Insulin in Cats: Which One?
P. Jane Armstrong,
Diabetes mellitus is the
second most common endocrine disorder in cats, (behind hyperthyroidism), with
an estimated incidence of 1 in 200 cats. Diabetes occurs in a wide age range of
cats, but most cats are over 8 years of age when diagnosed. Neutered males are
affected most frequently and obesity is a risk factor. Genetics may play a role
in some breeds (e.g., Burmese cats in
Insulin Preparations
There are three general types of
insulin: Human recombinant insulin (e.g,. Humulin, Novolin), animal-source insulin (e.g., pork regular
insulin and 90% beef-10% pork PZI insulin), and synthetic
insulin (e.g., glargine). Insulins are categorized based on their onset
and duration of action in human patients as:
1. very fast-acting (e.g., Humalog and
Novolog)
2. fast-acting (e.g., Humulin R or
Novolin R)
3. intermediate-acting (e.g., the lente
series of insulins, as well as PZI and NPH and pork Lente [Vetsulin])
4. long-acting (e.g., Humulin U and
Insulin detemir [Letemir])
5. ultra long-acting (Lantus
[glargine])
6. mixtures (e.g., Humulin 70/30 which
is 70% NPH and 30% regular insulin)
Production of lente and ultralente
insulins has recently ceased due to waning use in human diabetics. Pork-origin
NPH insulin has also recently left the market. Insulin glargine (Lantus,
Aventis Pharmaceuticals) is a relatively new,
synthetic, “peakless” insulin that differs from human insulin in that one amino
acid is replaced by glycine and two arginines. Insulin glargine is currently
recommended in human diabetics as a basal insulin to
be administered once daily, at bedtime, with the goal of inhibiting hepatic
glucose production. This ultra long-acting insulin analog forms microprecipitates
at the site of injection from which small amounts of insulin are slowly
released. This effect is a property of the low pH of the injected insulin.
Most insulin preparations are
available as 100 units/ml (U-100); some are available
as 40 units/ml (U-40). Insulin syringes are calibrated in units and must
match insulin concentration (e.g., use U-100 syringes for U-100 insulin).
Low-dose U-100 syringes are available (0.3 ml, 0.5 ml) and can be very useful
for cats. Many insulin preparations can be diluted to facilitate more reliable
administration of small volumes of insulin, but it is important to use a
manufacturer-approved diluent and follow the manufacturer’s guidelines for
duration of storage of diluted insulin (generally one month maximum). Insulin
glargine cannot be mixed with other insulins or diluted, as altering the pH
alters the absorption characteristics.
Unlike other insulins, glargine does
not need to be kept refrigerated. Glargine has a shelf life of 4 weeks when
kept at room temperature. When refrigerated, opened vials can
be used for at least 6 months. If an insulin pen is used, the
manufacturer recommends that the pen be kept at room temperature, as
temperature changes associated with refrigeration alter the volume of insulin
delivered by the pen.
Insulin Selection
Until recently, most
endocrinologists recommended starting diabetic cats on either recombinant lente
insulin or PZI of beef/pork origin. Insulin glargine has recently replaced
lente and PZI as the insulin of choice in cats. A prospective study was done comparing results with
lente, PZI, and glargine in diabetic cats. Twenty-four consecutive newly
diabetic cats were enrolled in the study and randomly assigned to receive
therapy with glargine, PZI or lente insulin. All were fed a low-carbohydrate
diet. Diabetic remission was achieved in 8/8 cats receiving glargine, 3/8
receiving PZI, and 2/8 receiving lente. Diabetic remission occurred within 4
months in all cases, with the median time to remission being 3 weeks. The
results from this study suggest that glargine is a better choice than PZI in
diabetic cats because glycemic control was better and diabetic remission
(reversion to a non-diabetic state) rates were higher.
Studies in healthy cats suggest that
insulin glargine and PZI
have similar pharmacokinetic properties. Studies of glargine in
diabetic cats have yet to be reported, but this insulin appears to have a duration of effect ranging from 10 to 16 hours in most
diabetic cats, with significant suppression of blood glucose for up to 24
hours. Although many cats may potentially be able to be maintained on
once-daily dosing with glargine, the limited data available suggest that
optimal glycemic control with minimal risk of clinical hypoglycemia occurs with
twice-daily dosing.
Beginning
Therapy with Insulin Glargine
Insulin glargine should be dosed according to initial
blood glucose at diagnosis and ideal body weight. If the blood glucose is equal
to or greater than 360 mg/dl, start with 0.5 U/kg twice daily subcutaneously,
and if the blood glucose is less than 360 mg/dl, start with 0.25 U/kg twice
daily. A 12-hour serial blood glucose curve should be obtained with samples
taken every 4 hours. Because of the long duration of action and likely overlap
on insulin action, the dose should not be increased for the first week. The
dose should be decreased, however, if blood glucose concentration drops below
the reference range. Note that many cats have little decrease in blood glucose
over the first 3 days of treatment with glargine, even if diabetic remission is
achieved within 4 weeks.
Newly-diagnosed non-ketotic diabetic cats are
typically hospitalized for 3 days to begin therapy with insulin glargine or the
owner may elect to monitor blood glucose at home for the first 3 days to check the
initial response. If the cat was admitted with ketoacidosis, stabilize the cat
with regular insulin according to described protocols, and use the above
guidelines once the patient is judged ready to receive longer-acting
subcutaneous insulin injections. It is important to search diligently for
concurrent disease in all newly-diagnosed diabetic cats as the advanced age of
most diabetics predisposes to other diseases and because some diseases
predispose to diabetes.
Monitoring
Response to treatment can be evaluated in a variety
of ways, including clinical signs, changes in body weight and water intake, and
blood glucose results. Repeat 12-hour blood glucose curves are obtained at
weeks 1,2, and 4 and then as required. Adjustments in
insulin therapy are made gradually until an effective insulin treatment
protocol is identified. Dosage changes are made based on a number of blood
glucose parameters and, ideally, changes should be based on more than one
parameter. The preinsulin blood glucose has been found to be important when
using glargine or PZI because of a persisting effect from the previous
injection and the possibility of diabetic remission. The preinsulin blood
glucose is used to decide whether to continue to administer insulin. Nadir (lowest) blood glucose can be used to
adjust the dose, as with other insulin types. Measurement of water intake at
home is simpler, less expensive and less stressful than measuring serum
fructosamine concentration, and correlates better with daily blood glucose
concentration. Glargine offers new hope for diabetic cats that are fractious,
as dosage changes can be made relatively safely based on water intake, urine
glucose concentration, and clinical assessment.
Table 1. Parameters for changing insulin dosage when using
glargine or PZI in diabetic cats (adapted from Rand, JS and Marshall RD. Vet
Clinics Small Anim 2005;35, 211-224.)
|
Parameter used for dosage adjustment |
Change in dose |
|
Preinsulin BG >360 mg/dl and/or nadir >180
mg/dl |
Increase by 0.5-1.0 U |
|
Preinsulin BG 270 to <360 mg/dl and/or nadir
90-180 mg/dl |
No dose change |
|
Preinsulin BG 190-270 mg/dl and/or nadir 54-72
mg/dl |
Use nadir, water drunk, urine glucose, and next
preinsulin BG to determine whether to decrease or maintain dose |
|
Preinsulin BG <180 mg/dl and/or nadir <54
mg/dl |
Reduce dose by 0.5-1.0 U or if total dose is 0.5-1
U, stop insulin and check for diabetic remission |
|
If clinical signs of hypoglycemia are observed |
Reduce dose by 50% |
|
If water intake <20 ml/kg on canned food or
<70 ml/kg on dry food |
No dose change |
|
If water intake >40 ml/kg on canned food or
>100 ml/kg on dry food |
Increase by 0.5-1.0 U |
|
If urine glucose is >3+ |
Increase by 0.5-1.0 U |
|
If urine glucose is negative |
Reduce dose by 1 U and check for diabetic remission
if on a low insulin dose |
Determining
if Diabetic Remission has Occurred
It is suggested that insulin therapy be continued for
a minimum of 2 weeks to allow pancreatic beta cells to recover fully from
glucose toxicity. After a minimum of 2 weeks of insulin therapy, if the
preinsulin blood glucose is <200 mg/dl and the insulin dose is only 0.5-1 U
per cat once or twice a day, insulin should be withheld and a 12-hour blood
glucose curve performed. If the blood glucose concentration exceeds 200 mg/dl
at the next scheduled dosing time, administer 1 U twice daily; if the blood
glucose is 200 mg/dl or less, continue to withhold insulin and discharge with a
follow up visit in one week.
Dietary Recommendations
Correction of obesity and minimizing the impact of
the diet on postprandial blood glucose concentration are important dietary
considerations in diabetic cats. Obesity is common in the age population of
cats that are at risk for diabetes; over 40% of cats aged 9-13 in the
The central theme in studies evaluating the impact of
diet on glycemic control in diabetic cats has been restriction of carbohydrate
absorption by the gastrointestinal tract, either by inhibiting starch digestion
(acarbose), inhibiting intestinal glucose absorption (fiber), or decreasing
carbohydrate ingestion (low carbohydrate-containing diets). Intuitively, the
most effective means to minimize gastrointestinal absorption of carbohydrates
in the diabetic cat is to feed diets that contain minimal amounts of
carbohydrate and this approach has proven very effective. Current
recommendations are to feed a low carbohydrate such as Nestle Purina DM or
Hill’s m/d. The beneficial role, if any, of the high protein or high fat
content of these carbohydrate-restricted diets on control of glycemia is not
known at this time. These dietary recommendations are intended to augment and
not replace insulin therapy. If an alternative to insulin therapy is sought,
consideration should be given to an oral hypoglycemic gent and a low
carbohydrate diet. This may be a useful approach while the owner of a newly
diagnosed diabetic adjusts to the reality of giving insulin injections.
Websites that may be helpful to owners of diabetic cats include <www.veterinarypartner.com> and
<www.felinediabetes.com>.
Selected
References
Mazzaferro EM, Greco DS, Turner AS, et al. Treatment
of feline diabetes mellitus using an alpha-glucosidase inhibitor and a
low-carbohydrate diet. J Feline Med Surg 2003; 5(3), 183-9.
Rand, JS and Marshall RD. Diabetes
mellitus in cats. Vet Clinics
Small Anim 2005;35, 211-224.