Obesity is a common cause of insulin resistance in cats and probably plays a role in the development of diabetes in many patients.
Adipose tissue is highly metabolically active and releases numerous chemicals (e.g. adiponectin, leptin) that directly impact the effect of insulin.15,16 Controlled weight loss is essential in obese cats, with a target loss of 1% to 2% per week. In addition to calorie restriction,
the nature of the ingested energy must be considered. Low-carbohydrate, high-protein diets are now recommended for diabetic
cats, as improved glycemic control has been documented.9,17
Concurrent infections are commonly noted in feline diabetics and can certainly impact these cats' response to insulin. Urinary
tract infections appear to be prevalent in diabetic cats, particularly females, with an 18% incidence cited in one recent
report.18 Clinical signs of lower urinary tract disease may be noted by the client, but the possibility of a urinary tract infection
should not be discounted simply because the cat is not dysuric, pollakiuric, or hematuric.
If an insulin-resistant cat has severe periodontal disease, it may be advantageous to address this problem. Chronic infection
in the mouth may trigger the release of counter-regulatory hormones such as cortisol, with resultant persistent hyperglycemia.
Sterile inflammatory diseases cause insulin resistance through a similar mechanism. Pancreatitis, particularly the chronic
form, appears to be common in feline diabetics. The feline pancreas-specific lipase activity test (Spec fPL—IDEXX Laboratories)
has a high sensitivity and specificity in moderate to severe pancreatitis but may yield normal results in cats with mild forms
of the disease.19 Abdominal ultrasonography is also a useful tool for evaluating pancreatic inflammation in cats. Managing cats with pancreatitis
can be difficult, but pain control and nutritional support are often beneficial. Some cats with chronic pancreatitis develop
exocrine pancreatic insufficiency. This is best identified with a tryspin-like immunoreactivity determination and then managed
with powdered enzyme products.20
Another important consideration is concurrent endocrinopathies. Hyperthyroidism is a prevalent endocrine disorder in geriatric
cats and may impact the effectiveness of exogenous insulin.21 Many of the signs seen with thyroidal disease in cats, namely polyphagia, weight loss, polyuria, and polydipsia, mimic those
of uncontrolled diabetes mellitus, which can lead to delayed recognition. In most cases, hyperthyroidism is easily confirmed
by an increase in basal serum thyroxine (T4) concentration; however, this concentration may remain within the reference range in early cases. If the T4 is above the middle of the reference range in a poorly regulated diabetic cat, it may be helpful to measure free T4 by equilibrium dialysis (ED). This is not recommended as a screening test, however, as some euthyroid cats have modest increases
in free T4 ED.
Acromegaly due to a pituitary adenoma is a well-recognized cause of insulin resistance in cats.22,23 Progressive weight gain despite poor diabetic regulation is a hallmark. Specific physical changes, such as enlargement of
the tongue and feet or separation of the incisors, are often seen later in the disease. Recent studies have shown that measurement
of serum insulinlike growth factor-1 (IGF-1) is a useful screening test for cats, although an elevated concentration may not
be definitive.24,25 The University of Minnesota offers a feline growth hormone assay that may be more useful, although there is little information
available regarding this test. If either GH or IGF-1 concentrations are supportive of acromegaly, the next step would be imaging
of the pituitary region (with either computed tomography or magnetic resonance) to identify a mass.26
Hyperadrenocorticism is much less common in cats than in dogs, but it is associated with profound insulin resistance. Cats
can develop this disease as a result of oversecretion of adrenocorticotrophic hormone (ACTH) by the pituitary gland or a functional
adrenocortical tumor. Again, many of the clinical signs (e.g. excessive thirst and appetite) associated with hyperadrenocorticism mimic those of uncontrolled diabetes. Therefore, practitioners
should pay careful attention to physical changes such as loss of abdominal muscle mass or skin fragility, as these strongly
suggest hyperadrenocorticism.27 The most reliable diagnostic test for suspect cats is the low-dose dexamethasone suppression test (LDDST). The dose of dexamethasone
used for the LDDST in cats is 0.1 mg/kg, which is much higher than the canine dose. Abdominal ultrasonography is often the
easiest way to identify an adrenal tumor. If both adrenal glands are enlarged, pituitary imaging should be considered.
Concurrent medications should always be carefully evaluated in insulin-resistant cats. Glucocorticoids and synthetic progestins,
such as megestrol acetate and medroxyprogesterone acetate, are potent insulin antagonists.28 As mentioned earlier, anti-insulin antibodies should also be considered in a cat with insulin resistance.
The difficult diabetic cat poses some unique challenges, but careful data collection and patient evaluation will often uncover
the cause of poor glycemic control. A step-wise, logical approach should be followed (Table 3) so that straightforward problems are effectively addressed before more complex diagnoses are considered.
Table 3. Suggested Workup for Insulin-Resistant Diabetic Cats.
Audrey K. Cook, BVM&S, MRCVS, DACVIM, DECVIM
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
Texas A&M University
College Station, TX 77843