Journal of Feline Medicine and Surgery (2001) 3, 99103

doi:10.1053/jfms.2001.0123, available online at http://www.idealibrary.com on

PROCEEDINGS OF ESFM SYMPOSIUM AT BSAVA CONGRESS
2001
What is so special about feline diabetes mellitus?
Dr Carole A Zerbe
University of Pennsylvania, USA 2001 European Society of Feline Medicine
C
ats differ from the dog and other species
in many ways. For example, diabetes
mellitus (DM) as a syndrome in the cat
has several notable differences from the dog. This
manuscript will address some of the ways in
which feline DM differs from canine DM or is
otherwise unique.
Classication of DM in the cat
The two major classications of DM are type 1,
also known as IDDM (insulin dependent DM),
juvenile onset DM, or non-ketosis prone DM,
and type 2 or NIDDM (non-insulin dependent
DM), adult onset DM, or ketosis prone DM. Type
1 DM refers to a diabetic state brought about
because of a loss of insulin production and
secretion by the -islet cells. Because these
patients are insulinopenic they require insulin
injections as part of their treatment. Type 2 DM
refers to a diabetic state brought about because
of insulin resistance, generally through a loss of
insulin receptor numbers or affinity. This renders
the insulin that diabetics do have less effective
and, at least initially, these patients have hyper-
insulinemia as well as hyperglycaemia. Treat-
ment for these patients focuses on increasing the
efficiency of insulin utilisation and production.
Additionally, type 2 DM can progress to type
1 DM.
In people type 2 is the most common cause of
DM, whereas our small animal patients usually
have type 1 DM. In dogs DM is almost exclu-
sively type 1, with rare cases of type 2. In
contrast, the cat has a much higher (at least 20%)
incidence of type 2 DM. The actual incidence of
type 2 DM in the cat is unknown and is contro-
versial. The author believes that, in the cat type 1
(IDDM) is the most common classication of
DM, however, a signicant percentage of cats do
have type 2 (NIDDM). Other authors believe
type 2 DM is the most common form of the
disease in the cat. Irrespective of what percent-
age of diabetic cats have type 2 diabetes, this
issue is major and relates directly to the many
other differences between diabetic cats and dogs
as noted below.
Our clients, being people are most familiar
with type 2 DM and therefore often inquire
about treatment with diet, exercise, and pills
(oral hypoglycaemics). As veterinary prac-
titioners our clinical experience for treatment
revolves around insulin usage, because our
patients are usually type 1 diabetics. This differ-
ence is important to make clear for the client.
That being said, the type 2 feline diabetic patient
raises some interesting possibilities with regard
to alternative treatments, treatment outcomes,
and etiology.
Etiology of DM
The cause of DM is multifactorial and is perhaps
better dened in people than the cat or dog.
Nevertheless, pathology of the pancreas of small
animals is variable and undoubtedly reects the
multifactorial etiology of DM. In the pancreas of
diabetic cats, islet-specic amyloidosis, -cell
vacuolation and degeneration, are often noted.
However, other cats do not have any of these
changes but instead have a reduction in the
number of pancreatic islets and/or insulin con-
taining cells. Pancreatitis, though previously
1098-612X/01/020099+05 $35.00/0 2001 European Society of Feline Medicine
thought to be uncommon in the cat, was found in
51% of diabetic cats at the time of necropsy in one
study. The principle constituent of amyloid iso-
lated from the pancreatic tissue of humans and
cats is islet-amyloid polypeptide (IAPP), or amy-
lin. IAPP has been identied within -cell secre-
tory granules of both species and is co-released
with insulin. Evidence suggests that IAPP can
antagonise insulin actions and therefore itself
might be hypersecreted in NIDDM. In this way it
may contribute to progression of type 1 DM
In contrast dogs have very little if any amyloid
deposition in the islets. Genetic predispositions
have been suggested through familial associ-
ations and by pedigree analysis of Keeshonds.
Environmental factors such as viral infections,
chemicals, and chronically stressful situations
may also have a role in etiology of DM. Other
important considerations are immune-mediated
destruction of the islets as well as pancreatitis
The following table indicating possible causes
of DM in cats and dogs helps to emphasis the
difference between the two species as well as the
multifactorial etiology of this disease (from
Feldman EC, Nelson RW (1996) Diabetes
mellitus. In: Canine and feline endocrinology and
reproduction. 2nd ed. Feldman EC and Nelson
RW (eds): Philadelphia, WB Saunders, p 340).
Signalment
This is a disease of middle-aged to older cats.
While there are no reported breed dispositions,
males are about two times more commonly
affected than are females. In contrast, some dog
breeds are over represented (Keeshonds, Pulik,
Carin Terriers, and Miniature Pinchers) or
under represented (Cocker Spaniels, German
Shepherds, Collies, Pekingese, Rottweilers, and
Boxers) and the disease occurs more frequently
in females.
What is glucose toxicity?
The phenomenon of glucose toxicity (GT) is
important for the veterinarian to understand and
makes for a better understanding of DM in the
cat. In the face of chronic hyperglycaemia, -islet
cells down regulate insulin secretion. In other
words in response to hyperglycaemia the islet
cells lose their ability to produce and secrete
insulin, and DM results. Fortunately this toxicity,
if caught early enough, is reversible and with
correction of hyperglycaemia to euglycaemia
normal insulin secretion can be restored. This is
in contrast to dogs where a phenomenon of -cell
burnout (exhaustion) is more likely to occur. In
this situation, as the -cells are stimulated to
secrete more and more insulin, they become
exhausted and permanently lose their ability to
secrete insulin. Therefore even when euglycae-
mia can be restored in the dog, the pancreas will
usually not regain its ability to produce and
secrete insulin. In this case DM is permanent and
insulin dependent (type 1).
This glucose-induced, sometimes reversible,
insulinopenia is responsible in large part for
difficulties in distinguishing type 1 from type
2 DM in the cat. With type 1 DM, measurement
of insulin should reect a decient or undetect-
able amount. With type 2 DM insulin concen-
trations are expected to be increased but may be
normal or low. Because of glucose toxicity, in the
cat, both type 1 and 2 would have insulinopenia,
thus, distinguishing between the two is difficult
prospectively. Glucose toxicity may, in part,
explain some cases of transient DM.
Transient DM in cats: How do we manage it?
Can we predict which cats will experience it?
The exact incidence of transient DM in the cat is
unknown but is usually estimated at or below
20%. It is an important issue from three perspec-
tives: rst, it may inuence the clients decision
to pursue therapy, it may inuence the course of
treatment, and lastly, when cats lose their need
for insulin (ie regain the ability of the pancreas to
secrete insulin), the risk of hypoglycaemia is
greatly increased.
Some clients that would otherwise consider
euthanasia for their cat, may move forward with
treatment of DM (understanding that the need
for treatment may disappear), and discover that
Potential factors involved in the etiopathogenesis of
diabetes mellitus
Dog Cat
Genetics Islet amyloidosis
Immune-mediated insulitis Obesity
Pancreatitis Infection
Obesity Concurrent illness
Infection Drugs
Concurrent illness Pancreatitis
Drug Genetics (?)
Islet amyloidosis (?) Immune-mediated
insulitis (?)
100 CA Zerbe
it is not so hard to manage DM after all. The
possibility of transient diabetes in the patient
may inuence whether insulin or oral hypo-
glycaemics are used for initial treatment. It is
important that owners periodically monitor urine
glucoses or that glucose curves be done because
cats may lose their need for insulin (unknown
to the owner who continues insulin therapy) and
develop severe or fatal hypoglycaemia (see later
section hypoglycaemia unawareness).
Cats with type 2 DM would be most likely to
have transient DM but it can be impossible to
distinguish type 1 from type 2 DM in the cat.
Candidates include obese cats, cats receiving
progestages or steroids, and cats with hyper-
adrenocorticism. As obese cats lose weight in
concert with adequate glycaemic control glucose
toxicity would be reversed and insulin secretion
restored. Care must always be taken in cats with
weight reduction because hepatic lipidosis is
common. The author usually recommends that
the owner spot check urine glucose at home and
call if there is a decreasing trend in urine glucose
concentration or a negative result. In this way
impending hypoglycaemia is adverted.
In contrast to the cat, DM is very rarely revers-
ible in the dog. The circumstances are usually
secondary to increased progesterone. In the dog
progesterone induces an increase in growth hor-
mone secretion. Growth hormone is diabetogenic
and in excess can lead to DM. If caught early
enough (before pancreatic -cell exhaustion) this
DM is easily reversed. It is often characterised
by high insulin requirements and no ketosis.
Progesterone may be increased iatrogenically
through treatment with drugs to prevent
oestrous or to modify behaviour. Another situ-
ation occurs in intact bitches during the long
diestrous phase that is characterised by high
progesterone. Treatment is accomplished by
reducing progesterone (thereby GH) with ovari-
oysterectomy or drug withdrawal. An important
part of treatment however is preventing hypo-
glycaemia that quickly results.
Why do we consider use of oral
hypoglycaemics in cats but not dogs? Do they
really work?
Usually when we think of oral hypoglycaemic
drugs in veterinary medicine we think of the
sulfonylurea, glipizide. The drug works primar-
ily by increasing pancreatic insulin secretion and
enhancing -cell responsiveness to glucose.
Therefore, glipizide will not work in type 1
diabetics (remember in type 1 diabetics, the
pancreas cannot produce insulin). It is only
the population of type 2 diabetics that might
respond to treatment with glipizide. However,
as previously noted, it can be impossible to
distinguish type 1 from type 2 DM in the cat.
Other classes of oral hypoglycaemics are com-
monly used in humans but experience with them
in the cat is limited. Clearly further investigation
is warranted and these other drugs are discussed
below.
Published success with glipizide use in
diabetic cats varies. A preliminary study of 20
cats with DM revealed a long-term response rate
of 55%. Thirteen cats (65%) initially had a com-
plete or partial response. Seven cats (35%) did
not respond. Results from a larger more recent
study showed less success with glipizide treat-
ment. Of the 50 cats, seven (14%) responded
completely, six (12%) were transiently diabetic,
and 28 (56%) had no response. Three cats had an
initial but not continued response. Long-term
response rate was about 38%. A larger retrospec-
tive study of 104 cats had a long-term response
rate of about 35%.
Side effects of glipizide administration include
vomiting that is usually transient (15%),
increased liver enzymes and icterus (10%), and
hypoglycaemia (1215%). Glipizide may eventu-
ally lose it effectiveness over time working for
only days to several years. The true incidence of
long-term success in the stable feline diabetic
population is unknown as is the true incidence
of eventual loss of efficacy of glipizide over time.
Generally, unstable diabetics or those with con-
current illnesses are not good candidates for
treatment with glipizide. The reader is referred
elsewhere for treatment schedules and drug
dosages.
Diet and exercise. How do I do that?
Diet and exercise may have a profound effect on
glycaemic control. However, putting a diabetic
cat on a diet, or even feeding them on a strict
schedule, is easier said than done! There are
several things to consider: (1) hepatic lipidosis,
(2) monster cat syndrome, (3) hypoglycaemia,
(4) bre, carbohydrate and protein content of the
diet, and (5) use of timed feeders or ad lib
feeding.
Hepatic lipidosis is always a concern with
weight reduction in an obese cat. To initiate
weight loss in these patients, caloric intake
should be limited to 70 to 75% of the energy
What is so special about feline diabetes mellitus? 101
needs for the cats optimum weight. If weight
loss is not needed then diets fed at a maintenance
level of 6070 kcal/kg/day are adequate.
Monster cat syndrome is the authors descrip-
tion of those cats that develop major behavioural
problems in response to decreased feeding.
Owner complaints range from stealing food from
the garbage, cupboard, or your hand youd be
amazed how quickly even an obese cat can
move cats that nip at their owners ankles and
deant behaviour such as urinating and defecat-
ing on the bed, or any other inappropriate place.
It seems as though some cats need to eat and/or
have their stomachs full. Treats that the author
has successfully used are carrots and string
beans (frozen vegetables that were thawed).
Even though cats are obligate carnivores, many
cats will eat these high bre, low calorie snacks.
Benets are improved behaviour and owner-pet
relationship, continued weight loss, and by
virtue of this weight loss, and perhaps even the
increase of bre in the diet, better glycaemic
control.
Weight loss generally necessitates a reduction
in insulin dosage. This is because of a reduction
in calories consumed as well as decreased insulin
resistance. Remember that obese diabetic cats
may be type 2 diabetics or possibly transient
diabetics so you want to plan for decreased
insulin requirements. Have the owners measure
periodic urine glucoses at home and/or perform
glucose curves.
As far as the specic diet is concerned bre,
carbohydrate and protein requirements/
recommendations for the diabetic cat are
unknown. However, special considerations
for this species include: the cat is an obligate
carnivore, protein rather than carbohydrates
stimulate insulin release, and glucose require-
ments are maintained from protein precursors
(gluconeogenesis) rather than carbohydrate
sources. Current dietary recommendations
are for a low-carbohydrate, high protein diet.
Increased bre content may also be helpful.
Ideal feeding schedules for animals receiving
twice a day insulin treatments would involve
QID feedings, that is a meal before each insulin
injection and one in the mid-afternoon and
late evening. Of course there are alternatives
when owners are unable/unwilling to adhere
to this schedule. For example, one could use
commercially available timed feeders, or if the
cat is a nibbler, feed ad lib.
As for increasing exercise; going for a run or
walk, throwing a ball in the park, or stick in the
lake just isnt going to do the trick! But nd the
pets favourite fascination and see what is poss-
ible. For example, the authors personal favourite
for her cat is the laser light (that way her cat,
Sabs, can play while she rests in a chair). Another
trick for the polyphagic cat is to hide treats
in play toys or in hard-to-reach places so that
exercise is required to obtain the food.
Are their any other treatments that
veterinarians can offer feline pet owners?
Yes, but the veterinarian should proceed
cautiously as experiences with these modalities
are limited and should only be used as adjunc-
tive therapy. There are no substitutes for insulin
if it is needed, but ways to improve glycaemic
control may include the following: diet, exercise,
and glipizide (covered above), or other hypogly-
caemic agents that act to inhibit hepatic glucose
production, diminish absorption of glucose from
the intestine, or act as insulin-sensitising agents.
Metformin, an agent that inhibits hepatic
glucose output, has been associated with severe
side effects when initially used in cats. However,
it may be safe and effective when used in cats at
lower doses. A published dose for the cat is
210 mg/kg given twice daily.
Acarbose, a drug that impairs glucose absorp-
tion from the intestine, is an alpha-glucosidase
inhibitor. It decreases bre digestion and conse-
quently glucose production from the food. A
published dose for the cat is 12.525 mg with
meals. Side effects are more commonly noted at
the higher dose and include semi-formed stool
and diarrhoea. This drug should not be used
alone or in normal or under weight cats.
Three insulin-sensitising agents have been
used in the cat. One drug, a new class of oral
hypoglycaemics that held promise for use in
human type 2 diabetics, has recently been dis-
continued because of idiosyncratic hepato-
toxicity (troglitazone). The transition metals
vanadium and chromium are gaining renewed
popularity in human medicine and are now
being investigated for use in the cat. These
metals are insulinomimetic or insulin-sensitising
agents that work by bypassing the insulin
receptor to directly stimulate glucose metabolism
by the cell. This is an ideal adjunctive treatment
for type 2 diabetics because these patients have
decreased receptor numbers and or receptor
afnity for insulin.
Studies have been done using vanadium in
healthy or diabetic cats. Low doses of oral
102 CA Zerbe
vanadium decreased blood glucose concen-
trations and alleviated clinical signs of DM in
early type 2 diabetic cats. Serum fructosamine
concentrations were also decreased compared to
a placebo group. Side-affects include anorexia
and vomiting initially but usually resolve after
reinstitution of the vanadium therapy. Although
a dose has been published for the use of
chromium picolinate in the cat (200 mg/cat q
24 h in food), there are no published reports to
substantiate its toxicity or efficacy.
When is glucosuria and hyperglycaemia not
diagnostic for DM?
Epinephrine induced stress hyperglycaemia is
common in the cat and can rise high enough to
spill into the urine (vs glucocorticoid induced
changes which are more common in the dog).
Therefore, determination of DM in a cat may be
difficult. When the diagnosis is questionable
owners should follow urine glucoses at home in
the pets familiar environment.
Diabetic neuropathy
Peripheral neuropathy is a well-recognised com-
plication of feline and human diabetes mellitus,
but is very uncommon in the dog. The peripheral
neuropathy usually involves the distal limbs
with about 8% of diabetic cats having the classic
clinical signs of plantigrade stance, progressive
paraparesis, distal limb atrophy and pelvic limb
hyporeexia. Thoracic limb involvement is rare
but may occur. Less severe clinical signs prob-
ably have a higher incidence of occurrence but
may be detected through careful history and
through physical examination. For example, the
cat may have difficulty in jumping, pelvic limb
abduction, distal weakness while standing, and
inability to fully retract their claws.
Diagnosis is intuitive but may be conrmed
with electrophysiology and peripheral nerve and
muscle biopsy. Electrophysiological testing often
reveals prominent demyelination at all levels of
motor and sensory peripheral nerves and their
corresponding nerve roots. There was splitting
and ballooning of the myelin sheath noted
on histopathology on nerve biopsies, while
muscle biopsies had changes in both bre types
that were consistent with mild denervation.
Thus demyelination appears to be the major
peripheral nerve abnormality.
There is no specic treatment for this neuro-
pathy except to more closely regulate the DM.
Even if this is possible, improvement in periph-
eral nerve function will take several weeks to
months, and rarely is complete.
Hypoglycaemia unawareness
This refers to a phenomenon where diabetics fail
to respond physiologically to hypoglycaemia. In
other words they dont recognise the hypogly-
caemia because autonomic symptoms such as
sweating, tremor, hunger, anxiety, and palpi-
tations do not occur. Hypoglycaemia may be
immediately life threatening and the body has
many defence mechanisms to restore glucose to
normal concentrations. This response primarily
involves the counterregulatory hormones (epi-
nephrine, glucagon, glucocorticoids and growth
hormone), and a concomitant increase in the
discharge of autonomic nervous system neuro-
transmitters (norepinephrine and acetylcholine).
Hypoglycaemia unawareness is more common
in patients with frequent or persistent hypogly-
caemia, which in turn is most likely in human
diabetics when efforts are made to achieve
normal glucose concentrations. With intensive
therapy (or inappropriate therapy) and subse-
quent episodes of hypoglycaemia, there is
believed to be central nervous system adaptation.
This adaptation results in reduced counter
regulatory hormone responses (eg, increased
sensitivity to insulin) as well as diminished auto-
nomic neurotransmitter release (eg, hypogly-
caemia unawareness). The author believes
this phenomenon occurs in our small animal
practices and that it seems to be a much more
common occurrence in the cat than dog.
What is so special about feline diabetes mellitus? 103