Insulin Resistance is defined as a condition in which a "normal" amount
of insulin produces a "subnormal biologic response".
Insulin resistance should be suspected whenever large doses of insulin
(>1.5 Units/kg in the dog; >6-8 units/cat)
are being administered and blood glucose is persistently elevated
(> 16.7 mmol/L; >300 gm/dl)
for most of the day, or excessive amounts of insulin
are necessary to maintain the blood glucose concentration
< 16.7 mmol/L (300 mg/dl).
Before investigating potential causes of insulin resistance, make
sure of the following:
a) The owner is storing, mixing and administering the insulin
The most common cause for persistently increased
blood glucose concentrations is
owner error in administering the insulin.
Make sure the correct syringes are being used.
This is especially important if you are using
U100 needles to administer U40 insulin
You have to make the proper conversion then.
Improper administration of insulin.
If possible, have your doctor observe you
giving the insulin to your pet.
b) There could be something wrong with the insulin.(wrong type,
bad batch, diluted,
outdated,overheated, mixed by shaking,
Insulin should be replaced every four
weeks even if there is still insulin left in the bottle.
c) Make sure the owner is following the diet and feeding schedule
d) Make sure the dose of insulin is sufficient.
e) Make sure the animal is not experiencing insulin overdose
and glucose counter regulation (Somogyi phenomenon). If insulin overdose
occurs, the body responds by secreting diabetogenic hormones(glucagon,epinephrine,
growth hormone, cortisol). These hormones induce hyperglycemia(morning
blood sugar is ususally extremely elevated). Consequently, the animal
goes through a period of hypoglycemia(weakness, lethargy, headtilt, seizure)
followed by signs of hyperglycemia(increased PU/PD). A blood glucose
curve is necessary to document this phenomenon.
f) Make sure low or impaired absorption of the insulin is not
occuring. This is primarily a problem in cats on ultralente insulin.
The blood glucose may not fail until 6-8 hours following the insulin injection.
A blood glucose curve will define this problem(you'll see postprandial
hyperglycemia that persists for several hours). OR Rapid insulin metabolism.
Insulin wears off quickly in some animals. Your pet may require a different
type of insulin or a second injection during the day, most canines require
two shots a day and many vets seem to start them at one shot a day.
g) Make sure insulin is not being rapidly metabolized (transient
insulin effect). If the insulin is rapidly absorbed from the injection
site, the duration of insulin action is not sufficiently long to achieve
adequate control of
h) Make sure the animal is not experiencing transient hyperglycemia
following a meal(consider giving an additional low dose or regular insulin
SOME PETS ARE DIFFICULT TO REGULATE
Some pets seem to require re-regulation frequently. There may be an
underlying reason to sort out.
Causes of Insulin Resistance
1. Drugs: glucocorticoids, megesterol acetate (Ovaban).
It is important to obtain a thorough drug history (including any eye or
ear medications that could contain steroids).Steroid administration (such
as prednisone, prednisolone etc.) will interfere with insulin.
2. Infections: particularly of the urinary tract and oral
Infections anywhere in the body can induce increased secretion of cortisol,
glucagon, and epinephrine, all of which can antagonize the action of insulin.
It is important to perform a complete physical examination and a urine
culture in any diabetic when insulin resistance is suspected. Because of
the relatively high incidence of bacterial infections in diabetic patients,
you may wish to administer a broad-spectrum, bactericidal antibiotic for
10-14 days if no other cause of insulin resistance is found.
3. Endocrine disorders:
hypothyroidism in dogs
hyperthroidism in cats
hyperadrenocorticsm in dogs and cats (cushing's disease)
acromegaly (hypersecretion of growth hormone) (cats)
diestrous (intact female dogs: improvement in control of diabetes is
apparent within a week after ovariohysterectomy)Progesterone also interferes
with insulin. Unspayed female diabetics should be spayed once they are
4. Obesity: results in internalization of insulin receptors;
decrease insulin receptor binding affinity; postreceptor defects
5. Concurrent illness: with any concurrent problem, counter
regulatory hormones (glucagon, glucocorticoids, catecholamines, growth
hormone) can be secreted and lead to insulin resistance.
cancer (pheochromocytoma, glucagonoma, mast cell tumor, lymphoma)
6. Presence of insulin-binding antibodies:
Insulin resistance caused by anti-insulin antibodies is likely rare
in small animals and is difficult to diagnose. In the dog, beef containing
insulin products are more likely to be antigenic vs pork insulin or recombinant
human insulin. In the cat, pork insulin and recombinant human insulin
are likely to be more antigenic vs beef or beef-pork products.
7. Absorption problems (giving a shot subcutaneously does not guarantee
that it will get absorbed. Sometimes giving the insulin in a different
spot will make all the difference.
The following is from Auburn University College of Veterinary Medicine
Insulin resistance describes the condition in which the pancreas is
capable of producing insulin, but the cells are insensitive to it. If insulin
is the “key” which unlocks the “gate” through which glucose must pass to
enter cells, then insulin resistance results when there are too few “gates”
or the ‘locks’ on the gates are “rusted shut” and are difficult to open
despite the presence of insulin. There are many conditions which may predispose
to the development of insulin-resistant diabetes or which may unmask a
mild, subclinical, or transient diabetes that already exists. These include
pregnancy, overproduction or over-administration of steroids like cortisone
or prednisone, overproduction of growth hormone (acromegaly), infections,
prolonged or severe stress, and many others.
Alternatively, these conditions may increase the dose of insulin required
to properly regulate a diabetic already undergoing therapy. A diabetic
patient which requires an insulin dose higher than 1-2 units per pound
of body weight per injection to maintain normal blood sugar levels is considered
to be “insulin-resistant”; every effort should be made to identify possible
conditions which may be increasing the insulin requirement. Sometimes,
just a prolonged untreated bladder infection may be enough to dysregulate
an otherwise well controlled diabetic. If your dog has recently required
a significantly increased dose adjustment to re-regulate blood sugar levels,
or is difficult to regulate despite high insulin doses, have your pet re-evaluated
by your veterinarian. Although there are many reasons why a diabetic may
be difficult to regulate, the possibility of insulin resistance must be
considered once other potential causes have been investigated and ruled