dose of insulin
• Give no food or insulin the morning of the surgery
• Use an anesthetic that permits rapid recovery (isoflourane by mask then via endotracheal tube)
• Give one-half dose of insulin at the first feeding then the full dose at the next feeding