ENDOCRINOLOGY 0195-5616/01 $15.00 + .

00

MANAGEMENT OF CANINE
DIABETES
Linda M. Fleeman, BVSc, MACVSc,
and Jacqueline S. Rand, BVSc, DVSc

Diabetes mellitus is one of the most frequent endocrine diseases

affecting middle-aged and older dogs. One in 500 dogs visiting a veteri-
nary hospital was diagnosed with diabetes in a large multi-institutional
survey that was performed over 20 years ago. 61 Breed predisposition
exists, 46• 61 and familial predisposition has been reported in Samoyed
dogs 54 and Miniature Poodles38 and documented by the authors in Rott-
weiler dogs. Unfortunately, recent data on prevalence and survival of
diabetic dogs are lacking. In a review of diabetic dogs written 24 years
ago, 50% were alive 2 months after initial diagnosis and went on to be
successfully managed in the home environment, often for periods of
several years. 59 Major improvements in the level of care and therapy
available for diabetic dogs have been achieved since that time, and it
would be reasonable to assume that the survival rate is now higher.

CLASSIFICATION AND PATHOGENESIS OF CANINE

DIABETES

In human beings, the current classification divides diabetes mellitus

into type 1, type 2, other specific types of diabetes, and gestational
diabetes. 86 At present, there are no internationally accepted criteria for
the classification of diabetes in dogs. If the criteria established for human
beings are applied to dogs, most diabetic dogs would be classified as
type 1.

From The Department of Companion Animal Sciences (LMF, JSR), and Companion Animal
Centre for Diabetes and Obesity (LMF, JSR), The University of Queensland, St Lucia,
Australia

VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE

VOLUME 31 • NUMBER 5 • SEPTEMBER 2001 855

856 FLEEMAN & RAND

Type 1 diabetes is characterized by pancreatic 13-cell destruction

leading to absolute insulin deficiency. In people, this usually occurs via
cell-mediated autoimmune processes and is associated with multiple
genetic predispositions and poorly defined environmental factors. 86 In a
few cases, markers for immune destruction are lacking and the cause of
13-cell destruction is unknown. The rate of progression to absolute insulin
deficiency is quite variable. It can be rapid in young children and much
slower in patients over 30 years of age. This latter group has latent
autoimmune diabetes of adults and may retain residual 13-cell function
for many years. 97
Although the cause of 13-cell destruction in diabetic dogs is often
unknown, there is evidence that immune-mediated processes do occur.
Inflammatory cell infiltration of islets occurs in 46% of diabetic dogs, 1
and serum-associated cytotoxicity to 13 cells has been demonstrated.78
The recent finding that approximately 50% of diabetic dogs have circulat-
ing antibodies against 13 cells lends support for the existence of humoral
autoimmunity. 23 • 47 These antibodies probably target an antigen in the 13-
cell membrane to initiate destruction, although it is possible that they
are merely a consequence of 13-cell destruction.
Most diabetic dogs have absolute insulin deficiency, because circu-
lating connectingpeptide (C-peptide) values are significantly lower than
those of healthy dogs. 6• 29• 66• 84 C-peptide connects the A and B chains of
insulin within the proinsulin molecule. Cleavage of proinsulin results in
the formation of equimolar concentrations of C-peptide and insulin,
which are stored within 13-cell granules and subsequently released to-
gether during exocytosis. 53• 77 Analysis of blood levels of C-peptide is
preferred for assessing 13-cell function in diabetics rather than insulin
concentration, because administration of exogenous insulin is not mea-
sured by C-peptide assays. 73 Although most diabetic dogs have low
levels of C-peptide, some have evidence of residuall3-cell function based
on basal and glucagon-stimulated serum C-peptide concentrations. 66
This range of C-peptide concentrations in diabetic dogs is consistent with
a process of progressive destruction of 13-cells. The rate of progression to
absolute insulin deficiency has not been studied in diabetic dogs, but it
is possible that these dogs resemble human patients with latent autoim-
mune diabetes of adults. This form of type 1 diabetes occurs in middle-
aged and older patients and is characterized by gradual 13-cell destruc-
tion over months or years.
Evidence of acute or chronic pancreatitis occurs in approximately
40% of diabetic dogs. 1• 3• 19• 20 • 25• 43• 59 This association between canine
diabetes and exocrine pancreatic disease is interesting, because a similar
association does not exist in human beings. Activation of pancreatic
enzymes within the acinar tissue or duct system of the pancreas initiates
pancreatitis,83 and involvement of islet cells could then occur by exten-
sion of necrosis and inflammation into surrounding tissue. The pancreas
has a large functional reserve, however, and progressive destruction of
pancreatic tissue by recurrent or chronic pancreatitis is a rare cause of
exocrine pancreatic insufficiency and diabetes in dogs. 95 It is possible
 MANAGEMENT OF CANINE DIABETES 857

that pancreatitis may play some role in the development of immune-

mediated destruction of ~ cells in susceptible dogs or, alternatively, that
the diabetic state may be a risk factor for pancreatitis in this species.
If the criteria established for human beings are used, 86 some forms
of diabetes that occur in dogs can best be classified as "other specific
types of diabetes." An inherited early-onset form of diabetes character-
ized by aplasia of islet ~ cells in a line of Keeshond dogs57 is one
example. The rare cases of coexisting exocrine pancreatic insufficiency
and diabetes resulting from end-stage pancreatitis probably also belong
within this classification. Endocrinopathies, particularly hyperadrenocor-
ticism, which cause glucose intolerance, insulin resistance, and overt
diabetes25• 34• 66 • 72• 89• 90 would constitute most other specific types of diabe-
tes in dogs.
Gestational diabetes is defined in human beings as any degree of
glucose intolerance with onset or first recognition during pregnancy.H" If
overt diabetes persists after the pregnancy ends, it is reclassified as type
1, type 2, or other specific types of diabetes. Reduced insulin sensitivity
occurs in healthy bitches by day 30 to 35 of gestation64 and becomes
more severe during late pregnancyY The diestrus phase of the nonpreg-
nant cycle of the bitch is similar in duration to the 9 weeks of pregnancy,
and it is generally agreed that the hormone profiles during diestrus
and pregnancy are essentially identicaP 8• 27• 51 The reduction in insulin
sensitivity is more pronounced during pregnancy than during diestrus,64
however, and the alteration in the metabolic control of growth hormone
during gestation may be pregnancy-specific in dogs. 18 Nevertheless,
progesterone elevation does cause glucose intolerance and overt diabetes
during diestrus in bitches. 22·B0 Progesterone also stimulates the mammary
gland of bitches to produce growth hormone, which is a potent inducer
of insulin resistance. 82 Consequently, if diabetes is diagnosed in a bitch
during either pregnancy or diestrus, it probably should be classified as
being comparable to human gestational diabetes.
There are no well-documented studies demonstrating convincingly
that type 2 diabetes is a significant disease entity in dogs. Type 2 diabetic
people have insulin resistance and usually have relative rather than
absolute insulin deficiency. 86 Low insulin sensitivity (insulin resistance)
is genetically determined and is compounded by obesity and physical
inactivity. In the prediabetic stages of the disease, a compensatory in-
crease in insulin secretion occurs so that normoglycemia is maintained.
Eventually, the capacity to increase insulin secretion is exhausted, and
type 2 diabetes ensues. Although obesity causes insulin resistance in
dogs,63• 88 it is not recognized as a risk factor for canine diabetes.

PRESENTING CLINICAL SIGNS OF DIABETES IN

DOGS

Dogs with uncomplicated diabetes mellitus classically present with

polyuria, polydipsia, weight loss, an increased appetite, and lethargy.
858 FLEEMAN & RAND

Most affected dogs are over 7 years of age, and female dogs are at
greater risk than male dogs. 59, 61 The onset of these classic clinical signs
is typically insidious, ranging from weeks to months in duration, 59 and
may initially be unnoticed or considered insignificant by the dog's
owner. If ketosis and metabolic acidosis develop, more serious systemic
signs such as vomiting and anorexia are seen and prompt owners to
seek veterinary care more rapidly. Approximately 40% of diabetic dogs
were found to have already developed ketosis by the time they were
first presented to a university teaching hospital. 59 This progression to a
more complicated diabetic patient often coincides with the development
of concurrent disease such as pancreatitis or bacterial urinary tract
infection.
Cataract formation is the most common, and one of the most im-
portant, long-term complications associated with diabetes in dogs. 5 Cata-
racts are irreversible and can progress quite rapidly. The risk of cataract
development seems to be unrelated to the level of hyperglycemia and
increases with age. 79 About 30% of diabetic dogs already have reduced
vision at presentation. 40 Cataracts develop within 5 to 6 months of
diagnosis in most diabetic dogs and, by 16 months, approximately 80%
of such dogs have significant cataract formation. 5

AIMS OF THERAPY FOR CANINE DIABETES

The three primary aims of therapy for diabetic dogs are:

• Resolution of all clinical signs
• Avoidance of insulin-induced hypoglycemia
• Resumption of usual lifestyle and exercise level
Lethargy tends to resolve rapidly, and dogs become more active
and responsive soon after initiation of insulin therapy. Weight loss is
usually arrested before optimal glycemic control is achieved, but com-
plete resolution of the polyuria and polydipsia does not occur until the
blood glucose can be kept below the renal threshold most of the time. In
most diabetic dogs, the process of cataract formation has unfortunately
already been initiated before control of hyperglycemia is achieved.

INSULIN THERAPY

Administration of exogenous insulin is the mainstay of therapy in

all affected dogs. Even diabetic dogs with residualj3-cell function usually
have inadequate insulin secretory capacity to allow successful manage-
ment with oral hypoglycemic drugs. Animals with insulin resistance
secondary to conditions such as hyperadrenocorticism or diestrus benefit
from insulin therapy if they develop persistent hyperglycemia, even if
the hyperglycemia is relatively mild (e.g., blood glucose values of 235-
290 mg/dL [13-16 mmol/L]). Chronic hyperglycemia causes insulin
 MANAGEMENT OF CANINE DIABETES 859

resistance in peripheral tissues as well as marked suppression of insulin

secretion and destruction of ~-cells. 75 Loss of ~~cells and permanent
diabetes may occur in dogs within 2 weeks of chronic hyperglycemia
above 250 mg/ dL (14 mmol/L). 48 It is critical to introduce insulin ther-
apy early so that hyperglycemia is reduced and further ~-cell suppres-
sion and loss can be prevented. Delaying insulin therapy until more
severe hyperglycemia and clinical signs develop reduces the likelihood
of diabetic remission in dogs with gestational or diestrus- or hyperadreno-
corticism-associated diabetes. Exogenous insulin remains the most reli-
able and effective way to control hyperglycemia in dogs.

Avoid Hypoglycemia: Be Conservative with Insulin

Therapy

Severe hypoglycemia resulting from insulin overdose can cause

irreversible brain damage and death. Mild clinical signs include weak-
ness, restlessness, pacing, anorexia, and diarrhea; in severe cases, associ-
ated signs can progress to ataxia, blindness, seizures, and coma. 93 Insulin
overdose occurs less frequently in diabetic dogs than in diabetic cats
and is more likely to be avoidable in dogs by careful attention to
management practices and concurrent medical conditions. 93 Avoidance
of insulin-induced hypoglycemia is one of the primary aims of therapy
of diabetic dogs. If a conservative approach to insulin dosing is used,
the risk of this serious complication can be greatly reduced.
Hypoglycemia unawareness is a common feature of type 1 diabetes
in human beings and is associated with an increased risk of severe
hypoglycemic episodes. 8' 65 It manifests as an absence of the warning
symptoms of hypoglycemia (hunger, sweating, anxiety, palpitations, irri-
tability, and tremor), allowing acute unexpected development of the
more serious symptoms of cognitive dysfunction (confusion, dizziness,
blurred vision, weakness, loss of consciousness, seizures, and coma). It
is related to the duration of diabetes, the degree of glycemic control, and
a history of hypoglycemic episodes, 65 which may be asymptomatic. 90
Hypoglycemia unawareness and the resulting severe hypoglycemic epi-
sodes are a consequence of changes in cerebral glucose transport and in
the catecholamine-mediated counterregulatory response. Hypoglycemia.
accelerates cerebral glucose entry; thus, during subsequent hypoglyce-
mic episodes, the brain is less affected than normal and does not gener-
ate counterregulatory responses and the warning signs.8 If the blood
glucose concentration then falls even further, cerebral glucose transport
cannot be maintained and suddenly decreases. The clinical signs of
hypoglycemia are then acute and severe. Impaired counterregulatory
response to low blood glucose concentrations also exisf.37 ' 56 In type 1
diabetics, there is progressive reduction in the catecholamine-mediated
counterregulatory response to hypoglycemia. 9 This reduction in count-
erregulatory response may initially be associated with a compensa-
tory increase in peripheral tissue sensitivity to catecholamines37; how-
860 FLEEMAN & RAND

ever, this compensatory response is eventually lost, 56 and hypoglycemia

unawareness ensues. Elimination of frequent hypoglycemic episodes
can lead to recovery of peripheral sensitivity to catecholamines and
restoration of awareness. 37 Hypoglycemia unawareness is particularly a
problem when intensive insulin therapy regimens that aim for norma-
glycemia are not combined with a program for prevention of hypoglyce-
mia.8
It is unknown whether hypoglycemic unawareness could present a
similar problem for diabetic dogs if therapy aimed at normoglycemia is
pursued. An impaired glucagon counterregulatory response to insulin-
induced hypoglycemia was identified in 7 of 12 diabetic dogs. 21 Episodes
of clinical hypoglycemia had been observed in 5 of the 7 dogs with
impaired responsiveness and in none of the 5 diabetic dogs with a
normal counterregulatory response. In another report, persistent absence
of glucosuria had been recorded in some diabetic dogs before an episode
of clinical hypoglycemia. 93 Unexpected episodes of severe hypoglycemia
may occur in diabetic dogs that receive minimal blood glucose monitor-
ing for periods of many months, because such dogs display signs of
good glycemic control. Until more is known about hypoglycemia un-
awareness in diabetic dogs, it would be prudent to always err on the
side of caution and take a conservative approach to insulin therapy. This
can be best achieved by simply aiming for the minimum insulin dose
that controls an individual dog's clinical signs rather than endeavoring
to achieve normoglycemia.
The risk of insulin overdose is higher when dogs receive insulin
once daily rather than twice dailT5 and is more likely to occur when
there is good glycemic control, resulting in lower blood. glucose levels
at the time of insulin administration. There are also a variety of manage-
ment and medical factors that can result in insulin overdose. 93 These
include incomplete mixing of insulin suspensions, administration of
insulin at irregular intervals, inappetence, excessive exercise, and im-
proved insulin sensitivity associated with the end of diestrus or treat-
ment of concurrent disease such as hyperadrenocorticism. Care must be
taken when dispensing insulin syringes to owners to ensure that there
is no confusion regarding dosing. For example, the graduations on many
1-mL insulin syringes are equal to 2 U, although graduations on most
0.5-mL insulin syringes are equal to 1 U. Graduations on syringes
designed for use with 100 U/mL of insulin represent a different volume
from graduations on syringes designed for use with 40 U/mL of insulin,
and this may also lead to dosing errors.

Choosing the Right Insulin Preparation

A variety of insulin preparations are commonly available. Regular

and semilente insulins are characterized by rapid action and short dura-
tion of effect and are generally useful only for the initial intensive
management of dogs with diabetic ketoacidosis. Longer-acting prepara-
 MANAGEMENT OF CANINE DIABETES 861

tions such as ultralente, protamine zinc (PZI), and isophane (NPH) are
more suited for outpatient management because they provide continued
insulin supplementation for many hours after a single injection. Pre-
mixed combinations of short-acting and longer-acting insulins are valu-
able for the treatment of diabetic dogs. One common example is lente
insulin, which contains a mixture of semilente and ultralente and results
in a relatively predictable and rapidly obtained peak effect. 13 A number
of combinations of regular and NPH insulin are also widely available.
Good glycemic control can be achieved with most insulin preparations,
but some are easier to use because they have a more predictable effect
in different dogs and in the same dog. Generally, the longer the duration
of action of insulin, the greater is the variability in response between
dogs receiving the same dose.
When choosing the type of insulin for long-term use in a diabetic
dog, another consideration is the species of the exogenous insulin. Por-
dne insulin has exactly the same amino acid sequence as canine insulin
and induces no anti-insulin antibodies with prolonged use in dogs. 14• 28•
"'- 71 Human insulin differs by one amino acid from canine insulin, and
anti-insulin antibodies have only been detected in one dog treated with
recombinant human insulin. 44 Bovine insulin differs by two amino acids
from canine insulin. Anti-insulin antibodies have been detected in dogs
treated with purified bovine insulin71 and mixed bovine/porcine insu-
lin.28· 44 Anti-insulin antibodies may make it difficult to achieve glycemic
control in some diabetic dogs treated with bovine/porcine insulin. 44 It is
recommended to change to porcine or human insulin if difficulties with
control are evident when using bovine insulin. Alternatively, it may be
advisable to avoid preparations that contain bovine insulin.
Human recombinant insulins are usually sold at a concentration of
100 U/mL. In some countries, porcine lente insulin or bovine/porcine
PZI insulin is available as a veterinary product at a concentration of 40
U/mL. These more dilute preparations are useful for smaller dogs,
which may require a total insulin dose of only 1 or 2 U. Syringes that
measure insulin unit increments are available for both insulin concentra-
tions. Insulin dosing pens are obtainable for NPH insulin and the pre-
mixed combinations of regular and NPH insulin and are convenient for
use in diabetic dogs. 87 Most of these dosing pens allow injection of a
minimum dose of 2 U and increase in 1-U increments, making them a
practical tool for smaller patients.
In summary, either lente, NPH, or premixed combinations of regular
and NPH insulin administered twice daily is the therapy favored for
long-term management of diabetic dogs by most clinicians. Porcine or
human insulin is considered more reliable than preparations containing
bovine insulin, although clinical problems with antibodies to bovine
insulin are rarely reported. Longer-acting insulins such as ultralente and
PZI tend to be less predictable because the peak action is more variable.
Choose one or two insulins for the practice, and use these on all diabetic
patients so that knowledge of their action is gained. Generally, 40 U I
mL insulin is good for small to medium-sized dogs, although 100 U I
862 FLEEMAN & RAND

mL insulin is more cost-effective for large dogs. Great care must be

taken to avoid dosing errors with different types of syringes, especially
if both insulin concentrations are used in the practice.

Frequency of Insulin Administration: Once or Twice a

Day?

A recent study showed that 94% of diabetic dogs were successfully

managed with twice-daily insulin dosing. 45 High doses of insulin and
episodes of hypoglycemia were more common in the diabetic dogs that
received insulin only once daily. 45 Most diabetic dogs initially seem to
have intact counterregulatory mechanisms to low blood glucose levels
and are able to compensate for the increased glucose-lowering effect of
a high-dose once-daily dosing regimen. We frequently see dogs on more
than double the dose of insulin required to maintain glycemic control
that have no clinical evidence of hypoglycemia. These dogs may be at
risk for developing severe hypoglycemia if there is deterioration of their
counterregulatory mechanisms. The diabetic dogs that we have observed
with unexpected episodes of severe hypoglycemia after many months
of good glycemic control have often been receiving once-daily insulin
injections. We believe that adopting a twice-daily insulin-dosing regimen
at the outset for all diabetic dogs is a safer option.
Although treatment regimens comprising once-daily insulin injec-
tions are considered by some to be simpler and more convenient, most
of these regimens involve feeding two meals each day, one soon after
the insulin injection and another at the time of peak insulin activity
about 8 hours later. Given the length of the usual working day, it may'
actually be more convenient for people to feed the second meal 12 hours
after the first. Experienced owners rarely report any difficulty with the
administration of insulin injections, and if they are required to be at
home to feed the dog, it is little more effort to give the dog an insulin
injection at the same time. As a result, many clinicians favor treatment
regimens that involve administration of the same dose of insulin along
with feeding of identically sized meals every 12 hours.

Choosing the Initial Insulin Dose: Where to Start?

Therapy using insulin with a rapid action and short duration of

effect such as regular or semilente insulin is useful for the initial inten-
sive management of dogs with diabetic ketoacidosis. A variety of proto-
cols are used, ranging from continuous intravenous infusion of insulin
to intramuscular injections every 1 to 2 hours or every 4 to 6 hours. 15• 26
Treatment with longer-acting preparations can be started once the dog's
condition has been stabilized and inappetence has resolved. Dogs that
are eating well at the time of diagnosis can begin therapy with longer-
acting insulin immediately.
 MANAGEMENT OF CANINE DIABETES 863

Blood glucose should be measured before the first dose of longer-

acting insulin is administered. Our recommendation is that an initial
insulin dose of 0.5 U /kg should be administered if the blood glucose
value is 360 mg/ dL (20 mmol/L) or more. If the blood glucose value is
less than this, a lower starting dose of 0.25 U /kg should be used. Several
blood glucose measurements should then be taken during the period of
expected maximal insulin action (usually 2-8 hours after administration)
to assess the risk of hypoglycemia before the dog is discharged from the
hospital. If the blood glucose value remains above 150 mg/ dL (8 mmol/
L) after the first injection and is above 270 mg/dL (15 mmol/L) when
the next two insulin injections are due, it is likely to be safe to send the
dog home on this dose of insulin. Attention should be given to the
glucose-lowering effect of the insulin dose. If the baseline blood glucose
value is highly elevated and the effect of the first dose of insulin is to
drop the blood glucose value considerably, it is possible that hypoglyce-
mia may be a risk after several consecutive doses have been adminis-
tered. An example would be a dog with a baseline blood glucose value
higher than 550 mg/ dL (30 mmol/L), which then falls almost to our
cutoff point of 150 mg/ dL (8 mmol/L). If the same dose of insulin were
to be administered when this dog had a lower baseline blood glucose
value, there would be a risk of hypoglycemia. It is also important to
ensure that too high an insulin dose is not used from the outset, because
insulin sensitivity improves once chronic hyperglycemia resolves, re-
sulting in an even greater risk of hypoglycemia after several weeks of
therapy. If the initial response to insulin seems inadequate, it is not
necessary to immediately increase the dose. Instead, it is preferable to
allow the dog to equilibrate on the initial dose 'for at least a few days.
Clinical improvement, with a reduction in lethargy, polydipsia, and
weight loss, is typically apparent before there is good glycemic control.
Remember that it is always safest to err on the side of caution when
deciding on the dose of insulin on which to send a diabetic dog home.
If there is any doubt, it is preferable to lower the dose and monitor the
dog in the hospital for another day rather than risk the life-threatening
possibility of hypoglycemia.

ORAL HYPOGLYCEMIC AGENTS

A number of oral hypoglycemic agents are available, primarily for

the treatment of type 2 diabetes in people. The sulfonylurea drugs,
which include glipizide, glyburide, glibenclamide, and tolbutamide, act
to amplify insulin secretion from l3-cells?4 Diabetic dogs do not have
sufficient 13-cell function to allow these drugs to be an effective form
of therapy.
Oral hypoglycemic agents that influence aspects of glucose homeo-
stasis other than 13-cell function are potentially useful as adjunctive
treatments in diabetic dogs receiving insulin therapy. Acarbose competi-
tively inhibits a-amylase and a-glucosidase in the intestine and thus
864 FLEEMAN & RAND

delays absorption of glucose and blunts postprandial hyperglycemia. 76

Side effects include weight loss, flatulence, and soft to watery feces.
Acarbose is effective in improving glycemic control in insulin-treated
diabetic dogs. 69 Because of the cost and incidence of adverse effects,
however, acarbose therapy should be reserved for treatment of poorly
controlled diabetic dogs in which the cause of inadequate glycemic
control cannot be identified and insulin treatment alone is ineffective in
preventing clinical signs of diabetes.
Chromium picolinate is a dietary mineral supplement that increases
the clearance rate of glucose from the blood by approximately 10% in
healthy dogs. 85 It is thought to potentiate insulin's ability to store glucose
and would theoretically be a useful adjunct to exogenous insulin therapy.
Treatment with chromium picolinate has not been found to improve
glycemic control in insulin-treated dogs, however. 81
Oral drugs that improve insulin action, that is, increase insulin
sensitivity, are widely used in human patients with type 2 but not type
1 diabetes. These drugs include biguanides such as metformin and
thiazolidinediones such as troglitazone, pioglitazone, and rosigilitazone.
Although there are short-term studies in normal dogs and dogs with
experimentally induced diabetes,62 there is no information available on
the long-term effects of these drugs in diabetic dogs. Their use would
be confined to the few diabetic dogs that are poorly controlled and have
evidence of insulin resistance that cannot be corrected. In most diabetic
dogs, increasing the insulin dose is sufficient to overcome insulin resis-
tance and achieve glycemic controL .
In summary, oral hypoglycemic agents have limited use as an ad-
junct to insulin therapy in diabetic dogs. Acarbose is the only drug that
has been shown to be clinically effective. Good glycemic control is
readily achieved in most diabetic dogs with insulin therapy alone. If
treatment with insulin fails to adequately control clinical signs, careful
evaluation for an underlying cause of poor control should be performed.
If the reason cannot be identified and corrected, therapy with acarbose
may reduce hyperglycemia.

DIETARY RECOMMENDATIONS FOR DIABETIC DOGS

Ideally, diabetic dogs should eat just before the expected time of
peak insulin activity. Dogs should be fed within 4 hours of administra-
tion of lente insulin14 or 1 to 8 hours after NPH insulin. In our experience,
a feasible compromise is to feed the dog immediately after the insulin
injection. This considerably simplifies the home treatment regimen for
most dog owners and still allows good glycemic control to be readily
achieved. In addition, many owners prefer this regimen because they
believe that their pet is rewarded for submitting to the injection.
The most important principle of feeding diabetic dogs is to provide
sufficient calories to achieve and maintain optimal body condition. Dogs
with poorly controlled diabetes have a decreased ability to metabolize
 MANAGEMENT OF CANINE DIABETES 865

the nutrients absorbed from their gastrointestinal tract and lose glucose
in their urine; thus, they require more calories for maintenance than
healthy dogs. Good glycemic control is readily achieved in most diabetic
dogs when they are fed a nutritionally balanced maintenance diet. It is
crucial that the diet fed should be palatable so that food intake is
predictable. Because the daily insulin-dosing regimen tends to be fixed
for diabetic dogs, it is important that a predictable glycemic response is
achieved after each meal. Consequently, every meal should contain
roughly the same ingredients and calorie content and should be fed at
the same time each day. The owners of diabetic dogs should be aware
that a consistent insulin-dosing and feeding routine is optimal, although,
for practical reasons, a certain amount of compromise may be necessary
and, in most dogs, is well tolerated. The dietary recommendations for
diabetic dogs are summarized in Table 1.
Obesity causes insulin resistance in dogs 63, 88 and has a detrimental
effect on glycemic control in animals with diabetes. Some dogs are still
obese when diabetes is diagnosed even though they have experienced
weight loss. Insulin therapy ends this state of catabolism, and weight
loss should soon be arrested. It is then important to begin a feeding
regimen that allows the dog to gradually reduce to an optimal body
weight. Insulin is an anabolic hormone, and dogs on high doses seem
prone to obesity.

Table 1. SUMMARY OF CURRENT DIETARY RECOMMENDATIONS FOR DIABETIC

DOGS

Dietary Factor Current Recommendation

Calorie intake Achieve and maintain optimal body condition
Primary nutritional Palatable
requirements Nutritionally balanced
Consistency is important; the same food containing a
standard number of calories should be fed after
each insulin injection
Other nutritional Increased complex carbohydrate content with a high
recommendations proportion of insoluble fiber incorporated into the
food
Decreased fat content, particularly if there is
concurrent pancreatitis
Timing of meals Postprandial period should ideally coincide with the
period of maximal exogenous insulin activity
If a diabetic dog is receiving insulin injections twice
daily, a practical option is to feed two equal-sized
meals per day, each immediately after the injection
Diabetic dogs with concurrent The nutritional requirements of any concurrent
disease disease should take precedence over the dietary
therapy for diabetes
Regardless of the diet fed, glycemic control can still
be maintained with exogenous insulin therapy

*From Fleeman LM, Rand JS: Long-term management of the diabetic dog. Waltham Focus 10:16,
2000; with permission.
866 FLEEMAN & RAND

The nutritional requirements of any concurrent disease should take

precedence over the dietary therapy for diabetes. Regardless of the diet
fed, glycemic control can still usually be maintained with exogenous
insulin therapy. Evidence of acute or chronic pancreatitis has been re-
ported to occur in about 40% of diabetic dogs. 3• 19• zo, 25 • 43• 59 High-fat diets
and hypertriglyceridemia have been proposed as possible inciting causes
of canine pancreatitis,94 and low-fat diets are recommended for dogs
with chronic pancreatitis. Episodes of acute pancreatitis are a serious
complication in diabetic dogs/ 9• 59 because glycemic control can be lost
and higher doses of insulin may be temporarily required. Conversely,
hypoglycemia may occur when dogs with pancreatitis that are anorectic
and vomiting receive their usual dose of insulin.
It is now highly recommended that 55% to 60% of a diabetic per-
son's total energy be provided from carbohydrates and that most carbo-
hydrates should be complex, containing high amounts of resistant starch
and soluble fiber. 2• 52 Dietary effects can be quite subtle in people with
type 1 diabetes and result in no lowering of insulin dose. 58 Although
there is no doubt that a considerable amount of the information known
about dietary recommendations for human patients is also relevant to
dogs, it is clear that the specific requirements of diabetic dogs still need
further clarification. Studies in diabetic dogs indicate that high-fiber
diets may also be associated with improved glycemic controF 42• 55• 68• 70;
however, in contrast to the findings in human beings, there seems to be
a tendency for improved glycemic control and fewer side effects with
diets containing increased insoluble fiber rather than soluble fiber. 55• 67• 70
High-fiber diets, if palatable, can be tried to see if glycemic control
improves.
Importantly, there seems to be marked variation between the re-
sponses of individual diabetic dogs to dietary fiber. In one study,68
significant improvement of all indices of glycemic control, including a
lowered daily insulin requirement, was seen in 9 of 11 dogs when they
were fed a high-fiber diet. The remaining 2 dogs were found to have
improved glycemic control on the low-fiber diet. In another study that
investigated more subtle differences between the fiber content of diets,
individual variability was also evident. 67 Six diabetic dogs had the best
glycemic control on a diet containing moderate amounts of mixed insolu-
ble and soluble fiber, although 4 dogs had the best glycemic control on
a high insoluble fiber diet and 1 dog did best on a moderate insoluble
fiber diet. This individual variability in response may be partly a result
of the side effects that are sometimes associated with high-fiber diets,
which include poor palatability, poor weight gain, poor hair coat, volu-
minous feces, flatulence, diarrhea, and constipation.
Information regarding the long-term influence on glycemic control
in diabetic dogs is available for only a small number of commercially
available diets. 55 More information is needed on how commercial high-
fiber diets influence the clinical management of canine patients com-
pared with typical maintenance moderate-fiber diets, which are usually
being consumed at the time of initial diagnosis of diabetes. In our
 MANAGEMENT OF CANINE DIABETES 867

experience, excellent clinical control of diabetes can be achieved using

commercial diets designed for maintenance of healthy adult dogs. Own-
ers of diabetic dogs often prefer maintenance diets and more often
complain about palatability and side effects with high-fiber diets. Be-
cause one of the main effects of a high-fiber diet is to slow intestinal
glucose absorption, the fiber should always be incorporated in the food
rather than given separately as a supplement.

ESTABLISHING A PRACTICAL ROUTINE FOR THE

OWNER

One of the primary aims of therapy is to avoid insulin-induced

hypoglycemia. Every person in the diabetic dog's household needs to
be aware of this life-threatening complication, which can rapidly develop
into a frighte)1ing emergency. The importance of avoiding an insulin
overdose cannot be overemphasized. If some insulin is spilt during
injection, the owner should never give more at that time, even if it seems
that the dog has received no insulin. If the owner is ever uncertain, the
safest option is to withhold the injection, because the consequences of
missing a single insulin dose are negligible. The clinical signs seen in
dogs with hypoglycemia are listed in Figure 1. If mild signs of hypogly-
cemia develop, the owner should feed a meal of the dog's usual food. If

Lethargy

Altered mentation

Dog often appears dull and unaware of surroundings

Owners may fmd it difficult to attract the dog's attention

Trembling is often noticed.

Weakness and ataxia

Collapse and loss of consciousness

Epileptiform seizures

Figure 1. Progression of clinical signs as hypoglycemia becomes more severe in dogs.

(From Fleeman LM, Rand JS: Long-term management of the diabetic dog. Waltham Focus
10:16, 2000; with permission.)
868 FLEEMAN & RAND

the dog is unwilling or unable to eat, syrup containing a high glucose

concentration can be administered orally. Suitable syrups are marketed
for use by human diabetics and should be kept in reserve by all owners
of diabetic dogs. When the dog recovers, food should be fed immedi-
ately. The owner should contact his or her veterinarian as soon as
possible, at which point, a SO% reduction in insulin dose is usually
recommended. If the dog is due for an insulin injection before the
veterinarian can be contacted, this injection should be withheld.
The aim of long-term therapy of diabetic dogs is simply to achieve
resolution of clinical signs. In other words, well-controlled diabetic dogs
are active and alert, maintain optimal body condition, are not polyuric
or polydipsic, and have no ketonuria. It is usually possible to introduce
a number of modifications to the treatment strategy of individual dogs
to reduce the disruption to the owner's lifestyle without compromising
the clinical response of the dog. Care should be taken to consider each
case individually. Most owners of diabetic dogs take 1 to 2 weeks
to establish a daily treatment routine and to become accustomed to
administration of subcutaneous injections.

HOME MONITORING OF GLYCEMIC CONTROL

Although many owners of diabetic dogs welcome the opportunity

to monitor glycemic response at home, compliance can be variable. The
primary aim of therapy is to achieve resolution of clinical signs; thus, it
is important to regularly monitor signs such as water intake and body
weight. We recommend that all diabetic dog owners make a daily record
of their pet's appetite and general demeanor, particularly noting any
lethargy. On 1 day each week, we also recommend that they measure
the dog's body weight and 24-hour water intake and obtain a dipstick
reading for glucose and ketones from a random urine sample. If they
have any difficulty with the weekly measurements, we usually suggest
that the dog be brought to the hospital to obtain the required informa-
tion.
Review of the owner's home log and physical examination of the
dog should be performed regularly by the veterinarian in charge of the
case. This should be done approximately every 2 weeks during the
initial stabilization period. Once the veterinarian has established a "feel"
for the case and a close rapport with the owner, the frequency of
assessment may be gradually reduced. The aim for all diabetic dogs is
complete resolution of the clinical signs of lethargy, weight loss, polydip-
sia, and ketonuria. It is preferable that some glucosuria is always present,
because persistent negative urine glucose measurements may indicate
subclinical hypoglycemia.
If water intake is greater than 60 mL/kg/ d or the dog is lethargic
or losing weight, adjustment of the dog's insulin dose is probably
required.U If persistent negative glucosuria is recorded, it is also prudent
to re-evaluate the insulin dose. Measurement of fructosamine or glyco-
 MANAGEMENT OF CANINE DIABETES 869

sylated hemoglobin is an additional way of assessing glycemic control

in diabetic dogs/ 0• 11 • 24• 39• 49• 50• 60 although monitoring clinical signs is
usually sufficient. 11 To determine how to make an appropriate adjust-
ment to a diabetic dog's insulin dose, it is necessary to evaluate serial
blood glucose measurements after the dog's usual insulin injection and
food.

SERIAL BLOOD GLUCOSE CURVE

Once it has been decided that the insulin dose of a diabetic dog
requires re-evaluation, arrangements should be made for obtaining a
serial blood glucose curve. Our standard protocol for generating a serial
blood glucose curve is to admit the dog to the hospital before administra-
tion of the morning insulin injection and obtain a baseline blood glucose
reading. The usual insulin dose and meal are then given. If the owner
does this, it provides an opportunity to review injection technique and
correct any problems. If the dog refuses to eat, subsequent blood glucose
values are likely to be lower than if the dog eats normally. In this
situation, it is probably best to cancel the serial blood glucose curve on
that day and reschedule it. The protocol can be modified on the next
occasion to allow the owner to take the dog home or to a less stressful
environment after the baseline blood glucose reading is obtained so that
the usual meal can be fed there. The dog can then be returned to the
hospital before the next blood glucose reading is due. Alternatively, the
morning preinsulin blood glucose reading can be omitted from the serial
blood glucose curve, and the dog can be brought to the hospital after
the morning insulin injection and meal have been given at home.
Blood glucose measurements are then obtained every 2 hours, ide-
ally until the next insulin injection is due. Once the dog is somewhat
controlled, a shortened curve may be obtained during the stabilization
period to decrease cost. Blood glucose should always be measured until
there is a clear increase in blood glucose levels to greater than 270 mg/
dL (15 mmol/L) after a nadir. A full 12-hour curve is recommended
when a previously well-controlled diabetic dog develops signs of poor
control or hypoglycemia. The important values are the nadir, or lowest
blood glucose reading obtained, and the preinsulin blood glucose. Blood
samples can be collected either through an indwelling catheter in a
peripheral or jugular vein31• 32 or by direct venipuncture using a fine-
gauge needle, and glucose can be measured using a portable blood
glucose meter. 16• 92
Evaluation of a serial blood glucose curve performed in a hospital
environment allows the clinician to gain some understanding of the
daily blood glucose fluctuations typical for that diabetic dog. Care must
be taken to ensure that the dog experiences minimal stress while in the
hospital and that the normal feeding and exercise routine is followed as
closely as possible.
870 FLEEMAN & RAND

EVALUATION OF SERIAL BLOOD GLUCOSE CURVES

There is an enormous amount of day-to-day variability between

blood glucose curves performed on individual diabetic dogs receiving
an identical insulin dose and meal.29• Potential reasons for this include
unavoidable variation in the dose of insulin administered, differences in
the rate of absorption from the site of subcutaneous injection, inherent
error in the meter used for measurement of blood glucose, and the
influences of a variety of counterregulatory mechanisms. Consequently,
the serial blood glucose curve is actually quite an unreliable test for
assessing the glycemic response to a given dose of insulin. Results of a
serial blood glucose curve should always be considered in conjunction
with assessment of patient history, physical examination findings, and
changes in body weight before dose changes are made.U
Our guidelines for evaluation of serial blood glucose curves in
diabetic dogs are primarily based on the nadir, or lowest blood glucose
reading obtained, and the two preinsulin blood glucose values. The first
preinsulin blood glucose value is the reading obtained before the morn-
ing insulin injection, and the second is the last blood glucose reading
taken when the next insulin injection is due, usually 12 hours later. The
nadir gives an indication of the maximal blood glucose response to the
current dose of insulin and can occur at any point in the blood glucose
curve, including just before insulin injections. The time to nadir influ-
ences recommendations for dose but can vary considerably even in the
same dog over consecutive visits. The preinsulin blood glucose values
provide an indication of the likely blood glucose level when the dog is
due for an insulin injection. This is important, because hypoglycemia is
more likely if the effects of the previous insulin injection overlap with
the next insulin dose, producing an additive effect. NPH insulin tends
to have a shorter duration and less additive effect than lente insulin.
Our guidelines are summarized as follows:
• If the nadir is less than 55 mg/ dL (3 mmol/L) or the dog shows
clinical signs of hypoglycemia, the insulin dose should be de-
creased by 50%.
• If the nadir falls within the range of 55 to 90 mg/ dL (3-5 mmol/
L) or if either of the preinsulin blood glucose values is less than
180 mg/ dL (10 mmol/L), the insulin dose should be decreased by
20% (rounded down to nearest unit of insulin). Examples are
shown in Figure 2.
• If the final preinsulin blood glucose value is less than 90 mg/ dL
(5 mmol/L), the evening insulin injection should be withheld and
the dog should be fed as usual. The insulin dose should be
decreased by 20% (rounded down to nearest unit of insulin), but
the new dosing regimen should not be commenced until the next
morning. If the final preinsulin blood glucose reading is less than
55 mg/ dL (3 mmol/L),the dose should be decreased by 50%.
 MANAGEMENT OF CANINE DIABETES 871

14 250
12
200
10
Blood
glucose 8 150 Blood
glucose
(mmoi/L) 6 100 (mgldL)
4
50
2
0 0
A 8:00AM 12:00 PM 4:00PM 8:00PM

i
20
Time
i 350
300
15 250
200
Blood 10 Blood
glucose 150 glucose
(mmoi/L) (mgldL)
5 100
50
0 0
B 8:00/Wo 12:00PM 4:00PM 8:00PM

i Time
i
Figure 2. Examples of serial blood glucose curves that indicate that the diabetic dog's
insulin dose should be decreased. If the nadir falls within the range 55-90 mg/dl (3-5
mmoVL), or if either of the preinsulin blood glucose values is less than 180 mg/dl (1 0
mmoi/L), the insulin dose should be decreased by 20% (rounded" down to nearest unit of
insulin). A, The blood glucose nadir is less than 90 mg/dl (5 mmoi/L). B, The blood glucose
stays below 180 mg/dl (1 0 mmoi/L) when the evening injection is due. Insulin and food
were administered at 8:00 AM and 8:00 PM. Samples for blood glucose measurement were
collected every 2 hours. Dotted lines indicate the upper and lower limits of the target nadir.

• If the nadir falls within the range of 90 to 145 mg/dL (5-8 mmol/
L) and both of the preinsulin blood glucose values are greater
than 180 mg/ dL (10 mmol/L), the dog is likely to have optimal
clinical control and does not require an insulin dosage adjustment.
Examples are shown in Figure 3.
• If the nadir is greater than 145 mg/ dL (8 mmol/L) and the
preinsulin blood glucose values are greater than 180 mg/ dL (10
mmol/L), the dog's insulin dose should be increased by 20%
(rounded down to nearest unit of insulin). An example is shown
in Figure 4.
• If the diabetic dog is not lethargic, has a stable body weight, has
no ketonuria, and is drinking less than 60 mL/kg/ d and an
increase or decrease in insulin dosage is suggested by the serial
blood glucose curve, insulin dosage adjustments of only 1 U are
advised regardless of the dose the dog is receiving.
872 FLEEMAN & RAND

25 450
400
20 350
Blood 300 Blood
glucose 15 glucose
250
(mmol!L) (mg!dL)
200
10
150
100
50
0 0
A 8:00AM 12:00 PM 4:00PM 8:00PM

25
i Time
i 450
400
20 350
300
Blood 15 Blood
glucose 250 glucose
(mmol/L) 200 (mg!dL)
10
150
5 100
50
0 0
B 8:00AM 12:00 PM 4:00PM 8:00PM

i Time

i
Figure 3. Examples of serial blood glucose curves that indicate that the diabetic dog's
insulin dose does not require adjustment. If the nadir falls within the range 90-145 mg/dl
(5-8 mmoi/L) and both of the preinsulin blood glucose values are greater than 180 r:ng/dl
(10 mmoi/L), the dog is likely to have optimal glycemic control and doesn't require an
insulin dosage adjustment. The nadir can occur at any point in the blood glucose curve. A,
The nadir occurs at 2:00 PM in this serial blood glucose curve. 8, The nadir occurs at 6:00
PM in this serial blood glucose curve. Insulin and food were administered at 8:00 AM and
8:00 PM. Samples for blood glucose measurement were collected every 2 hours. Dotted
lines indicate the upper and lower limits of the target nadir.

• If high blood glucose measurements are recorded in a diabetic

dog, for example, values in excess of 550 mg/ dL (30 mmol/L),
the possibility of insulin resistance or increased hepatic gluconeo-
genesis should be considered. Insulin resistance is indicated by
extremely high blood glucose readings with little glucose lowering
effect after insulin administration and can be caused by concurrent
disease or medications. On the other hand, a high initial blood
glucose reading with a good response to insulin injection (Fig.
SA) suggests increased glucose production after a hypoglycemic
episode, transient stress, or increased muscle activity such as oc-
curs with struggling. A review of the dog's history and careful
clinical assessment are necessary to determine the likely cause in
each case (Fig. 5B). Severe episodes of hypoglycemia after insulin
 MANAGEMENT OF CANINE DIABETES 873

30 500
450
25 400
20 350
Blood 300 Blood
glucose 15 250 glucose
(mmoi/L) 200 (mgldL)
10 150
5 100
50
0 0
8:00AM 12:00 Pllii 4:00PM 8:00PM

i Time
i
Figure 4. Example of a serial blood glucose cuNe that indicates that the diabetic dog's
insulin dose should be increased. If the nadir is greater than 145 mg/dl (8 mmoi/L), and
the preinsulin blood glucose values are greater than 180 mg/dl (10 mmoi/L), the dog's
insulin dose should be increased by 20% (rounded down to nearest unit of insulin). Insulin
and food were administered at 8:00 AM and 8:00 PM. Samples for blood glucose measure-
ment were collected every 2 hours. Dotted lines indicate the upper and lower limits of the
target nadir.

overdose can result in compensatory hyperglycemia. This hyper-

glycemia sometimes seems to persist for several days, and serial
blood glucose assessment performed shortly after an episode of
clinical hypoglycemia may result in a curve similar to that ob-
tained after insulin underdosing. If there is ever any doubt about
the interpretation of a serial blood glucose curve, it is always safest
to err on the side of caution and decrease the dog's insulin dose.
• The findings of the serial blood glucose curve should always be
related to the assessment of the dog's history, physical examina-
tion findings, and changes in body weight before a final decision
is made regarding insulin dose.
Good glycemic control is usually attained after at least 2 months of
regular veterinary monitoring and insulin dosage adjustment, although
a stable insulin dosage often takes 4 months or more to achieve. When
chronic hyperglycemia is well controlled, some improvement in periph-
eral insulin sensitivity occurs and the insulin dosage may need to be
decreased. This happens in most dogs soon after resolution of polydip-
sia. Once the classic signs of diabetes have resolved, further clinical
improvement occurs over several months until an optimal health and
fitness level is achieved. Shedding of the hair coat and growth of a new
coat, which may have the same color as when the dog was younger and
healthier, often mark this final stage. The last goal of long-term therapy
of diabetic dogs is resumption of the pet's usual lifestyle and exercise
level. Many diabetic dogs are elderly and are accustomed to moderate
daily exercise. Younger dogs may resume a high activity level and
874 FLEEMAN & RAND

40 700
35 600
30 500
Blood 25
400 Blood
glucose
20 glucose
(mmol/L)
300 (mgldL)
15
10 200

5 100
0 0
8:00AM 12:00 PM 4:00PM 8:00PM

A
i Time

i
B
Number of Weeks
before Blood
Glucose Curve
presented in
Figure SA Water Intake Urine Ketones Urine Glucose
3 9 mL/kg/d Negative ++
2 64 mL/kg/d Negative Negative
1 112 mL/kg/d Trace Trace

++ = Positive glucose measurement on dipstick.

Figure 5. Example of a serial blood glucose curve that indicates that insulin overdose may
be a problem. A, Assessment of the glucose lowering effect of the injected insulin reveals.
that the blood glucose was lowered from 640 mg/dl (35 mmoi/L) to 180 mg/dl (10 mmol/
L), representing a large drop of 460 mg/dl (25 mmoi/L). Insulin and food were administered
at 8:00 AM and 8:00 PM. Samples for blood glucose measurement were collected every 2 1
hours. Dotted lines indicate the upper and lower limits of the target nadir. B, Review of the
recent weekly home records of 24-hour water intake and urine glucose and ketones reveal
that some urine samples have been negative for glucose and there has been recent
recurrence of polydipsia. Historical and physical examination findings identified no evidence
of concurrent disease or medications. In this dog, the marked hyperglycemia apparent at
the start of the serial blood glucose curve may be due to counterregulation following a
recent episode of severe hypoglycemia and it is likely that this dog is receiving an insulin
overdose. It would be prudent to recommend decreasing the insulin dose by 20% (rounded
down to nearest unit of insulin) and to see if water intake decreases. This 23-kg dog was
eventually stabilized on an insulin dose 3 units lower than given here.

require further adjustment to their daily calorie intake and insulin dose
as a result.

MONITORING BLOOD GLUCOSE AT HOME

Evaluation of a serial blood glucose curve performed in a hospital

environment has long been the only recognized method for determining
how to make insulin dosage adjustments in diabetic dogs. This test is
responsible for a significant proportion of the cost of stabilizing a dia-
 MANAGEMENT OF CANINE DIABETES 875

betic dog and has inherent problems. Many diabetic dogs become anx-
ious when separated from their owners and admitted into the hospital
environment. This anxiety may be associated with inappetence or stress-
induced elevation of their blood glucose values. Recent development of
techniques for sampling capillary blood glucose from the pinna91 and
buccal mucosa 30 may allow owners of diabetic dogs to obtain data at
home regarding their pet's level of glycemic control.U This is likely to
provide an economic alternative to the hospital-based serial blood glu-
cose curve and offers a means of avoiding the problems of inappetence
and stress-induced hyperglycemia.

CONCURRENT DISEASE

Most diabetic dogs are middle-aged and older and thus are prone
to diseases that commonly affect this age group. Consequently, many
suffer concurrent problems that may cause insulin resistance and need
to be managed in combination with the diabetes. Treated diabetic dogs
have a chance of survival similar to that of nondiabetic dogs of the same
age and gender, although the hazard of death occurring is greatest
during the first 6 months of therapy. 41 When concurrent disease is
suspected, a thorough clinical evaluation by the veterinarian in charge
of the case should be performed at the earliest opportunity. If concurrent
illness causes inappetence, it is generally advisable to administer half of
the usual insulin dose so as to reduce the risk of hypoglycemia. Diabetic
dogs with a reduced appetite often eat if they are . hand-fed highly
palatable food by their owner.
Insulin resistance associated with hyperadrenocorticism occurs in
some diabetic dogs and may make glycemic control more difficult to
achieve. Hyperadrenocorticism can present a diagnostic challenge, be-
cause dogs with poorly controlled diabetes without hyperadrenocorti-
cism often have less suppression of cortisol levels after the low-dose
dexamethasone suppression test than normal dogs and dogs with well-
controlled diabetes. Chronic pancreatitis also complicates the manage-
ment of a large proportion of dogs with diabetes. Even after there is
good glycemic control, many diabetic dogs are at increased risk for
developing bacterial infections, particularly of the urinary tract and
possibly also of the skin, external ear canals, and oral cavity. Bacterial
cystitis is usually not associated with obvious clinical signs in diabetic
dogs, and results of routine urinalysis may be normaP5 Insulin-treated
diabetic dogs with a chronic urinary tract infection often have good
glycemic control; in our experience, frequently, the only clinical sign is
difficulty in maintaining body weight. A urine culture is advisable at
the time of initial diagnosis and at any time when clinical assessment
indicates that the dog's progress is not optimal. If a bitch is in diestrus
at the time of diagnosis of diabetes, insulin therapy should be initiated
immediately, and ovariohysterectomy should then be performed as soon
as there is a measurable reduction in polydipsia, indicating improvement
876 FLEEMAN & RAND

in glycemic control. Remission of diabetes is possible if the insulin

resistance associated with diestrus is treated aggressively.
Blindness and lens-induced uveitis resulting from cataract formation
develop sooner or later in most diabetic dogs and are the most important
sequelae of canine diabetes. Mild or subclinical uveitis as evidenced by
reduced intraocular pressure is present in most dogs with diabetic cata-
racts and can often be satisfactorily treated with nonsteroidal anti-
inflammatory drugs. 4 Long-term therapy with topical flurbiprofen or low
doses of oral nonsteroidal anti-inflammatory drugs are often sufficient to
manage mild lens-induced uveitis and prevent the more advanced signs
of scleral hyperemia, photophobia, and ocular discharge. Permanent
ocular damage can result if lens-induced uveitis is not treated. Surgical
removal of diabetic cataracts usually results in restoration of good vision
and marked improvement of the dog's quality of life, although some
dogs still require ongoing treatment for lens-induced uveitis.

SUMMARY OF KEY POINTS

Most diabetic dogs seem to have a late-onset form of type 1 diabetes

analogous to latent autoimmune diabetes of adults in human beings,
which is characterized by absolute insulin deficiency. The three goals of
therapy for diabetic dogs are resolution of all clinical signs, avoidance
of insulin-induced hypoglycemia, and resumption of their usual lifestyle
and exercise level. Hypoglycemia is best avoided by adopting a conser-
vative approach to insulin dosing and a twice-daily dosing regimen.
Good glycemic control is readily achieved in most diabetic dogs with
twice-daily administration of lente, NPH, or premixed combinations of
regular and NPH insulin. The diet fed should primarily be palatable
and nutritionally balanced. Good clinical control is readily achieved
with adult dog maintenance diets. Improved glycemic control may be
achieved in some diabetic dogs if the diet contains increased insoluble
fiber. Polydipsia, weight loss, lethargy, persistent negative glucosuria, or
clinical signs of hypoglycemia indicate that the diabetic dog may require
adjustment of the insulin dose. Evaluation of a serial blood glucose
curve is required to determine how to make the dosage adjustment.

References

1. Alejandro R, Feldman E, Shienvold FL, et a!: Advances in canine diabetes mellitus

research: Etiopathology and results of islet transplantation. JAVMA 193:1050, 1988
2. Anderson JW, Akanji AO: Dietary fiber-an overview. Diabetes Care 14:1126, 1991
3. Anderson NV, Strafuss AC: Pancreatic disease in dogs and cats. JAVMA 159:885, 1971
4. Bagley LHn, Lavach JD: Comparison of postoperative phacoemulsification results in
dogs with and without diabetes mellitus: 153 cases (1991-1992). JAVMA 205:1165, 1994
5. Beam S, Correa MT, Davidson MG: A retrospective-cohort study on the development
of cataracts in dogs with diabetes mellitus: 200 cases. Vet Ophthalmol 2:169, 1999
 MANAGEMENT OF CANINE DIABETES 877

6. Besch W, Woltanski KP, Fischer U, et al: Measurement of plasma canine C-peptide by

radioimmunoassay. Exp Clin Endocrinol Diabetes 86:146, 1985
7. Blaxter AC, Cripps PJ, Gruffydd-Jones TJ: Dietary fibre and post prandial hypergly-
caemia in normal and diabetic dogs. J Small Anim Pract 31:229, 1990
8. Bolli GB: Counterregulatory mechanisms to insulin-induced hypoglycemia in hu-
mans: Relevance to the problem of intensive treatment of IDDM. J Pediatr Endocrinol
Metab 11:103, 1998
9. Bottini P, Boschetti E, Pampanelli S, et al: Contribution of autonomic neuropathy to
reduced plasma adrenaline responses to hypoglycemia in IDDM: Evidence for a
nonselective defect. Diabetes 46:814, 1997
10. Briggs C, Nelson R, Feldman E, et al: Serum fructosamine for monitoring glycemic
control of diabetic dogs [abstract]. J Vet Intern Med 12:211, 1998
11. Briggs CE, Nelson RW, Feldman EC, et al: Reliability of history and physical examina-
tion findings for assessing control of glycemia in dogs with diabetes mellitus: 53
cases (1995-1998). JAVMA 217:48, 2000
12. Casella M, Reusch CE: Home monitoring of capillary blood glucose in dogs and cats:
Technical aspects [abstract]. J Vet Intern Med 14:377, 2000
13. Church DB: The blood glucose response to three prolonged duration insulins in
canine diabetes mellitus. J Small Anim Pract 22:301, 1981
14. Church DB: Canine diabetes mellitus: Some therapeutic considerations. In Grunsell
GSG, Hill FWG (eds): Veterinary Annual, ed 22. Bristol, Scientechnica, 1982, p 235
15. Church DB: Treating the complicated diabetic patient. In Proceedings of the 24th
Annual Conference of the Australian Small Animal Veterinary Association, Alice
Springs, Australia, 1997, p 142
16. Cohn LA, McCaw DL, Tate DJ, et al: Assessment of five portable blood glucose
meters, a point-of-care analyzer, and color test strips for measuring blood glucose
concentration in dogs. JAVMA 216:198, 2000
17. Concannon PW: Canine pregnancy and parturition. Vet Clin North Am Small Anim
Pract 16:453, 1986
18. Concannon PW, McCann JP, Temple M: Biology and endocrinology of ovulation,
pregnancy and parturition in the dog. J Reprod Fertil Suppl 39:3, 1989
19. Cotton RB, Cornelius LM, Theran P: Diabetes mellitus in the dog: A clinicopathologic
study JAVMA 159:863, 1971
20. Dixon JB, Sanford J: Pathological features of spontaneous canine diabetes mellitus. J
Comp Pathol 72:153, 1962
21. Duesberg C, Havel P, Elliott E, et al: Impaired counterregulatory response to insulin-
induced hypoglycemia in diabetic dogs [abstract]. J Vet Intern Med 9:181, 1995
22. Eigenmann JE, Eigenmann RY, Rijnberk A, et al: Progesterone-controlled growth
hormone overproduction and naturally occurring canine diabetes and acromegaly.
Acta Endocrinol 104:167, 1983
23. Elie M, Hoenig M: Canine immune mediated diabetes mellitus: A case report. J Am
Anim Hosp Assoc 31:295, 1995
24. Elliott DA, Nelson RW, Feldman EC, et al: Glycosylated hemoglobin concentrations
in the blood of healthy dogs and dogs with naturally developing diabetes mellitus,
pancreatic 13-cell neoplasia, hyperadrenocorticism, and anemia. JAVMA 211:723, 1997
25. Feldman EC, Nelson RW: Diabetes mellitus. In Canine and Feline Endocrinology and
Reproduction. Philadelphia, WB Saunders Company, 1996, p 339
26. Feldman EC, Nelson RW: Diabetic ketoacidosis. In Canine and Feline Endocrinology
and Reproduction. Philadelphia, WB Saunders Company, 1996, p 392
27. Feldman EC, Nelson RW: Ovarian cycle and vaginal cytology. In Canine and Feline
Endocrinology and Reproduction. Philadelphia, WB Saunders Company, 1996, p 526
28. Feldman EC, Nelson RW, Karam JH: Reduced immunogenicity of pork insulin in dogs
with spontaneous insulin-dependent diabetes mellitus (IDDM) [abstract]. Diabetes
32:153A, 1983
29. Fischer U, Besch W, Freyse EJ: Canine C-peptide for characterisation of experimental
diabetes in dogs. Endocrinol Exp 19:139, 1985
29a. Fleeman LM, Rand JS: Comparison of serial blood glucose curves performed on
consecutive days in diabetic dogs [abstract]. J Vet Intern Med 15:297, 2001
878 FLEEMAN & RAND

30. Fleeman LM, Rand JS: The behavioral responses of pet dogs to capillary blood glucose
testing [abstract]. J Vet Intern Med 14:343, 2000
31. Fleeman LM, Rand JS: Efficacy of intermittent low-dose heparinised saline flushes for
maintaining indwelling peripheral and central catheters in diabetic dogs [abstract].
In Proceedings of the WSAVA/FECAVA World Congress, Amsterdam, 2000, p 516
32. Fleeman LM, Rand JS: Efficacy of intermittent low-dose heparinised saline flushes for
maintaining indwelling peripheral and central intravenous catheters in diabetic dogs.
Aust Vet Pract, in press
33. Fleeman LM, Rand JS: Long-term management of the diabetic dog. Waltham Focus
10:16, 2000
34. Ford SL, Nelson RW, Feldman EC, et al: Insulin resistance in three dogs with
hypothyroidism and diabetes mellitus. JAVMA 202:1478, 1993
35. Forrester SD, Troy GC, Dalton N, et al: Retrospective evaluation of urinary tract
infection in 42 dogs with hyperadrenocorticism or diabetes mellitus or both. J Vet
Intern Med 13:557, 1999
36. Freiherr von Bolcshazy G: Examination of immune reaction due to use of swine
insulin in diabetic dogs [abstract]. In Proceedings of the World Small Animal Veteri-
nary Association Conference, Lyon, 1999
37. Fritsche A, Stumvoll M, Grub M, et al: Effect of hypoglycemia on 13-adrenergic
sensitivity in normal and type 1 diabetic subjects. Diabetes Care 21:1505, 1998
38. Gershwin LJ: Familial canine diabetes mellitus. JAVMA 167:479, 1975
39. Graham PA, Nash AS: The critical evaluation of tests for monitoring glycemic control
in canine diabetes mellitus [abstract]. J Vet Intern Med 11:123, 1997
40. Graham PA, Nash AS: Rates of blindness and other complications in diabetic dogs
[abstract]. J Vet Intern Med 11:124, 1997
41. Graham PA, Nash AS: Survival data analysis applied to canine diabetes mellitus
[abstract]. J Vet Intern Med 11:142, 1997
42. Graham PA, Maskell IE, Nash AS: Canned high fiber diet and postprandial glycemia
in dogs with naturally occurring diabetes mellitus. J Nutr 124:2712S, 1994
43. Haines DM: A re-examination of islet cell cytoplasmic antibodies in diabetic dogs.
Vet Immunol Immunopathol 11:225, 1986
44. Harb-Hauser M, Nelson R, Gershwin L, et al: Prevalence of insulin antibodies in
diabetic dogs [abstract]. In Proceedings of the 16th American College of Veterinary
Internal Medicine Forum, San Diego, 1997, p 703
45. Hess RS, Ward CR: Effect of insulin dosage on glycemic response in dogs with
diabetes mellitus: 221 cases (1993-1998). JAVMA 216:217, 2000
46. Hess RS, Kass PH, Ward CR: Breed distribution of dogs with diabetes mellitus
admitted to a tertiary care facility. JAVMA 216:1414, 2000
47. Hoenig M, Dawe DL: A qualitative assay for beta cell antibodies. Preliminary results
in dogs with diabetes mellitus. Vet Immunol Immunopathol 32:195, 1992
48. Imamura T, Koffler M, Helderman JH, et al: Severe diabetes induced in subtotally
depancreatized dogs by sustained hyperglycemia. Diabetes 37:600, 1988
49. Jensen AL: Glycated blood proteins in canine diabetes mellitus. Vet Rec 137:401, 1995
50. Jensen AL: Various protein and albumin corrections of the serum fructosamine con-
centration in the diagnosis of canine diabetes mellitus. Vet Res Commun 17:13, 1993
51. Johnston SD: Diagnostic and therapeutic approach to infertility in the bitch. JAVMA
176:1335, 1980
52. Karamanos B: The dietary management of diabetes. In Dialogue Diabetes Literature
Review Service. Courbevoie Cedex, France, Servier International, 1998, p 11
53. Kawanishi K, Nishina Y, Ishida T, et al: Immunoreactive dog C-peptide level in the
pancreatic vein. Horm Metab Res 12:660, 1980
54. Kimmel S, Ward C Henthorn P, et al: Familial insulin-dependent diabetes mellitus in
Samoyed dogs [abstract]. J Vet Intern Med 13:177, 1999
55. Kimmel SE, Michel KE, Hess RS, et al: Effects of insoluble and soluble dietary fiber
on glycemic control in dogs with naturally occurring insulin-dependent diabetes
mellitus. JAVMA 216:1076, 2000
56. Korytkowski MT, Mokan M, Veneman TF, et al: Reduced 13-adrenergic sensitivity
in patients with type 1 diabetes and hypoglycemia unawareness. Diabetes Care
21:1939, 1998
 MANAGEMENT OF CANINE DIABETES 879

57. Kramer JW: Inherited, early-onset, insulin-requiring diabetes mellitus in Keeshond

dogs. Am J Pathol 105:194, 1981
58. Lafrance L, Rabases-Lhoret R, Poisson D, et al: Effects of different glycaemic index
foods and dietary fibre intake on glycaemic control in type 1 diabetic patients on
intensive insulin therapy. Diabet Med 15:972, 1998
59. Ling GV, Lowenstine LJ, Pulley T, et al: Diabetes mellitus in dogs: A review of
initial evaluation, immediate and long-term management, and outcome. JAVMA
170:521, 1977
60. Marca MC, Loste A, Unzueta A, et al: Blood glycated hemoglobin evaluation in sick
dogs. Can J Vet Res 64:141, 2000
61. Marmor M, Willeberg P, Glickman LT, et al: Epizootiologic patterns of diabetes
mellitus in dogs. Am J Vet Res 43:465, 1982
62. Matsuhisa M, Shi ZQ, Wan C, et al: The effect of pioglitazone on hepatic glucose
uptake measured with indirect and direct methods in alloxan-induced diabetic dogs.
Diabetes 46:224, 1997
63. Mattheeuws D, Rottiers R, Kaneko JJ, et al: Diabetes mellitus in dogs: Relationship of
obesity to glucose tolerance and insulin response. Am J Vet Res 45:98, 1984
64. McCann JP, Concannon PW: Effects of sex, ovarian cycles, pregnancy and lactation
on insulin and glucose response to exogenous glucose and glucagon in dogs [abstract].
Biol Reprod 28:41, 1983
65. Mokan M, Mitrakou A, Veneman T, et al: Hypoglycemia unawareness in IDDM.
Diabetes Care 17:1397, 1994
66. Montgomery TM, Nelson RW, Feldman EC, et al: Basal and glucagon-stimulated
plasma C-peptide concentrations in healthy dogs, dogs with diabetes mellitus, and
dogs with hyperadrenocorticism. J Vet Intern Med 10:116, 1996
67. Nelson R, Briggs C, Scott-Moncrieff JC, et al: Effect of dietary fiber type and quantity
on control of glycemia in diabetic dogs [abstract]. In Proceedings of the 18th American
College of Veterinary Internal Medicine Forum, Seattle, 2000, p 753
68. Nelson RW, Duesberg CA, Ford SL, et al: Effect of dietary insoluble fiber on control
of glycaemia in dogs with naturally acquired diabetes mellitus. JAVMA 212:380, 1998
69. Nelson RW, Robertson J, Feldman EC, et al: Effect of the a-glucosidase inhibitor
acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus.
JAVMA 216:1265, 2000
70. Nelson RW, Ihle SL, Lewis LD, et al: Effects of dietary fiber supplementation on
glycemic control in dogs with alloxan-induced diabetes mellitus. Am J Vet Res
52:2060, 1991
71. Neubauer HP, Schone HH: The immunogenicity of different insulins in several animal
species. Diabetes 27:8, 1978
72. Peterson ME: Decreased insulin sensitivity and glucose tolerance in spontaneous
canine hyperadrenocorticism. Res Vet Sci 36:177, 1984
73. Polonsky K, Jaspan J, Pugh W, et al: Metabolism of C-peptide in the dog. In vivo
demonstration of the absence of hepatic extraction. J Clin Invest 72:1114, 1983
74. Porksen NK, Munn SR, Steers JL, et al: Mechanisms of sulfonylurea's stimulation of
insulin secretion in vivo: Selective amplification of insulin secretory burst mass.
Diabetes 45:1792, 1996
75. Rand JS, Link KR: Glucose toxicity: Its pathogenesis and clinical significance. In
Proceedings of the 13th American College of Veterinary Internal Medicine Forum,
Lake Buena Vista, 1995, p 144
76. Robertson J, Nelson RW, Kass P, et al: Effects of the a-glucosidase inhibitor acarbose,
on postprandial serum glucose and insulin concentrations in healthy dogs. Am J Vet
Res 60:541, 1999
77. Rubenstein AH, Kuzuya H, Horwitz DL: Clinical significance of circulating C-peptide
in diabetes mellitus and hypoglycaernic disorders. Arch Intern Med 137:625, 1977
78. Sai P, Debray-Sachs M, Jondet A, et al: Anti-beta-cell immunity in insulinopenic
diabetic dogs. Diabetes 33:135, 1984
79. Salgado D, Reusch C, Spiess B: Diabetic cataracts: Different incidence between dogs
and cats. Schweiz Arch Tierheilkd 142:349, 2000
80. Scaramal JD, Renauld A, Gomez NV, et al: Natural estrous cycle in normal and
diabetic bitches in relation to glucose and insulin tests. Medicina (Buenos Aires)
57:169, 1997
880 FLEEMAN & RAND

81. Schachter S, Nelson RW, Kirk C: Effect of oral chromium picolinate on glycemic
control in insulin-treated diabetic dogs [abstract]. JVet Intern Med 14:345, 2000
82. Selman PJ, Mol JA, Rutteman GR, et a!: Progestin treatment in the dog I. Effects on
growth hormone, insulin-like growth factor I and glucose homeostasis. Eur JEndocri-
nol 131:413, 1994
83. Simpson KW: Current concepts of the pathogenesis and pathophysiology of acute
pancreatitis in the dog and cat. Compend Contin Educ Pract Vet 15:247, 1993
84. Soon-Shiong P, Feldman E, Nelson R, et a!: Successful reversal of spontaneous diabe-
tes in dogs by intraperitoneal microencapsulated islets. Transplantation 54:769, 1992
85. Spears JW, Brown TT, Sunvold GD, et al: Influence of chromium on glucose metabo-
lism and insulin sensitivity. In Reinhart GA, Carey DP (eds): Recent Advances in
Canine and Feline Nutrition, vol II. 1998 lAMS Nutrition Symposium Proceedings.
Wilmington, DE, Orange Frazer Press, 1998, p 103
86. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus:
Report of the Expert Committee on the Diagnosis and Classification of Diabetes
Mellitus. Diabetes Care 20:1183, 1997
87. Thoresen SI, Lorenzen FH: Treatment of diabetes mellitus in dogs using isophane
insulin penfills and the use of serum fructosamine assays to diagnose and monitor
the disease. Acta Vet Scand 38:137, 1997
88. Truett AA, Borne AT, Monteiro MP, et a!: Composition of dietary fat affects blood
pressure and insulin responses to dietary obesity in the dog. Obes Res 6:137, 1998
89. van Keulen LJ, Wesdorp JL, Kooistra HS: Diabetes mellitus in a dog with a growth
hormone-producing acidophilic adenoma of the adenohypophysis. Vet Pathol
33:451, 1996
90. Veneman T, Mitrakou A, Mokan M, et a!: Induction of hypoglycemia unawareness
by asymptomatic nocturnal hypoglycemia. Diabetes 42:1233, 1993
91. Wess G, Reusch C: Capillary blood sampling from the ear of dogs and cats and use
of portable meters to measure glucose concentration. J Small Anim Pract 41:60, 2000
92. Wess G, Reusch C: Evaluation of five portable blood glucose meters for use in dogs.
JAVMA 216:203, 2000
93. Whitley NT, Drobatz KJ, Panciera DL: Insulin overdose in dogs and cats: 28 cases
(1986-1993). JAVMA 211:326, 1997
94. Williams DA: Diagnosis and management of pancreatitis. J Small Anim Pract 35:445,
1994
95. Williams DA: Exocrine pancreatic disease. In Ettinger SJ, Feldman EC (eds): Textbook
of Veterinary Internal Medicine. Philadelphia, WB Saunders, 1995, p 1372
96. Wolfsheimer KJ, Peterson ME: Erythrocyte insulin receptors in dogs with spontaneous
hyperadrenocorticism. Am J Vet Res 52:917, 1991
97. Zimmet PZ, Tuomi T, Mackay IR, et al: Latent autoimmune diabetes mellitus in
adults (LADA): The role of antibodies to glutamic acid decarboxylase in diagnosis
and prediction of insulin dependency. Diabet Med 11:299, 1994

Address reprint requests to

Linda M. Fleeman, BVSc, MACVSc
Companion Animal Sciences
The University of Queensland
St Lucia, QLD 4072
Australia