Vol. 22, No.
5 May 2000
CE Refereed Peer Review
FOCAL POINT
★Therapy for diabetes mellitus is
aimed toward the underlying
abnormality; insulin is
administered when an absolute
insulin deficiency exists, and oral
hypoglycemic agents can be used
if the metabolic abnormalities of
type 2 diabetes are present.
KEY FACTS
■ Classification of cats as type 1
or type 2 diabetics is difficult; type
2 diabetes may be the more
common form.
■ The importance of dietary therapy
cannot be overemphasized.
■ Recombinant human insulin may
be the preferred type of insulin
for cats.
■ Glipizide, a sulfonylurea, has
been shown to have relatively
few adverse effects in cats, but
long-term efficacy is only
approximately 35% to 40%.
■ Oral administration of vanadium
has been shown to decrease
clinical signs in diabetic cats.
Treatment of Feline
Diabetes Mellitus:
Overview and Therapy*
Auburn University
Ellen N. Behrend, VMD, MS
Colorado State University
Deborah S. Greco, DVM, PhD
ABSTRACT: Diabetes mellitus can be particularly frustrating for veterinarians and clients.
Weight management plays a large role in diabetes control, but the recommended high-fiber
foods can be unpalatable and are associated with other adverse effects. Rotation of diets and
other solutions may help to avoid these problems. Deciding whether to use insulin or hypo-
glycemic agents can be difficult. Glipizide, vanadium, chromium, and acarbose are oral hypo-
glycemic agents that may be tried as therapy.
D
iabetes mellitus (DM) is a common endocrinopathy in older cats; an es-
timated 1 of 400 cats is affected.1 Aside from the debilitating conse-
quences of DM, management of the disorder may present a significant
problem to owners and diagnosis can be a challenge for veterinarians. Owners
may need to change their animals’ diet and give daily insulin injections or oral
hypoglycemic agents. The requirement for timely insulin injections and frequent
rechecks dictates an owner’s schedule; some owners are unable to adhere to a
rigid treatment plan or master injection technique. Although oral hypoglycemic
agents may avert the necessity of insulin injections in some diabetic cats, these
medications must still be administered twice daily.2,3 The need for regular moni-
toring and the occurrence of secondary problems can lead to frequent veterinary
visits and substantial expense. For veterinarians, features peculiar to cats can pre-
sent certain difficulties. Because of the finicky nature of some cats, compliance
with prescribed dietary regimens can be poor. Serial blood glucose measurement
to determine diabetic control can be complicated by the presence of stress hyper-
glycemia. In addition, the need for exogenous insulin in cats waxes and wanes;
this phenomenon is understandable but can be a source of frustration for both
owners and veterinarians.
DISEASE CLASSIFICATION IN HUMANS
Because the study of DM in cats is based on that in humans, comprehension
*Copyright 1998 by the Western Veterinary Conference from the booklet “Clinical Phar-
macology, Principles and Practice.” Modified with permission.
Small Animal/Exotics
of the human classification scheme is important. Hu-
man DM is classified as type 1 and type 2 and was pre-
viously known as insulin-dependent DM and non–in-
sulin-dependent DM, respectively. The two types now
denote specific pathophysiologies. Type 1 DM, com-
monly referred to as juvenile onset, is defined by an ab-
sence of insulin secondary to immune-mediated de-
struction of pancreatic islet beta cells4; overt DM results
when beta-cell function decreases to less than 20% to
25% of normal.5 Human type 2 DM occurs in older
people. Its pathophysiology is more complex and is as-
sociated with three major metabolic abnormalities that
coexist to varying degrees: impaired insulin secretion,
peripheral insulin resistance, and increased basal hepat-
ic glucose production. Type 1 diabetes is still typically
insulin dependent, but type 2 may be insulin depen-
dent or independent.4,6
The abnormal insulin secretion in type 2 DM may
be caused by altered ability of beta cells to sense blood
glucose concentrations.7 Normally, the insulin response
to a glucose or glucagon challenge occurs in two phas-
es—immediate and delayed. In the early stages of type
2 DM, after the capacity of beta cells to release insulin
has diminished by 80% to 90%, fasting hyperglycemia
is present, the immediate insulin phase is markedly re-
duced or absent, and the delayed phase occurs later
than normal and is often exaggerated.7 Because hyper-
glycemia and hyperinsulinemia coexist, the insulin re-
sponse must be considered inadequate because the
functional mission of beta cells is to secrete sufficient
insulin to maintain normoglycemia.4
Disappearance of the delayed phase occurs later in
the disease when fasting hyperglycemia supersedes the
renal threshold, resulting in glycosuria.8 Insulin resis-
tance is manifested by the need for higher-than-normal
concentrations of insulin in the blood to promote pe-
ripheral glucose uptake and suppress hepatic gluconeo-
genesis for maintenance of normoglycemia. Basal hy-
perinsulinemia and an exaggerated insulin response early
in the course of disease in type 2 DM are believed to be
a compensatory response to insulin resistance.5
Therapy of DM is generally aimed toward the under-
lying abnormality. In type 1 DM, the primary problem
is lack of insulin. Consequently, treatment provides an
exogenous source of the hormone. In type 2 DM, oral
agents can be used that attempt to diminish the under-
lying abnormalities by decreasing insulin resistance, in-
creasing insulin secretion, and/or inhibiting hepatic
glucose production. However, as type 2 DM progresses,
insulin deficiency occurs and exogenous insulin injec-
tions will be required. Because the metabolic abnormal-
ities treated by most oral hypoglycemic agents do not
occur in type 1 diabetics, administration of these medi-
TYPE 1 VS. TYPE 2 DIABETES ■ GLUCOSE INTOLERANCE ■ GLUCOSE TOXICITY
Compendium May 2000
cations is inappropriate. An exception is acarbose, which
has a role in management of both type 1 and type 2 di-
abetes.
DISEASE CLASSIFICATION IN CATS
Although knowing the type of DM can direct the
choice of therapy, distinguishing between the two types
in cats tends to be difficult. As in humans, intravenous
administration of glucose or glucagon in cats produces
immediate and delayed phases of insulin secretion, and
an abnormality in this response has been reported to
differentiate the types of primary feline DM. In a study
by O’Brien and colleagues,8 9 of 16 nondiabetic cats
were judged to be glucose intolerant on the basis of ab-
normal glucose clearance after administration of a large
dose of glucose, and the insulin response seen in three
of these cats mimicked the pattern seen in early human
type 2 DM. Insulin secretion of seven diabetic cats in
the same study8 resembled that which occurs in ad-
vanced type 2 DM in humans. However, in a study by
Kirk and colleagues,9 which used intravenous glucagon,
7 of 30 (23%) diabetic cats had insulin responses con-
sistent with type 2 DM and the remaining 23 cats
(77%) were classified with type 1 DM.
The results of Kirk and coworkers’ study9 imply that
oral hypoglycemic agents would not be helpful in most
cats, whereas the results of O’Brien and coworkers’
study8 suggest that they would. This paradox demon-
strates the difficulty in distinguishing between the two
types of DM in cats. Variation of results in intravenous
glucose tolerance tests among individual cats suggests
that glucose or glucagon tolerance test results in a single
cat must be interpreted with caution.10 Furthermore,
classifying cats on the basis of these results may be inac-
curate because of the tendency to overestimate the true
incidence of type 1 DM. Prolonged hyperglycemia in it-
self diminishes the secretory capacity of pancreatic islet
beta cells, thereby mimicking type 1 DM—an effect re-
ferred to as glucose toxicity.11 In other words, the inability
to secrete insulin, which is the basis for classifying these
cats as having type 1 DM, may actually be caused by
type 2 DM. Histologic findings consistent with type 1
DM have been observed in diabetic cats, suggesting that
this form of disease does exist.7,12,13 Although some au-
thors believe that type 2 DM is by far the more com-
mon,6 the true incidence remains unknown.
Type 2 DM is vastly more common than is type 1 DM
in humans, and oral hypoglycemic agents with or without
insulin are used for treatment. Accordingly, owners expect
the same for their cats. Although type 2 diabetes is proba-
bly also the more common form in cats, glucose toxicity
may be a more significant problem in cats because the di-
abetic state may be undetected for a longer period.14 Pa-
Compendium May 2000
tients with advanced type 2 DM and glucose toxicity, a
situation that is probable for most diabetic cats, have lost
the ability to secrete insulin and are likely to require in-
sulin therapy. Conversely, reversal of glucose toxicity may
eliminate the diabetic state in some cats.2,3,15 Control of
blood glucose may allow beta cells to regain insulin secre-
tory capacity, and therapy with insulin or oral hypo-
glycemics can be discontinued, at least temporarily.
Type 3 (secondary) DM is an uncommon form that
results from insulin resistance or beta-cell loss from an
unrelated disease process, such as hyperadrenocorticism
or acromegaly.6 Resolution of the primary disease pro-
cess also eliminates type 3 DM unless it has advanced
beyond the early stages.
THERAPY
Diet
Appropriate dietary therapy is essential for diabetic
control and should be directed at correcting obesity,
maintaining consistency in the timing and caloric content
of meals, coordinating with the physiologic effects of ad-
ministered insulin, minimizing postprandial fluctuations
in blood glucose, and preventing or managing concurrent
diseases or diabetic complications.16,17 Dry and/or canned
foods can be used. Soft, moist foods should be avoided
because they contain simple carbohydrates that are rapid-
ly absorbed from the gastrointestinal tract, resulting in a
rapid postprandial rise in blood glucose.18
Calories
Obesity and malnutrition can lead to insulin resis-
tance, and malnutrition can lead to diminished insulin
secretion.19,20 Because these effects can be reversed after
body weight abnormalities have been corrected, achiev-
ing and maintaining ideal body weight are crucial.
For maintenance, cats need 60 to 70 kcal/kg/day.17 If
a patient is overweight, caloric intake should be restrict-
ed to 70% to 75% of calculated energy needs. Under-
weight patients should be fed at the maintenance level
for ideal body weight. A high-calorie food may also be
fed on a short-term basis. Weight change should occur
gradually, and blood glucose concentrations must be
monitored throughout periods of weight gain or loss
because insulin requirements may change. Once ideal
body weight has been achieved, maintenance is initiat-
ed by feeding the amount calculated to provide mainte-
nance energy requirements. An animal’s weight should
be monitored periodically to ensure that it is stable and
caloric requirements are being met. The amount fed
can be changed accordingly.17
Fiber
The role of dietary fiber in diabetic cats is controver-
TYPE 3 DIABETES ■ POSTPRANDIAL BLOOD GLUCOSE ■ MAINTENANCE ENERGY REQUIREMENTS
Small Animal/Exotics
sial. Through unknown mechanisms, dietary fiber can
delay gastrointestinal glucose absorption, reducing
postprandial fluctuations in blood glucose and enhanc-
ing glycemic control.17,21 In humans, dietary fiber can
also decrease serum cholesterol, triglyceride concentra-
tions, and systemic blood pressure.17 One study22 showed
that insoluble fiber (i.e., the type present in commercial
high-fiber cat food) improves glycemic control in dia-
betic cats.22 Recent theories, however, suggest that high-
carbohydrate diets may lead to DM in cats and that
high protein may be beneficial.23 Certainly, high-fiber
diets are good options for weight control. The diets
that are likely to be most effective for weight loss are
those that contain the most fiber and digestible com-
plex carbohydrates on a dry-matter basis.
Complications associated with high-fiber diets are
poor palatability, increased frequency of defecation, con-
stipation and obstipation (insoluble fiber), soft stools and
diarrhea (soluble fiber), weight loss, and hypoglycemia.21
Flatulence and abdominal discomfort are noted in hu-
mans on high-fiber diets but are usually transient.17 If
firm stools, constipation, or obstipation becomes a prob-
lem, soluble fiber, such as sugar-free Metamucil® (Proc-
tor & Gamble, Cincinnati, OH), can be added to the
food.24 One teaspoon should be added once or twice dai-
ly and then titrated as needed to keep stools soft.
Lack of palatability can be problematic, and gradual-
ly switching to a high-fiber diet can preclude refusal on
the part of the patient and thus may be a useful strate-
gy. Rotating the type of high-fiber diet may avoid de-
velopment of boredom with a particular food. If high-
fiber diets are refused, soluble fiber can be added as
needed.21
Protein
How dietary protein affects glycemic control is un-
known. In human diabetics, low dietary protein is used
to minimize progression of diabetic nephropathy.
Whether this is necessary in cats or whether it would be
beneficial to feed high dietary protein to mimic the nat-
ural diet is unknown.23 Current recommendations for
cats are to feed a diet that is approximately 28% to 40%
protein on a dry-matter basis. If concurrent renal disease
exists, however, lower protein content is indicated.21
Fat
In human diabetics, low dietary fat has been shown
to both exacerbate and improve hyperlipemia, and high
dietary fat may cause insulin resistance.17,21 In canine
diabetics, alterations in synthesis of enzymes used in
lipid metabolism or in liver function usually result in
hypertriglyceridemia with less severe hypercholeste-
rolemia.25 In light of these derangements and until the
Small Animal/Exotics
results of dietary fat manipulation in cats are evaluated,
restriction of dietary fat (i.e., 17% or less of dry matter)
seems prudent.21
Concurrent Disease
Because most diabetic cats are middle aged or older,
a variety of other age-related diseases may be present,
and the diet should be modified accordingly. Pancreatic
diseases, such as pancreatitis and exocrine pancreatic in-
sufficiency (EPI), may also occur in diabetic patients;
and high dietary fiber may be detrimental in these cas-
es.12,17 If the amount of fiber being fed seems to exacer-
bate concurrent pancreatitis, it should be decreased.17
Although fiber is considered to be deleterious in cases
of EPI because of its ability to inactivate digestive en-
zymes,17,26 cellulose (the fiber most commonly found in
commercial high-fiber cat foods) did not affect purified
solutions of pancreatic enzymes in vitro.27 Successful
use of high-fiber diets in diabetic cats with EPI has
been reported.21 Human patients with EPI on high-
fiber diets experience increased flatulence.27
Feeding Schedule
In human medicine, insulin is administered with
each meal to mimic the normal physiologic response
and blood glucose is checked at the time of insulin ad-
ministration as a guide to dosing. Because this ap-
proach is not practical in veterinary medicine, at least
calories should be ingested when insulin is still present
in the circulation to avoid large increases in blood glu-
cose.21 This schedule can be accomplished by feeding
several small meals per day instead of one large meal.
Accordingly, for animals that receive insulin once a day,
three equal-sized meals at 6-hour intervals has been
suggested. Animals receiving twice-daily insulin can be
fed immediately before each insulin injection as well as
in the mid-afternoon and late evening.28
Many owners are unable to comply with these feed-
ing schedules. In these cases, animals receiving twice-
daily insulin should be fed immediately before each in-
jection.17,21,29 Animals receiving once-daily injection can
be fed one meal before treatment and a second in the
late afternoon or early evening.17
If an animal does not eat, the insulin dose can be re-
duced (usually by 50%) or skipped entirely; if anorexia
persists, the animal should be evaluated by a veterinari-
an to determine the cause.29 Animals that eat small
amounts throughout the day may most closely approxi-
mate the ideal situation because postprandial hyper-
glycemia is unlikely to be profound. Although feeding
discrete meals is preferred because it is easier to deter-
mine whether the patient is eating normally and to ad-
minister insulin accordingly, cats that are refractory to
PANCREATITIS ■ EXOCRINE PANCREATIC INSUFFICIENCY ■ ANOREXIA
Compendium May 2000
such a schedule can be fed free choice as long as daily
caloric intake stays within prescribed limits.17,21
Insulin
Mammalian insulin comprises 51 amino acids that
are arranged in two polypeptide chains, but small inter-
species differences in amino acid sequences exist. Feline
insulin is most similar to beef insulin—varying by only
one amino acid—but differs from pork and human in-
sulin by three and four amino acids, respectively.21 His-
torically, beef, pork, and human recombinant insulins
have been commercially prepared, but the availability of
animal-source insulin is decreasing. Human recombi-
nant insulin is preferred for humans, especially those
who are prone to develop allergies or immune resistance
to animal-source insulin.30 In contrast, although use of
insulin derived from another species can lead to insulin
resistance in cats, formation of a low titer of antibodies
against a foreign insulin may actually help to prolong
the duration of action, which is a desirable effect.21
Insulin Types and Syringes
There are five main forms of insulin available to vet-
erinarians: Lente® (Eli Lilly, Indianapolis, IN), Ultra-
lente® (Eli Lilly), neutral protamine Hagedorn (NPH;
also known as isophane suspension), protamine zinc in-
sulin (PZI), and regular insulins. These insulins are de-
rived from humans, cattle, and pigs and are marketed
by different companies (Table I). Regardless of the
source, these insulins can be further classified as short,
intermediate, or long acting, depending on the formu-
lation. In general, the longer acting the insulin is, the
less potent it is.21
Regular insulin is not complexed to any other mole-
cules that retard absorption and, as a result, is short act-
ing (Table II). The insulin molecule in NPH and PZI
is bound to the protein protamine to slow absorption.
Although PZI was discontinued as a human prepara-
tion in 1991, it is now available on an investigational
basis for veterinary use (Blue Ridge Pharmaceuticals,
Greensboro, NC). NPH insulin is considered to be in-
termediate acting, and PZI is long acting. Lente® in-
sulins rely on alterations in zinc content and the size of
zinc–insulin crystals to alter the subcutaneous absorp-
tion rate.21 Lente® insulin is intermediate acting and
consists of 30% regular and 70% Ultralente® insulin.21
Ultralente® insulin is microcrystalline and long acting.
Insulin preparations that consist of NPH and regular
insulin are also available.
Although there is a system for naming insulin, the
nomenclature can be confusing because manufacturers
use different brand names even though the preparations
may be from the same species and have the same dura-
Compendium May 2000 Small Animal/Exotics

tion of action. In general, the name of an insulin iden- the insulin concentration with the correct syringe is es-
tifies both its source and type; the source of the insulin sential to ensure accurate dosing.
is identified by a letter (R for regular, L for Lente®, N Insulin syringes are packaged with a fine 26- or 27-
for NPH, and U for Ultralente®) or is spelled out. For gauge needle to minimize discomfort on injection. The
example, Humulin ® L (Eli Lilly) and Novolin ® L U40 and U100 syringes are available in 1-ml sizes.
(Novo Nordisk, Princeton, NJ) are both recombinant U100 syringes are also manufactured in low-dose sizes
human Lente® insulins.29 Lente® Iletin® I (Eli Lilly) is (0.3 and 0.5 ml) designed to accurately draw a small
beef/pork insulin, and Lente® Iletin® II (Eli Lilly) is dose of insulin without the need for dilution. These sy-
pork insulin. Lente® Iletin® II and Humulin® L are ringes help achieve accurate dosing when small quanti-
both Lente® insulins but are derived from different ties are required and are especially recommended in
species. One exception is Velosulin® (Novo Nordisk), cats. They may also be particularly helpful for elderly
which is a regular human insulin. pet owners because the unit marks are easier to read.29
Insulin is available in 40-, 100-, and 500-U/ml con- Insulin can be diluted when extremely small doses or
centrations, designated U40, U100, and U500, respec- fractional increments (0.5 or 0.25 U) are needed. Be-
tively. In the United States, U100 is the primary concen- cause of the difficulty involved in giving small doses, ad-
tration available, and 1 U of insulin is approximately ministration of less than 2.0 U of undiluted U100 in-
equivalent to 36 µg.31 Insulin syringes are specifically sulin results in marked overdose in diabetic children in
manufactured to be used with one concentration of insulin up to 95% of cases.32 A diluent specifically designed by
and are designated U40 or U100 accordingly. Matching the manufacturer for a given insulin preparation should
be used, and special care must
TABLE I be taken to ensure that the
Insulin Preparations29,a correct dose of diluted insulin
is administered with an insulin
Species of syringe. For example, if a 1:10
Product (Manufacturer) Type Origin Concentration dilution of insulin is prepared,
Short acting the new concentration is 10
Humulin® R Regular Human U100 U/ml and a full 1-ml U100
(Eli Lilly, Indianapolis, IN) syringe contains only 10 U.
Novolin® R Regular Human U100 Similarly, a full 0.5-ml syringe
(Novo Nordisk, Princeton, NJ) contains 5 U and a full 0.3-ml
Velosulin® BR (Novo Nordisk) Regular Human U100 syringe contains 3 U.31
Intermediate acting
Humulin® L (Eli Lilly) Lente® Human U100 Dose Regimens
Humulin® N (Eli Lilly) NPH Human U100 The dose of insulin admin-
Novolin® L (Novo Nordisk) Lente® Human U100 istered depends on whether
Novolin® N (Novo Nordisk) NPH Human U100 Lente®, NPH, Ultralente®, or
PZI insulin is used (Table III).
Long acting Dosing should be conserva-
Protamine zinc insulin Protamine Beef, pork U40 tive, with increments increased
(Blue Ridge Pharmaceuticals, zinc based on resolution of clinical
Greensboro, NC) signs, urine glucose monitor-
Humulin® U (Eli Lilly) Ultralente® Human U100 ing, and serial measurement of
Mixtures
blood glucose.29 Intermediate-
Humulin® 50/50 (Eli Lilly) 50% NPH, Human U100 acting insulins (e.g., NPH), tend
50% regular to be more bioavailable than
Humulin® 70/30 (Eli Lilly) 70% NPH, Human U100 are longer-acting insulins; thus
30% regular an injection of NPH achieves
Novolin® 70/30 70% NPH, Human U100 a higher serum insulin con-
(Novo Nordisk) 30% regular centration more rapidly and
aModified from Greco DS, Broussard JD, Peterson ME: Insulin therapy. Vet Clin North Am Small
the starting dose is lower. Be-
cause absorption of long-act-
Anim Pract 25:675, 1995; with permission.
BR = buffered regular; NPH = neutral protamine Hagedorn. ing insulins varies greatly among
cats,33,34 these dose recommen-

SYRINGE TYPES ■ INSULIN CONCENTRATION ■ DILUENTS

Small Animal/Exotics Compendium May 2000

TABLE II
Characteristics of the Insulin Types3
Time to
Route of Duration of Maximum Duration of
Insulin Type Administration Action Onset Effect (hr) Effect (hr)
Regular Subcutaneous Short 10–30 min 1–5 4–10
Lente® (Eli Lilly,
Indianapolis, IN) Subcutaneous Intermediate <1 hr 2–8 6–14
Neutral protamine Hagedorn Subcutaneous Intermediate 0.5–3 hr 2–8 4–12
Protamine zinc insulin Subcutaneous Long 1–4 hr 3–12 6–24
®
Ultralente (Eli Lilly) Subcutaneous Long 1–8 hr 4–16 8–24

TABLE III
Initial Insulin Regimens for Diabetic Cats29,a
Initial Dose Insulin Adjustment
Insulin Type (U) Dosing Frequency Feeding Schedule (U/dose)
Lente® (Eli Lilly, 2–3 Twice daily Twice dailyb or free choice 0.5–1
Indianapolis, IN)
Neutral protamine Hagedorn 1 Twice daily Twice dailyb or free choice 0.5–1
Protamine zinc 1–3 Once or twice dailyc Twice dailyb or free choice 0.5–1
Ultralente® (Eli Lilly) 1–3 Once or twice dailyc Twice dailyb or free choice 0.5–1
aModified from Greco DS, Broussard JD, Peterson ME: Insulin therapy. Vet Clin North Am Small Anim Pract 25:684, 1995; with per-
mission.
b Preferred.
c Therapy can be instituted once daily; twice-daily therapy may ultimately be required.

dations are offered only as guidelines. The correct dose
needs to be determined individually.
Ultralente® insulin, which is available as a human re-
combinant product, may be used initially.35 If Ultra-
lente® insulin is used, treatment should begin with
once-daily administration but can be increased to twice
daily if blood glucose testing suggests an inadequate
duration of action. However, in approximately 20% of
diabetic cats, Ultralente® insulin does not adequately
control blood glucose levels, which tend to remain
above 300 mg/dl for most of the day with resultant
polyuria and polydipsia.21,35 For these cats, Lente® in-
sulin is often a better choice for glycemic control.36,37
When diabetic patients are in transition from com-
plicated diabetes and ketoacidosis to maintenance ther-
apy, the decision to change from short-acting (i.e., reg-
ular) to intermediate- or long-acting insulin should be
made on the basis of resolution of ketosis and clinical
signs. The transition from hospital to home mainte-
nance therapy can be made by using a low dose (1 to 2
U) of regular insulin combined with intermediate- or
long-acting insulin at the recommended maintenance
doses.29
Mixtures
In human diabetics, insulins can be combined to
fine-tune glucose regulation.38–40 Lente® insulin is al-
ready a combined form, and stable premixed 70%
NPH–30% regular and 50% NPH–50% regular in-
sulins are also available (Table I). Intermediate- or long-
acting insulins supply a basal insulin serum concentra-
tion for an extended period, whereas regular insulin
mimics the increased insulin concentrations during and
immediately after consumption of a meal and thus
minimizes postprandial hyperglycemia. In veterinary
medicine, meticulous glucose control is seldom neces-
sary. Furthermore, the typically short duration of action
(less than 8 hours) of premixed NPH and regular in-
sulin causes a rapid decrease in blood glucose and is of-
ten associated with hypoglycemic episodes; thus they
are seldom indicated.
Despite their shortcomings, insulin combinations

INITIAL INSULIN DOSING ■ TRANSITION DOSES

Compendium May 2000
may be useful in three situations: to manage patients
with insulin resistance, manage those with a tendency
toward ketoacidosis,41,42 and facilitate administration of
insulin to an animal for which once-daily insulin is in-
adequate and whose owner is unwilling or unable to
administer insulin twice daily.29 For patients in the last
category, a combination of intermediate- and long-act-
ing insulins may be given in the morning after a meal
that accounts for two thirds of the daily caloric require-
ment. The long-acting insulin dose should be 0.5 to
0.7 U/kg, and the intermediate-acting insulin should
be one third of the long-acting insulin dose. The ani-
mal should be given a meal that meets the remainder of
the daily caloric requirements 8 to 10 hours later. Good
success has been achieved in regulating dogs with this
regimen.29 The best combination may be Lente® and
Ultralente® insulins because they can be mixed in one
syringe and given as a single injection. Some other
types of insulin should not be combined in a single sy-
ringe. In such cases, two separate injections can be given.
Injection Location and Technique
and Client Education
The site and method of insulin injection are important
aspects of client education. An appropriate location for
an injection site must be chosen because absorption of
insulin from various sites in the body differs. For exam-
ple, in humans, insulin absorption is more rapid from
the abdomen than from the thigh, and injection into an
extremity may result in inconsistent insulin absorption,
depending on exercise and limb movement.39 In cats, the
dorsal neck or scruff has commonly been used but may
not be ideal because of low blood flow and increased fi-
brosis caused by repeated injections. A better option may
be to administer insulin at sites along the lateral ab-
domen and thorax. The chosen area should be rotated
daily to prevent injection-site fibrosis.29
Owners should be instructed to begin the injection
process by removing the insulin bottle from the refrig-
erator and mixing the contents by gentle rolling or agi-
tation. The insulin bottle should then be turned upside
down and the correct amount of insulin drawn into an
appropriate insulin syringe. The client should be given
precise directions on technique. One common mistake
is measuring the dose of insulin from the bottom,
rather than the top, of the plunger.
To detect and avoid all errors, owners should practice
by using saline under the observation of a veterinarian
or veterinary technician. Clients should be instructed
to inject insulin in their pets by lifting the loose skin
over the lateral abdomen or thorax and inserting the
needle at a 45˚ angle to the skin along the long axis of
the skinfold. If it is inserted perpendicular to the skin-
INSULIN COMBINATIONS ■ INJECTION SITE ■ SULFONYLUREAS
Small Animal/Exotics
fold, the needle may penetrate the other side of the skin
and deposit the insulin on the hair. Clipping or shaving
a 2 × 2–inch square on the lateral thorax or abdomen
can assist owners in accurate needle placement.29
At least 30 minutes should be set aside to instruct
owners on proper technique. It often helps to reinforce
a verbal discussion with written instructions to which
owners can refer. Many commercially available pam-
phlets provide information on injection techniques,
feeding, and management of hypoglycemic episodes
along with formatted log sheets for owners to record
food intake, clinical signs, urine glucose measurements,
and insulin doses.
Oral Hypoglycemic Agents
Oral hypoglycemic agents include the sulfonylureas
(glipizide, glyburide, glimepiride), biguanides (met-
formin), thiazolidinediones (troglitazone), α-glucosi-
dase inhibitors (acarbose), and transition metals (vana-
dium, chromium). These medications are the mainstay
of therapy for humans with type 2 diabetes because
they improve insulin sensitivity, increase insulin secre-
tory response to glucose, and/or decrease hepatic glu-
cose production. In other words, these agents correct
the major metabolic derangements of type 2 DM.43
Although type 2 DM is likely the more common
form of the disorder in cats, sulfonylureas have had
limited success for several possible reasons. First, al-
though both humans and cats with type 2 diabetes have
deposition of amyloid in pancreatic islet beta cells, the
extent of deposition is greater in cats and involves ap-
proximately 80% of the pancreatic islet beta cells com-
pared with approximately 30% in humans.14 Conse-
quently, cats reserve less insulin, and such agents as
glipizide, which act to increase insulin release, are less
effective. Second, glucose toxicity may be more pro-
found in cats. Thus ketosis is more common in feline
diabetics than in humans, and this is probably a reflec-
tion of the greater suppression of insulin secretion by
glucose toxicity and/or loss of beta cells through amy-
loid deposition.14 Third, limited success may simply re-
sult from lack of experience. Glipizide is the only oral
hypoglycemic agent that has undergone clinical trials in
cats. Perhaps other agents that have different mecha-
nisms of action (e.g., targeting hepatic glucose synthesis
or insulin resistance) may be more effective.
Agents That Promote Insulin
Release from the Pancreas
The primary action of sulfonylureas is to increase
beta-cell insulin release and augment beta-cell respon-
siveness to glucose.44 Secondary effects include suppres-
sion of hepatic glucose production and increased in-
Small Animal/Exotics
sulin sensitivity. These effects may occur as a direct re-
sult of sulfonylurea action or as an indirect result of the
better glycemic control and reduction of glucose toxici-
ty induced by the sulfonylurea.45
Nelson and colleagues2 conducted a preliminary study
of 20 diabetic cats treated for 12 weeks with oral glip-
izide (5 mg twice daily), a second-generation sulfonyl-
urea. Thirteen cats (65%) initially had a complete or
partial response, whereas the other seven (35%) did not
respond. In one cat that responded completely and an-
other that responded partially, glipizide became ineffec-
tive over time (6 and 9 months, respectively), suggesting
a long-term response rate of 55%.2 A more recent inten-
sive study3 of 50 cats treated similarly showed less suc-
cess. Of the 50 cats, 7 (14%) responded completely, 6
(12%) were judged to be transient diabetics, and 28
(56%) did not respond. Treatment in six cats (12%) was
considered to have failed on the basis of serial blood glu-
cose measurement, but owner opinion and other labora-
tory evidence supported the belief that the cats’ condi-
tion had improved. (These cats would have been
considered partial responders in the study by Nelson and
colleagues.2) The remaining three cats (6%) responded
initially to glipizide, but glycemic control deteriorated
over time. Thus the long-term success rate was 38% if
the cats with transient diabetes are counted as successes.3
Likewise, a recent retrospective study of 104 cats report-
ed successful glipizide therapy in approximately 35%.12
Which cats will respond to glipizide cannot be pre-
dicted. Because glipizide acts by increasing insulin re-
lease, insulin must be present within the beta cells for
the agent to be effective. The ability to secrete insulin,
however, cannot be consistently demonstrated because
of glucose toxicity. In the study by Nelson and
coworkers,2 19 of 20 cats had little or no increase in
serum insulin after intravenous glucagon administra-
tion; furthermore, no difference existed between cats
that responded completely, partially, or not at all in
terms of baseline serum insulin concentration, insulin
peak response, and total insulin secretion.
Adverse effects related to glipizide administration seem
to be minimal and, in most cases, transient. Vomiting,
the most common effect, was noted in approximately
15% of cats.2,3 In the study by Nelson and coworkers,2
vomiting occurred within 30 minutes of drug adminis-
tration during the first week of treatment and ceased af-
ter 3 to 5 days in two cats despite ongoing treatment. In
another study,3 the medication was discontinued and
vomiting resolved within 5 days; therapy was restarted
(using a gradually increasing regimen) without recur-
rence of vomiting in most cats. Two cats had persistent
vomiting that necessitated discontinuation of the medi-
cation.2,3
ORAL GLIPIZIDE ■ ADVERSE EFFECTS ■ HEPATIC ABNORMALITIES
Compendium May 2000
In the study by Nelson and coworkers,2 two cats had
mild increase in serum alanine aminotransferase activi-
ty, one had mild increase in serum alkaline phosphatase
activity, and one had mild increase in serum cholesterol
concentration. In two of three cats, glipizide was con-
tinued despite the biochemical changes,2 and whether
these alterations resolved was not clear. Approximately
10% of cats developed increased liver enzymes and
clinical icterus within 4 weeks after therapy was initiat-
ed.3,12 Icterus resolved within 5 days of cessation of
drug administration; although hepatic abnormalities
typically did not recur after therapy was restarted with
gradually increasing doses,3 they have been shown to do
so.46 Hypoglycemia has been noted in approximately
12% to 15% of cats that respond to glipizide.2,3 In
these cats, DM had resolved, at least temporarily, and
glipizide was discontinued.
Most cats that respond without continued adverse ef-
fects can be treated with glipizide for life; some cats
have been treated for longer than 7 years.21 However,
glipizide loses its effectiveness in 5% to 10% of pa-
tients.2,3 This estimate may be conservative; studies con-
ducted with longer follow-up periods may show a high-
er failure rate over time. The period from initiation of
glipizide therapy to the need for insulin therapy is un-
predictable and quite variable, ranging from a few
weeks to more than 3 years. Presumably, development
of insulin dependence is related to progressive loss of
beta cells and insulin secretory capacity.21
The ideal patient for treatment with glipizide and di-
etary therapy is stable, nonketotic, and of optimum
body weight to obese and has mild clinical signs and no
complicating diseases. Conversely, patients that are
emaciated, dehydrated, or debilitated; have recently lost
10% or more of their body weight; or have abnormali-
ties that cannot be attributed to uncomplicated, un-
treated diabetes are not good candidates.46 Although
ketoacidosis is usually considered a contraindica-
tion,12,21,46 two ketonuric cats treated with glipizide did
respond.2 Glipizide should certainly be tried in cats
whose owners refuse to give injections. In the study on
glipizide using 50 cats,3 25 of 27 owners who initially
refused to administer insulin agreed to do so later when
glipizide therapy failed; the process of developing a bet-
ter understanding of DM may have allowed these own-
ers to reconsider their decision.
Glipizide treatment should be instituted at 2.5 mg
orally twice a day with food, and cats should be exam-
ined after 1 and 2 weeks. A history; complete physical
examination; and measurement of body weight, pre-
prandial blood glucose concentration, and glucose and
ketones in urine should be done. If no problems occur
during the first 2 weeks but the diabetes is not con-
Compendium May 2000
trolled, the glipizide dose should be increased to 5.0 mg
twice daily. If ketonuria is found, the medication should
be discontinued and insulin therapy initiated.21 If vom-
iting or icterus is present, the drug should be discontin-
ued for at least 5 days or until the problem resolves.
Most cats tolerate the medication if it is started at a
lower dose and gradually increased. A dose of 1.25
mg/day should be administered for 7 days, then in-
creased, if indicated, to 2.5 mg/day for 7 days, then 2.5
mg twice daily for 14 days, and then 5.0 mg twice dai-
ly.3 If hepatic enzyme elevation or icterus occurred dur-
ing the first administration, liver enzymes and serum
bilirubin concentration should be checked periodically
after reinitiating therapy. If vomiting, hepatic enzyme
elevation, or icterus recurs, drug administration should
be stopped and the cat treated with insulin.21
After the full dose of 5 mg twice daily has been ad-
ministered for 2 weeks, the previously mentioned clini-
cal parameters and, ideally, measurement of serum glu-
cose concentrations every 1 to 2 hours from 8 AM to 6
PM should be checked every 4 weeks to monitor for
therapeutic response and adverse effects.21 Response to
therapy is evidenced by resolution of clinical signs,
blood glucose concentrations of 200 mg/dl or less, and
lack of glycosuria.46 Some evidence suggests that a pre-
prandial blood glucose concentration lower than 200
mg/dl may also indicate control.3 Use of a single sample
can be tried, but serial measurement should be done if
there is suspicion about the level of control. Because
the time until response is noted varies, the full dose reg-
imen should be administered for 12 weeks unless a
contraindication (e.g., ketonuria, deterioration of
health) arises21 (Figure 1).
If no response occurs after 12 weeks (i.e., if blood
glucose concentrations are consistently above 300 mg/dl,
weight loss occurs, and clinical signs continue), glip-
izide administration should be stopped and insulin
therapy instituted. Conversely, if clinical signs and gly-
cosuria resolve and blood glucose concentrations are
200 mg/dl or less, glipizide therapy may be tapered or
stopped; the serum glucose concentration should be
reevaluated in 1 week.21,46 If hyperglycemia is present at
the recheck, glipizide therapy should be reinitiated at
50% of the previous dose.46 If normoglycemia is pres-
ent, appropriate dietary therapy for diabetic patients
should be continued. Glipizide can be used when hy-
perglycemia recurs, but normoglycemia may be main-
tained for 12 to 14 months or longer.2 The patient should
be rechecked with a preprandial glucose concentration
or serial blood glucose measurements, as necessary, ev-
ery 3 months to document ongoing control.
Cats that have resolution of clinical signs, stable body
weight, and normal physical examinations but whose
KETONURIA ■ MONITORING ■ GLYCOSYLATED HEMOGLOBIN ■ ACARBOSE
Small Animal/Exotics
preprandial or serial blood glucose measurements are
200 mg/dl or higher present a clinical dilemma about
whether glipizide should be continued. This situation is
often caused by a partial response to glipizide; cats with
more advanced loss of pancreatic beta cells may not be
able to produce sufficient insulin to become normo-
glycemic but may have enough to reduce the mean
serum glucose concentration and partially control clini-
cal signs.2 Alternatively, the hyperglycemia noted dur-
ing serial glucose measurement may simply be a stress
response.
In one study,3 physical examination findings and gly-
cosylated hemoglobin (GHb) measurement showed
that cats fitting this description had adequate glycemic
control at home. These cats should ideally be moni-
tored by serum GHb or fructosamine concentrations to
determine overall glycemic control. If these tests are not
available, urine glucose can be monitored at home
when the cat is not stressed. If glycosuria is absent or
GHb or fructosamine concentrations are normal, glip-
izide therapy can proceed. If glycosuria is present or
glycated protein levels are elevated, insulin therapy
should be used instead.3,21
Glyburide is also a second-generation sulfonylurea.
Experience with this drug in veterinary medicine is lim-
ited. Although reportedly similar to glipizide in terms
of net glycemic control, a few qualitative differences
may exist, and glyburide has a longer duration of ac-
tion.21 Glyburide may be used at an initial dose of
0.625 mg (one half of a 1.25-mg tablet) once daily if
glipizide is not available. Response to therapy and ad-
verse reactions to glyburide are likely to be similar to
those described for glipizide.21
Agents That Inhibit Intestinal Glucose Absorption
α-Glucosidase inhibitors impair intestinal glucose
absorption by decreasing fiber digestion and hence glu-
cose production from food sources. In humans, acar-
bose is used as initial therapy in obese prediabetic pa-
tients with insulin resistance or as adjunct therapy to
enhance the hypoglycemic effects of sulfonylureas or
biguanides in patients with type 2 diabetes. Acarbose is
not indicated in humans with low or normal body
weight because of its effects on nutrition.
In cats, acarbose may be administered at a dose of
12.5 to 25 mg with meals. Side effects are more com-
mon with higher doses and include flatulence, semi-
formed stools, and in some cases overt diarrhea. The
glucose-lowering effect of acarbose alone is mild, with
blood glucose concentrations decreasing only to the
250 to 300 mg/dl range. However, one of the authors
(DSG) has noted that acarbose is an excellent adjunct
to insulin for improving glycemic control.
Small Animal/Exotics Compendium May 2000

Start glipizide therapy at 2.5 mg twice daily administered with food

At end of weeks 1 and 2, perform a physical examination,

conduct a urinalysis, and measure blood glucose concentration

If the cat is If the cat is doing well, increase glipizide If the cat is vomiting or icteric,
ketonuric, switch to 5 mg twice daily; after 2 weeks, monitor discontinue glipizide for 5
to insulin as before and measure blood glucose days or until problem resolves

Restart glipizide therapy at a lower

If no response after 12
dose, and increase gradually (see text)
weeks, switch to insulin
Achieve a dose of 5 mg twice daily
If partial response
occurs, reasons may
vary (see text) If clinical response is good,
discontinue glipizide to determine if If vomiting or icterus recurs,
therapy can be stopped (see text) switch to insulin

Figure 1—Treatment protocol for glipizide.

Agents That Improve Peripheral
Insulin Sensitivity
Transition Metals. The transition metal vanadium is
the only other oral hypoglycemic agent for which pub-
lished studies in cats are available. Indeed, transition
metals were used to treat DM in humans before the
discovery of insulin, and their use has received renewed
interest. Compounds containing vanadium have been
shown to have insulin-mimetic properties in numerous
rodent models of types 1 and 2 DM.47–49 In type 2 DM,
vanadium, by working at a postreceptor site indepen-
dent of insulin, leads to constant suppression of blood
glucose compared with the fluctuating serum glucose
levels that characterize insulin injections.47,48
One study50 assessed the toxicity of three forms of
vanadium—orthovanadate, bis(maltolato)oxovanadi-
um, and glycine-glycine vanadate—in six healthy cats.
Each form was added to drinking water for a 4-week
course with a 2-week wash-out period in between. All
six cats received all three forms of vanadium during the
course of the study. Occasional vomiting and/or diar-
rhea was noted in two of the cats, and water consump-
tion decreased substantially. No biochemical or hema-
tologic evidence of toxicity was observed. One diabetic
cat was also given orthovanadate in drinking water for
4 weeks; during this period, blood glucose decreased
and clinical signs resolved without occurrence of hypo-
glycemia.50
One author (DSG)53 has noted that low doses (0.2
mg/kg/day) of oral vanadium decrease blood glucose
and alleviate the clinical signs of DM in cats with early
type 2 DM, similar to previous findings in rodent mo-
dels.47,49,51,52 Compared with the placebo group, cats fed
vanadium in water or food gained weight, showed a
significant decrease in serum fructosamine, and had
amelioration of clinical signs.53 The placebo group lost
weight (1 kg) and had progression of clinical signs and
significantly higher serum fructosamine concentrations
at the end of the study.53 Vanadium-treated cats had
posttreatment serum fructosamine concentrations of
484 µmol/L compared with 564 µmol/L in the placebo
group (normal, below 360 µmol/L).53
These results are similar to those of another study54
in which the median serum fructosamine concentration
in well-regulated diabetic cats treated with insulin alone
was 450 µmol/L and the median serum fructosamine in
nontreated diabetic cats was 624 µmol/L. Vanadium is
available commercially (SuperVanadyl Fuel, Twin Labo-

VANADIUM ■ TOXICITY ■ SERUM FRUCTOSAMINE

Small Animal/Exotics
ratories, Inc., Ronkonkoma, NY) and can be given as a
half capsule once daily with food. Alternatively, chro-
mium may be administered at a dose of 200 µg once
daily as a tablet or capsule.
Thiazolidinediones. A new class of oral hypoglycem-
ic agents in human medicine are the thiazolidinedione
compounds.55 The mechanism of action of these drugs
may relate to interaction with a member of a family of
nuclear receptors called peroxisome proliferator-activated
receptors (PPARs), most likely PPARγ.43,55 Thiazolidine-
diones facilitate insulin-dependent glucose disposal and
inhibit hepatic glucose output by attenuation of gluco-
neogenesis and glycogenolysis.
Some authors have suggested that use of troglitazone,
a first-generation thiazolidinedione, early in the course
of type 2 DM may slow its progression.55,56 Side effects
of troglitazone in humans are usually minor, and no hy-
poglycemic reactions have been described. However, id-
iosyncratic hepatic toxicity has been observed.a Improve-
ment in fasting blood glucose, glycosylated hemoglobin,
and diabetic complications were noted in all human dia-
betics and were significant when compared with the
placebo.56,57 One author (DSG) has used 200 mg of
troglitazone once daily in cats without observing signifi-
cant changes in blood glucose regulation or side effects.
Agents That Suppress Hepatic Glucose Output
Although the exact mechanism is unknown, bi-
guanides (metformin) work mainly by inhibiting hepa-
tic glucose release and improving peripheral insulin
sensitivity. Other actions may include increased periph-
eral glucose uptake and delayed gastrointestinal glucose
absorption.43,59 No published information on their use
in diabetic cats exists.
Combining Oral Hypoglycemics with Insulin
Agents that impair glucose absorption from the intes-
tine (acarbose) or increase insulin sensitivity (vanadi-
um, metformin, troglitazone) may be combined with
insulin to improve glucose control in patients with type
2 diabetes. For cases of “brittle” diabetes, in which
small incremental changes in the dose of insulin may
precipitate hypoglycemia, addition of a drug that en-
hances the action of insulin may lead to a reduced in-
sulin requirement for attainment of normoglycemia.
In humans with type 2 diabetes, acarbose and met-
formin are commonly used in conjunction with insulin
and other oral hypoglycemic agents that cause insulin
release (sulfonylureas). Combining any oral hypo-
glycemic agent, particularly sulfonylureas, with insulin
a
Editor’s note: In March 2000, the FDA withdrew troglitazone
from the market after reports of its association with rare cases
of fatal liver failure and liver failure requiring transplantation.
TROGLITAZONE ■ BIGUANIDES ■ OWNER ASSESSMENT
Compendium May 2000
must be done cautiously because such combinations
may induce hypoglycemic reactions. Changes from in-
sulin to oral hypoglycemic agents or vice versa may be
necessary in some diabetic cats. If a cat is particularly
sensitive to insulin, changing to an oral hypoglycemic
agent should be considered. On the other hand, if the
cat is being managed with oral hypoglycemic agents
and ketosis develops, oral medication should be discon-
tinued and the cat should be treated with insulin.
PROGNOSIS
The prognosis for cats with DM is relatively good.
Not all cats respond to all types of insulin, but fair to
good control can be achieved in most feline DM pa-
tients.12 Interestingly, assessment of control by blood
glucose measurement versus owner observation did not
correlate in 54 cats in a study by Goossens and col-
leagues.12 The investigators considered mean blood glu-
cose levels of 200 to 300 mg/dl to indicate average
glycemic control, but owner-assessed clinical status was
good in most cats that had a mean blood glucose level
of less than 300 mg/dl.12 Studies by Goossens12 and
Krauss59 and their coworkers showed that cats survived
a median of approximately 17 months from the time of
diagnosis; median follow-up time was 2012 and 3559
months, respectively. The difference between the two
may be caused by the timing of data assessment rather
than a true difference in the populations.
Death may be highest during the first year—62% in
one study—and may result from diabetes or unrelated
diseases.59 The level of glycemic control may affect sur-
vival because the difference in survival times between
cats with good or average glycemic control and cats
with poor glycemic control approached statistical sig-
nificance (P = .06).12 Similarly, cats that are not insulin
dependent (i.e., their disease is controlled with oral hy-
poglycemic agents) and cats that are transiently diabetic
also tend to have a better prognosis.59
REFERENCES
1. Panciera DL, Thomas CB, Eicker SW, et al: Epizootiologic
patterns of diabetes mellitus in cats: 333 cases (1980–1986).
JAVMA 197:1504–1508, 1990.
2. Nelson RW, Feldman EC, Ford SL, et al: Effect of an orally
administered sulfonylurea, glipizide, for treatment of dia-
betes mellitus in cats. JAVMA 203:821–827, 1993.
3. Feldman EC, Nelson RW, Feldman MS: Intensive 50-week
evaluation of glipizide administration in 50 cats with previ-
ously untreated diabetes mellitus. JAVMA 210:772–777,
1997.
4. Unger RH, Foster DW: Diabetes mellitus, in Wilson JD,
Foster DW (eds): Williams Textbook of Endocrinology, ed 3.
Philadelphia, WB Saunders Co, 1992, pp 1255–1334.
5. Porte Jr D: β cells in type II diabetes mellitus. Diabetes 40:
166–180, 1991.
Compendium May 2000
6. Lutz TA, Rand JS: Pathogenesis of feline diabetes mellitus.
Vet Clin North Am Small Anim Pract 25:527–552, 1995.
7. Lutz TA, Rand JS: A review of new developments in type 2
diabetes in human beings and cats. Br Vet J 149:527–536,
1993.
8. O’Brien TD, Hayden DW, Johnson KH, et al: High dose
intravenous glucose tolerance test and serum insulin and
glucagon levels in diabetic and non-diabetic cats: Relation-
ships to insular amyloidosis. Vet Pathol 22:250–261, 1985.
9. Kirk CA, Feldman EC, Nelson RW: Diagnosis of naturally
acquired type-I and type-II diabetes mellitus in cats. Am J
Vet Res 54:463–467, 1993.
10. Sparkes AH, Adams DT, Cripps PJ: Inter- and intraindivid-
ual variability of the response to intravenous glucose toler-
ance testing in cats. Am J Vet Res 57:1294–1298, 1996.
11. Link KR, Rand JS: Glucose toxicity in cats (Abstr). J Vet In-
tern Med 10:185, 1996.
12. Goossens M, Nelson RW, Feldman EC, et al: Response to
insulin treatment and survival in 104 cats with diabetes mel-
litus (1985–1995). J Vet Intern Med 12:1–6, 1998.
13. Hall DG, Kelley LC, Gray ML, et al: Lymphocytic inflam-
mation of pancreatic islets in a diabetic cat. J Vet Diagn Invest
9:98–100, 1997.
14. Rand JS: Understanding feline diabetes. Proc 14th ACVIM
Forum:82–83,1996.
15. Nelson RW, Griffey FM, Feldman EC, Ford SL: Transient
clinical diabetes mellitus in cats: 10 cases (1989–1991). J Vet
Intern Med 13:28–35, 1999.
16. Nelson RW, Lewis LD: Nutritional management of diabetes
mellitus. Semin Vet Med Surg 5:178–186, 1990.
17. Ihle SL: Nutritional therapy for diabetes mellitus. Vet Clin
North Am Small Anim Pract 25:585–597, 1995.
18. Holste LC, Nelson RW, Feldman EC: Effect of dry, soft
moist, and canned dog foods on postprandial blood glucose
and insulin concentrations in healthy dogs. Am J Vet Res
50:984–989, 1989.
19. Nelson RW, Himsel CA, Feldman EC, et al: Glucose toler-
ance and insulin response in normal-weight and obese cats.
Am J Vet Res 51:1357–1362, 1990.
20. Biourge V, Nelson RW, Feldman EC: Effect of weight gain
and subsequent weight loss on glucose tolerance and insulin
response in healthy cats. J Vet Intern Med 11:86–91, 1997.
21. Feldman EC, Nelson RW: Diabetes mellitus, in Canine and
Feline Endocrinology and Reproduction. Philadelphia, WB
Saunders Co, 1996, pp 339–391.
22. Nelson RW, Scott-Moncrieff C, DeVries S: Dietary insolu-
ble fiber and glycemic control of diabetic cats (Abstr). J Vet
Intern Med 8:165, 1994.
23. Rand JS: Pathogenesis of feline diabetes, in Reinhart GA,
Carey DP (eds): Iams Nutr Symp Proc:83–95, 1998.
24. Nelson RW, Ihle SL, Lewis LD: Effects of dietary fiber sup-
plementation on glycemic control in dogs with alloxan-in-
duced diabetes mellitus. Am J Vet Res 52:2060–2066, 1991.
25. Zerbe CA: Canine hyperlipemias, in Kirk RW (ed): Current
Veterinary Therapy IX. Philadelphia, WB Saunders Co, 1986,
pp 1045–1053.
26. Remillard RL, Matz ME, Shell LG: Nutritional manage-
ment of complicated cases of canine diabetes mellitus. Com-
pend Contin Educ Pract Vet 14(2):176–183, 1992.
27. Dutta SK, Hlasko J: Dietary fiber in pancreatic disease: Ef-
fect of high fiber diet on fat malabsorption in pancreatic in-
sufficiency and in vitro study of the interaction of dietary
fibers with pancreatic enzymes. Am J Clin Nutr 41:517–525,
Small Animal/Exotics
1985.
28. Nelson RW: Dietary therapy for diabetes mellitus. Compend
Contin Educ Pract Vet 10(12):1387–1392, 1988.
29. Greco DS, Broussard JD, Peterson ME: Insulin therapy. Vet
Clin North Am Small Anim Pract 25:677–689, 1995.
30. Scherthaner G: Immunogenicity and allergenic potential of
animal and human insulins. Diabetes Care 16:155–165,
1983.
31. Peterson ME: Insulin and insulin syringes, in Kirk RW,
Bonagura JD (eds): Kirk’s Current Veterinary Therapy XI.
Small Anim Practice. Philadelphia, WB Saunders Co, 1992,
pp 356–358.
32. Casella SJ, Mongilio MK, Plotnick LP: Accuracy and preci-
sion of low-dose insulin administration. Pediatrics 91:1155–
1157, 1993.
33. Wallace MS, Peterson ME, Nichols CE: Absorption kinetics
of regular, isophane and protamine zinc insulin in normal
cats. Domest Anim Endocrinol 7:509–516, 1990.
34. Broussard JD, Peterson ME: Comparison of two Ultralente
insulin preparations with protamine zinc insulin in clinically
normal cats. Am J Vet Res 55:127–131, 1994.
35. Nelson RW, Feldman EC, DeVries S: Use of Ultralente in-
sulin in cats with diabetes mellitus. JAVMA 200:1828–1829,
1992.
36. Bertoy EH, Nelson RW, Feldman EC: Effect of Lente in-
sulin for treatment of diabetes mellitus in 12 cats. JAVMA
206:1729–1731, 1995.
37. Nelson RW: Diabetes mellitus, in Ettinger SJ, Feldman EC
(eds): Textbook of Veterinary Internal Medicine, ed 4. Phil-
adelphia, WB Saunders, 1995, pp 1510–1537.
38. Turner RC, Mairead A, Ward EA: Ultralente based insulin
regimens—Clinical applications, advantages and disadvan-
tages. Acta Med Scand 671:75–86, 1983.
39. Turner RC, Holman RR: Optimizing conventional insulin
regimens to improve control, in Pickup JC (ed): Brittle Dia-
betes. Oxford, Blackwell Scientific Publications, 1985, pp
200–213.
40. Service RJ, Rizza RA, Hall LD: Prandial insulin require-
ments in insulin-dependent diabetics: Effects of size, time of
day, and sequence of meals. J Clin Endocrinol Metab
57:931–935, 1995.
41. Wallace MS, Kirk CA: The diagnosis and treatment of in-
sulin dependent and non-insulin dependent diabetes melli-
tus in the dog and the cat. Probl Vet Med 2:573–590, 1990.
42. Peterson ME: Endocrine diseases, in Sherding RG (ed): The
Cat: Diseases and Clinical Management, ed 2. New York,
Churchill Livingstone, 1994, pp 1465–1470.
43. Larkins RG: New concepts for treatment of non-insulin-de-
pendent diabetes mellitus. Trends Endocrinol Metab 8:187–
191, 1997.
44. Gerich JE: Oral hypoglycemic agents. N Engl J Med 321:
1231–1245, 1989.
45. Melander A, Bitzen PO, Faber O: Sulfonylurea antidiabetic
drugs: An update of their clinical pharmacology and rational
therapeutic use. Drugs 37:58–72, 1989.
46. Ford SL: NIDDM in the cat: Treatment with the oral hypo-
glycemic medication, glipizide. Vet Clin North Am Small Anim
Pract 25:599–615, 1995.
47. Meyerovitch J, Rotenberg P, Shechter Y: Vanadate normal-
izes hyperglycemia in two mouse models of non-insulin-de-
pendent diabetes mellitus. J Clin Invest 87:1286–1294, 1991.
48. Brichard SM, Pottier AM, Henquin JC: Long term improve-
ment of glucose homeostasis by vanadate in obese hyperinsu-
linemic fa/fa rats. Endocrinology 125:2510–2516, 1989.
Small Animal/Exotics
49. Cam MC, Pederson RA, Brownsey RW, et al: Long-term ef-
fectiveness of oral vanadyl sulphate in streptozotocin-diabet-
ic rats. Diabetologia 36:218–224, 1993.
50. Plotnick AN, Greco DS, Crans DC: Oral vanadium com-
pounds: Preliminary studies on toxicity in normal cats and
hypoglycemic potential in diabetic cats (Abstr). J Vet Intern
Med 9:181, 1995.
51. Brichard SM, Bailey CJ, Henquin JC: Marked improvement
of glucose homeostasis in diabetic ob/ob mice given oral
vanadate. Diabetes 39:326–332, 1990.
52. Yuen VG, Pederson RA, Dai S, et al: Effects of low and high
dose administration of bis(maltolato)oxovandium (IV) on fa/fa
Zucker rats. Can J Physiol Pharmacol 74:1001–1009, 1996.
53. Greco DS: Treatment of type II diabetes mellitus in cats with
oral vanadium (Abstr). Diabetes 46:1289, 1997.
54. Crenshaw KL, Peterson ME, Heeb LA: Serum fructosamine
concentration as an index of glycemia in cats with diabetes
mellitus and stress hyperglycemia. J Vet Intern Med 10:360–
364, 1996.
55. Saltiel AR, Olefsky JM: Thiazolidinediones in the treatment
of insulin resistance and type II diabetes. Diabetes 45:1661–
1669, 1996.
Compendium May 2000
56. Suter SL, Nolan JJ, Wallace P, et al: Metabolic effects of
new oral hypoglycemic agent CS–045 in NIDDM subjects.
Diabetes Care 15:193–203, 1992.
57. Kumar S, Boulton AJM, Beck-Nielsen H, et al: Troglita-
zone, an insulin action enhancer, improves metabolic con-
trol in NIDDM patients. Diabetologia 39:701–709, 1996.
58. Bailey CJ, Turner RC: Metformin. N Engl J Med 334:
574–579, 1996.
59. Kraus MS, Calvert AC, Jacobs GJ, et al: Feline diabetes melli-
tus: A retrospective mortality study of 55 cats (1982–1994).
JAAHA 33:107–111, 1997.
About the Authors
Dr. Behrend is affiliated with the Department of Small Ani-
mal Surgery and Medicine, Auburn University, Alabama.
Dr. Greco is affiliated with the Department of Clinical Sci-
ences, Colorado State University, Fort Collins, Colorado.
Drs. Behrend and Greco are Diplomates of the American
College of Veterinary Internal Medicine.