Diabetes in cats, part 1--using the ultraloose approach (Proceedings)

The big picture

• Successful management of diabetic cats requires a multipronged approach.

• Diabetes does not occur in a vacuum.

• The diabetic cat usually has other needs that must be addressed before diabetic regulation can be achieved.

• Chronic pancreatitis.

• Periodontal disease.

• Bacturia

• My pre-treatment protocol

• CBC + Chemistry Profile + UA

• FeLV/FIV tests if exposure likely

• fPLI  @ IDEXX

• Urine culture

• Dental prophy PRN

• Usually after 1-3 weeks of treatment with insulin and diet.

• 1-2 weeks of antibiotics

Insulin choices

• Regular – for use in diabetic ketoacidosis only

• Lente (Vetsulin)

• 100% pork

• U-40 concentration

• Best for dogs but approved for cats

• 8 hour duration of action

• Currently not available in the U.S.

• NPH (Humulin-N)

• Intermediate acting like lente

• Human origin so some antibody problems

• Protamine Zinc (ProZinc)

• U-40 concentration

• A recombinant product

• No antibody formation

• Constant supply

• My insulin of choice for 35+ years

• Pricing

• Our cost: ~$60

• Our retail: ~$90

• Glargine (Lantus)

• Initial interest in this product based in Europe and Australia

• Law requires the use of a veterinary approved product first, if one is available

• Vetsulin/Caninsulin was (is) the only veterinary product but it has a DOA of only 8 hours so control of many cats was (is) a problem.

• There (was) is no protamine zinc product available.

• Many cats have a very good response to it.

• It should be given q12h, but if the owner will only treat q24h, it is the best choice.

• U-100 concentration; use 0.3 cc U-100 syringes.

• Do not dilute with anything; any pH change inactivates it.

• Retail: ~$75-95 per 10 ml bottle.

• A DNA recombinant product so not an antibody problem.

• Observations by Jacquie Rand (website)

• “Many cats have a negligible glucose lowering effect in the first 3 days (do not increase the dose), although by day 10 after beginning insulin, most cats have good glycemic control.”

• “For many cats, the time at which the nadir (lowest) glucose concentration occurs is often not consistent from day to day, or between cats. Sometimes it occurs between the two doses, but sometimes the nadir occurs around the time of the next dose.”

• “Most commonly the highest glucose concentrations occur in the morning and the lowest in the evening.”

• “Some cats consistently have their nadir glucose concentration in the evening just before the next insulin injection, and less commonly, it occurs around the time of their morning injection.”

• Pharmacodynamics of Insulin Detemir and Insulin Glargine Assessed by an Isoglycemic Clamp Method

• “The average time-action curve (Fig. 1K) suggests that both analogs are relatively flat curves. Considering the individual time action curves, however, it is clearly not safe to assume that either insulin detemir or insulin glargine is long-acting and flat in any given patient. Fig. 1A-J.”  

• The duration of action in 50% of the cats in this study was less than 12 hours.

• The duration of action of 30% was equal to or less than lente.

• Glargine in humans

• Used as a background insulin.

• Short-acting and intermediate-acting insulins are given several times per day on a PRN basis.

• It was not designed to be the sole insulin product for diabetic humans.

Tight control approach

• Ref: J Feline Medicine & Surgery, September 2009

• Protocol

• 55 diabetic cats were treated with a tight glucose control protocol

• Home glucose testing daily

• Glargine

• Canned ultra low, carbohydrate diet

• Results

• 84% went into diabetic remission if the protocol was started less than 6 months after the diagnosis was made or they had been on steroids prior to the onset of diabetes.

• Details of the protocol

• Diet: ultra-low carbohydrate diet

• Less than 10% metabolizable energy from carbs

• Canned only

• Most were commercial diets

• Some were home-made or raw meat diets.

• Insulin

• Glargine

• The only long-acting insulin available in Germany (site of study).

• Glucose Testing

• Glucose values were determined daily by the owner using a human glucometer

• An algorithm was given to the owners to direct dose changes.

• The average number of glucose tests performed per days was 5.

• Range of 3-7.

• At least 3 times required to be in the study.

• My assessment

• This study shows that diabetes in cats can be well controlled or eliminated (remission) under ideal circumstances of an ultra-low carbohydrate diet, a long-acting insulin, and a rigid protocol.

• However, its practicality is highly questionable for the vast majority of my clients.

Traditional loose control approach

• Diagnosis

• Diagnostic triad: hyperglycemia, glucosuria, and appropriate clinical signs

• Confirmed with fructosamine.

• Management

• Insulin and a low carbohydrate diet are started, and the cat is discharged for home treatment.

• Some hospitalize the cat to get it regulated.

• The owner monitors the cat's blood glucose 2-14 times per week per your instructions.

• The owner calls for recommendations on dosage changes based on numbers gathered at home (home glucose testing).

• The cat is checked by you:

• 1-3 times during regulation.

• Every 3-6 months thereafter.

• Anytime the home glucose numbers are outside 100-300 mg/dl.

• Each recheck includes a glucose curve and possibly a fructosamine. The average cost is $300+ for the recheck.

Norsworthy ultra loose control approach

• Why I modified the Traditional Loose Control Approach

• Too many euthanasias due to the personal commitment required of the owner, the expense, and the hassle to the cat.

• Disappointment with results of glucose curves.

• Concerns about home glucose testing

• Too much emphasis placed on blood glucose readings instead of a combination of clinical signs and blood glucose readings.

• Owners frequently expect to report the results of their home testing, get a recommendation over the phone, and pay nothing for the consultation.

• Owners taking over the case and not returning the cat to me for its care.

• Built on the premise that …

• Cats tolerate hyperglycemia with minimal/tolerable clinical signs.

• Cats do not have significant complications from diabetes such as cataracts, peripheral vascular disease, and renal disease.

• Cats tolerate hypoglycemia with no or minimal clinical signs.

• Most cats with glucose values in the 50s have not clinical signs

• But, don't over-appreciate this fact. Severe hypoglycemia can be serious to fatal.

• There is great emphasis on clinical signs.

• “Glycemic control is attained when clinical signs of diabetes have resolved, the cat is healthy and interactive in the home, its body weight is stable, the owner is satisfied with the progress of therapy, and, if possible, the blood glucose concentrations range between 100 and 300 mg/dl throughout the day.”  Feldman and Nelson, 1996, p.363.

• Initial Regulation (non-ketoacidosis)

• Initial Insulin Dose

• If < 400 mg/dl (22 mmol/L): Low carb diet only

• Canned DM (Nestle Purina) is superior

• If > 400 mg/dl (22 mmol/L): 0.5 u/kg BID SC

• Most cats: 2 U BID

• Send the cat home for treatment for 5-10 days (usually 1 week).

• First Recheck

• At 12 hours post-insulin

• Goals

• Resolution of clinical signs

• Glucose = 300-350 mg/dl (16.5-19.5 mmol/L)

• Record 4 things

• Hours post-insulin (12 or close)

• Weight (compare with previous)

• Clinical signs: PU, PD, PP, How Feeling

• Check blood glucose

• If bG < 350 (19.5) and clinical signs gone, continue this dose and recheck in one week (cat may be regulated).

• However, we do not expect regulation this quickly.

• Caution: cats that seem to regulate in one week usually go into remission within the next 1-3 weeks.

• If bG > 350 (19.5)

• The dose is too low. This is the expected result at this time.

• Increase the dose to 3 u BID and send home for another 5-10 days.

• Second Recheck

• Weight, appetite, PU/PD, how feeling?

• Check glucose level

• If < 350 (19.5) and clinical signs are gone, continue this dose and recheck in 1 week (may be regulated)

• If > 350 (19.5) and clinical signs are present, increase the dose again for 1 week.

• Third Recheck

• Weight, appetite, PU/PD, how feeling?

• Check glucose level

•  If < 350 (19.5), continue this dose and recheck in 1 week.

• If > 350 (19.5), increase the dose again and send home.

• Continue until regulated.

• Each time you recheck the cat, check more than just the blood glucose because the blood glucose is affected by diet, exercise, stress, etc.

• Ask about clinical signs: urine, water, appetite, how feeling

• Check the weight.

• Monitoring diabetic cats is much more than looking at bG values.

• Long-Term Management

• Rechecks are on a PRN basis but not more than 3 months apart (in theory).

• Most occur ~ q3-6 weeks.

• Recheck Exam

• History of issues related to DM: PU, PD, PP, WL, How Feeling?

• Physical exam

• bG at peak insulin point: 12 hours post-insulin.

• Goals

• bG 300-350 mg/dl at peak time

• Control of clinical signs

• If bG is high and clinical signs are gone, put more credibility in clinical signs.

• Fructosamine testing for stress hyperglycemia cats.

• If bG is low (<250 mg/dl) and the clinical signs are gone, the either the dose is too high or the cat is heading for remission. Watch this cat carefully over the next 1-3 weeks with weekly rechecks. Alert the owner to the signs of hypoglycemia.

• If bG is <150 mg/dl, stop insulin and recheck in 2-5 days to see if it is in remission.

• Results

• Many cats have bG levels up to 450 mg/dl with no or minimal clinical signs.

• ~30% go into remission

• Usually within the first month of treatment.

• More if on canned low carb diet.

• More if recent steroids.

• Hypoglycemia is rare.

• Most live 3-6 years and die of non-diabetes related disease.

• 80+% are over 10 years at the time of diagnosis.

• Many are over 14 years.

• #1 cause of death: euthanasia.

• Not regulated to owner's satisfaction: poor quality of life.

• Too expensive.

• Too much commitment required

• Summary of the Norsworthy Approach

• Realize that DM in cats is due to:

• Lack of insulin production

• Insulin resistance

• Diagnose and treat diseases causing insulin resistance.

• Chronic pancreatitis

• Periodontal disease

• Infections anywhere

• Place emphasis on two things:

• Clinical signs (PU/PD/PP/WL)

• Glucose levels

• Have a tolerance for hyperglycemia if the clinical signs are controlled.

• Clinical signs are more important than glucose levels.

• Do not perform glucose curves.

• Do not do home glucose testing by the owner.

• Use protamine zinc insulin (ProZinc); no glargine or lente

• Only use fructosamine levels uncommonly (for stress hyperglycemia cats)

• Have owner feed, inject, and observe

• I decide on insulin dose changes based on client and patient visits/exams.