Predi ct ors of Cl i ni cal Remi ssi on i n Cat s wi t h Di abet es Mel l i t us

E. Zini, M. Hafner, M. Osto, M. Franchini, M. Ackermann, T.A. Lutz, and C.E. Reusch
Background: Clinical remission is frequent in cats with well-controlled diabetes mellitus, but few studies explored predictors
of this phenomenon.
Hypothesis: Data retrieved from medical records at admission might be valuable to identify likelihood of remission and its
duration in diabetic cats.
Animals: Ninety cats with newly diagnosed diabetes, followed-up until death or remission.
Methods: Retrospective cohort study. Data were collected from records at admission, including history, signalment, phys-
ical examination, haematology, and biochemical prole, and the occurrence and duration of remission, dened as
normoglycemia without insulin for 4 weeks. Predictors of remission were studied with univariate and multivariate logistic
regression. Factors associated with remission duration were analyzed with Kaplan-Meier and Cox proportional hazard models.
Results: Forty-ve (50%) cats achieved remission, after a median time of 48 days (range: 8216). By study end, median
remission duration was 114 days (range: 303,370) in cats that died and 151 days (range: 281,180) in alive cats. Remission was
more likely with higher age (OR: 1.23, 95% CI: 1.041.46; P 5 .01) and less likely with increased serum cholesterol (OR: 0.36,
95%CI: 0.110.87; P 5.04). Remission was longer with higher body weight (HR: 0.65, 95%CI: 0.420.99; P 5.04) and shorter
with higher blood glucose (HR: 1.01, 95% CI: 1.001.02; P 5.02).
Conclusions and Clinical Importance: Age, body weight, cholesterol, and glucose levels are suggested for prediction of re-
mission or its duration in diabetic cats. Older cats developing diabetes may have a better outcome, possibly suggesting a slower
disease progression.
Key words: Feline; Normoglycemia; Prediction; Transient diabetes.
D
iabetes mellitus is 1 of the most commonly encoun-
tered endocrine diseases in cats.
1
Insulin therapy is
the most effective means to achieve glycemic control and
to avoid life-threatening complications in diabetic cats.
2
Interestingly, 4184% of affected cats have been reported
to maintain normoglycemia without exogenous insulin
within weeks to months of beginning therapy.
37
The term
diabetic remission or transient diabetes is used in cats
when insulin administration can be withdrawn for at least
4 consecutive weeks and when, beside restoration of nor-
mal glucose concentrations, clinical signs of diabetes have
disappeared.
5
Viability of b-cells may not have fully re-
covered, as shown by a reduced number of pancreatic islet
cells in diabetic cats examined during remission.
3
The rea-
son why remission occurs in some cats is uncertain.
Because feline b-cells are very susceptible to the detrimen-
tal effects of excess glucose,
8
it is hypothesized that an
adequate control of glycemia with insulin may reverse
glucose toxicity in the endocrine pancreas.
37
A small number of investigations addressed diabetic
remission in cats to identify predictors of this phenome-
non at the time of admission. At our institution it was
shown that serum concentrations of glucose, fructosa-
mine, insulin, glucagon, and insulin growth factor-1 are
not different between diabetic cats that achieved remis-
sion and those that did not.
4
Another group, by inducing
b-cell secretion with a glucagon stimulation test, found
similar insulin area under the curve between diabetic cats
that achieved or not remission.
3
During remission, gluc-
agon-induced insulin secretion was comparable to
healthy cats.
3
Recently, a study based on a questionnaire
to diabetic cat owners participating in an internet forum
showed that strict glycemic control, administration of
corticosteroids previous to diagnosis, and absence of
polyneuropathy were more likely in cats with remission
6
;
age, sex, body weight, renal failure, and hyperthyroidism
were not useful predictors.
6
Administration of insulin
glargine increased the chance of remission in diabetic
cats.
7
In a study, we observed that normoglycemia can
also be attained and insulin discontinued in diabetic cats
with ketoacidosis.
5
Cats with diabetes achieving remis-
sion have higher area under the curve of the glucagon-to-
insulin ratio than cats with life-long insulin requirement,
suggesting a possible role for glucagon in the pathogen-
esis of diabetic remission.
a
Improving anticipation of remission would be very
helpful to increase motivation of owners to treat their
diabetic cats. Achieving remission is advantageous
because cats benet from better quality of life and costs
of treatment are decreased. Therefore, the aim of the
present study was to explore factors that at the time of
admission might predict remission in diabetic cats;
we used data retrieved from history, signalment, physi-
cal examination, and hematology and biochemical
prole. In addition, the same factors were studied
to identify possible associations with duration of
remission.
From the Clinic for Small Animal Internal Medicine (Zini, Ha-
fner, Reusch), Institute of Veterinary Physiology (Osto, Lutz), and
the Institute of Virology (Franchini, Ackermann), Vetsuisse Faculty,
University of Zurich, 8057 Zurich, Switzerland. The study was per-
formed at the Clinic for Small Animal Internal Medicine, Vetsuisse
Faculty, University of Zurich, Switzerland.
Corresponding author: Dr Eric Zini, Clinic for Small Animal
Internal Medicine, Vetsuisse Faculty, University of Zurich, Winter-
thurerstrasse 260, 8057 Zurich, Switzerland; e-mail:
ezini@vetclinics.uzh.ch.
Submitted April 15, 2010; Revised July 1, 2010; Accepted
August 4, 2010.
Copyright r 2010 by the American College of Veterinary Internal
Medicine
10.1111/j.1939-1676.2010.0598.x
J Vet Intern Med 2010;24:13141321
Materials and Methods
Cats
Medical records of all diabetic cats admitted to the Clinic for
Small Animal Internal Medicine, Vetsuisse Faculty, University of
Zurich (Switzerland), between January 2000 and July 2009 were re-
viewed. Cats were included in the study if they had newly diagnosed
diabetes and were followed up at least until remission was achieved
or, otherwise, until death. Cats with ketoacidosis or concurrent dis-
eases were also included.
From all records, information was retrieved on admission per-
taining history (including administration of corticosteroids and
progestagens in the previous 6 months), signalment, physical exam-
ination, and blood work. Ketoacidosis or any concurrent disease
diagnosed on admission was recorded. The type of insulin adminis-
tered after discharge was also retrieved.
Whether the diabetic cat had achieved clinical remission, that is,
insulin was not required to maintain normoglycemia, and how long
remission had lasted, was obtained from follow-up records. Similar
to previous studies performed by our group, only cats that did not
need insulin for at least 4 consecutive weeks were considered in re-
mission.
5,a
As a standard procedure at our institution, all diabetic
cats had been reassessed at 1, 23, 46, 812 weeks, and 6 months
following discharge, and thereafter every 36 months, regardless of
remission. Additional evaluations had been planned according to
individual needs.
Statistical Analysis
To identify predictors of remission, univariate binary logistic re-
gression analysis was performed with all diabetic cats and the
following factors used as dichotomous variables: previous adminis-
tration of corticosteroids and progestagens, sex (male or female),
breed (pure- or cross-bred), increase of leukocyte count, serum cho-
lesterol, total protein, creatinine, urea, potassium, bilirubin and
lipase, decrease of hematocrit, serum albumin and potassium, and
presence of ketoacidosis or of concurrent disease. Increase and de-
crease of above factors was relative to reference ranges established
at our institution (Clinical Laboratory, Vetsuisse Faculty, Univer-
sity of Zurich, Switzerland). The type of insulin administered, either
porcine insulin zinc suspension
b
or insulin glargine,
c
was also in-
cluded in the analysis; cats that received 1 of the 2 insulin types but
died before discharge were not considered. Glucose and fructosa-
mine concentrations that are typically increased in untreated
diabetic cats were investigated as continuous variables. Age and
body weight were also studied as continuous variables. Factors that
at univariate analysis yielded Po.25 were further used to assess
their confounding effect with multivariate binary logistic regression.
Factors whose results were not available in more than 20% of cats
were excluded from the multivariate analysis to preserve the t of
the model.
In the group of cats that had insulin discontinued, analysis was
conducted to identify factors associated with duration of remission.
The inuence of above dichotomous variables was studied with
Kaplan-Meier product-limit followed by log rank test; only dichot-
omous variables represented by at least 10 cases in either category
were considered. The inuence of continuous variables was studied
with univariate Cox proportional hazard model. Factors with
Po.25 were further used to assess their confounding effect using
the Cox proportional hazard model. Cats in remission were cen-
sored if they were still alive by the study end.
Signicance was considered for Po.05. Statistical analysis was
conducted with software.
d,e
Results
Cats
Of 275 diabetic cats admitted during the study period,
90 met the inclusion criteria and were included in the
analysis. Forty-ve (50%) of the 90 diabetic cats
achieved remission and 45 (50%) did not.
Cats with Diabetic Remission
In the group that achieved remission, median age at
diagnosis was 12 years (range: 217). Thirty-two (71%)
cats were neutered male and 13 (29%) spayed female.
Thirty (67%) cats were cross-bred domestic short- or
longhair, and 11 (33%) were pure-bred, including 3 Per-
sian, 2 each Maine Coon and Siamese, and 1 each
Abyssinian, Birman, Burmese, and Ragdoll; breed was
not recorded in 4 cats. Median body weight was 5.2 kg
(range: 2.58.4). Corticosteroids or progestagens had
been administered to 5 cats, up to 3 months before
admission.
On admission median serum glucose was 419 mg/dL
(range: 2481,251; reference range: 90180), and
fructosamine was 588 mmol/L (range: 371984; reference
range: 200300). Ketoacidosis was diagnosed in 13
(29%) cats and concurrent diseases were documented in
20 (44%) cats, including 3 each with lung disease or sus-
pected pancreatitis, 2 each with cystitis, feline
immunodeciency virus or skin disease, and 1 each with
bone fracture, cholangiohepatitis, enteritis, hyper-
thyroidism, lymphoma, pure red cell aplasia, renal
failure, or stomatitis. The frequency of abnormal blood
results is summarized in Table 1.
After discharge, 21 (47%) cats were treated with insu-
lin glargine and 23 (53%) with porcine insulin zinc
suspension; in 1 cat the type of insulin is unknown. Ad-
ditional therapy was administered to treat concurrent
diseases (data not shown). Median time from discharge
to remission was 48 days (range: 8216); 25% of cats
achieved remission within 27 days, 75% within 102 days,
and only 1 cat after 6 months (Fig 1). By the end of the
study, median remission duration was 114 days (range:
303,370) in cats that were followed up until death (n 5
15) and 151 days (range: 281,180) in cats that were still
alive (n 530). Six of the 45 (13%) cats with remission did
not require insulin for more than 1,000 days; 1 of them
for more than 9 years. Overall, insulin therapy needed to
be resumed to control hyperglycemia in 13 (29%) cats,
including 6 of the cats that died and 7 of those that were
still alive at the study end. None of these 13 cats experi-
enced a further period of clinical remission.
Cats without Diabetic Remission
In the group that did not achieve diabetic remission,
median age at diagnosis was 11 years (range: 218); in 1
cat age was unknown. The cats consisted of 30 (67%)
neutered male and 15 (33%) spayed female. Twenty-nine
(71%) cats were domestic short- or longhair, and 12
(29%) were pure-bred, including 2 each Maine Coon and
Siamese, and 1 each Persian, Havana Brown, Birman,
1315 Remission from Diabetes in Cats
Burmese, Chartreux, Norwegian Forest, Oriental short-
hair, and Russian Blue; breed was not recorded in 4 cats.
Median body weight was 4.8 kg (range: 3.09.8); body
weight was not available in 1 cat. Corticosteroids or pro-
gestagens were administered to 5 cats and up to 4 months
before admission.
Table 1. Characteristics of diabetic cats with and without clinical remission, and univariate analysis of predictors of
diabetic remission.
Variable
a
Reference Range Cats with Remission Cats without Remission OR 95% CI P-Value
Age 1.13 0.991.28 .07
Sex
Neutered male 32 (71%) 30 (67%) 1.23 0.503.01 .65
Spayed female 13 (29%) 15 (33%)
Breed
Pure bred 11 (33%) 12 (29%) 0.89 0.342.33 .81
Cross bred 30 (67%) 29 (71%)
Body weight 0.99 0.751.30 .92
Previous administration of corticosteroids or progestagens
Yes 5 (11%) 1.00 0.273.73 .00
No 40 (89%) 40 (89%)
Hematocrit 3345%
Decreased 12 (27%) 16 (37%) 0.59 0.251.50 .23
Not decreased 33 (73%) 27 (63%)
Leukocyte count 4.612.8 10
3
/mL
Increased 22 (50%) 23 (55%) 0.83 0.351.93 .66
Not increased 22 (50%) 19 (45%)
Glucose concentration 90180 mg/dL 1.00 0.991.00 .95
Fructosamine concentration 200300 mmol/L 1.00 0.991.00 .70
Cholesterol concentration 100263 mg/dL
Increased 15 (34%) 24 (55%) 0.43 0.181.02 .05
Not increased 29 (66%) 20 (45%)
Total protein concentration 6480 g/L
Increased 10 (23%) 10 (22%) 1.03 0.382.79 .95
Not increased 34 (77%) 35 (78%)
Albumin concentration 3040 g/L
Decreased 6 (14%) 8 (18%) 0.73 0.232.31 .59
Not decreased 38 (86%) 37 (82%)
Creatinine concentration 1.11.7 mg/dL
Increased 7 (16%) 11 (25%) 0.57 0.201.63 .29
Not increased 37 (84%) 33 (75%)
Urea concentration 2135 mg/dL
Increased 12 (28%) 21 (47%) 0.43 0.181.04 .06
Not increased 32 (72%) 24 (53%)
Potassium concentration 3.85.4 mEq/L
Increased 4 (10%) 8 (18%) 0.49 0.141.76 .27
Not increased 38 (90%) 37 (82%)
Potassium concentration 3.85.4 mEq/L
Decreased 7 (17%) 11 (24%) 0.62 0.211.78 .37
Not decreased 35 (83%) 34 (76%)
Bilirubin concentration o.2 mg/dL
Increased 14 (38%) 20 (57%) 0.46 0.181.17 .10
Not increased 23 (62%) 15 (43%)
Lipase activity 826 U/L
Increased 26 (59%) 28 (65%) 0.77 0.331.85 .56
Not increased 18 (41%) 15 (35%)
Ketoacidosis
Yes 13 (29%) 17 (38%) 0.67 0.281.62 .37
No 32 (71%) 28 (62%)
Concurrent disease
Yes 20 (44%) 24 (53%) 0.70 0.311.61 .40
No 25 (56%) 21 (47%)
Type of insulin
Insulin glargine 21 (47%) 8 (31%) 2.05 0.745.71 .16
Porcine insulin zinc suspension 23 (53%) 18 (69%)
CI, condence interval; OR, odds ratio.
a
Age, body weight, glucose, and fructosamine do not have frequencies listed because analyzed as continuous variables.
1316 Zini et al
On admission median serum glucose was 436 mg/dL
(range: 243990) and fructosamine was 613 mmol/L
(range: 435968). Ketoacidosis was diagnosed in 17
(38%) cats and concurrent diseases were documented in
24 (53%) cats, including 3 each with cholangiohepatitis,
hypertrophic cardiomyopathy or lung disease, 2 each
with cystitis, renal failure, or stomatitis, and 1 each with
acromegaly, enteritis, epilepsy, histiocytosis, idiopathic
hypercalcemia, lymphoma, megacolon, skin disease, or
suspected pancreatitis (Table 1).
After discharge, 8 (31%) cats were treated with insulin
glargine and 18 (69%) with porcine insulin zinc suspen-
sion. Twelve cats received regular insulin on admission
because of ketoacidosis and did not survive to discharge.
Seven additional cats died before discharge; 3 of them
received insulin glargine, lente insulin, or regular insulin,
and 4 died previous to insulin therapy. Additional ther-
apy was administered to treat concurrent diseases.
Predictors of Diabetic Remission
Factors retrieved from medical records on admission
were studied to assess their role as predictors of diabetic
remission. By univariate logistic regression analysis,
higher age and the use of insulin glargine were more
likely in diabetic cats that achieved remission, whereas
low hematocrit and increased cholesterol, urea and
bilirubin were more likely in diabetic cats that did not
achieve remission (Table 1). Sex, breed, body weight,
administration of corticosteroids, or progestagens, leu-
kocyte count, serum glucose, fructosamine, total protein,
albumin, creatinine, potassium concentrations, lipase ac-
tivity, ketoacidosis, and concurrent diseases did not
predict remission in our population of cats.
The multivariate logistic regression model was con-
structed with the continuous variable age and the
dichotomous variables hematocrit, cholesterol, urea,
and bilirubin. Type of insulin was not included because
more than 20% of cats did not survive to discharge.
Based on multivariate analysis, age and serum choles-
terol were independent predictors of diabetic remission
(Po.05) (Table 2). In particular, increased cholesterol
decreased the chance of remission by almost 65%, and
per year of age chance of remission increased by approx-
imately 25%. Approximately 70% of cats that were older
than 12 years at diagnosis achieved diabetic remission,
less than 50% of cats that were between 10 and 12 years,
and only 3040% of cats below 9 years. The Hosmer-Lo-
meshow test was not signicant (P 5.34) suggesting t of
the multivariate model.
Factors Associated with Duration of
Diabetic Remission
Factors retrieved from medical records on admission
were investigated to assess possible associations with the
duration of diabetic remission. Results of Kaplan-Meier
analysis for dichotomous variables and of univariate Cox
proportional hazard model analysis for continuous vari-
ables are reported in Table 3; higher body weight was
associated with longer remission, whereas decreased
hematocrit, higher serum glucose concentration, and in-
creased serum lipase activity were associated with shorter
remission. Age, sex, breed, leukocyte count, serum
fructosamine, cholesterol, total protein, urea and bili-
rubin, ketoacidosis, concurrent diseases, and type of
insulin were not linked to the duration of remission. The
effects of administration of corticosteroids or pro-
gestagens and serum albumin, creatinine and potassium
were not assessed because we observed less than 10 cases
per category.
Results of the multivariate Cox proportional hazard
model constructed with the dichotomous variables hem-
atocrit and serum lipase, and the continuous variables
body weight and serum glucose are reported in Table 4.
With the adopted model, body weight and serum glucose
remained independently associated with the duration of
diabetic remission (Po.05). In particular, for a 1 kg in-
crease of body weight, duration of remission increased by
70
80
90
100
40
50
60
10
20
30
%

o
f

c
a
t
s

i
n

r
e
m
i
s
s
i
o
n
0 25 50 75 100 125 150 175 200 225 250
0
Days after diagnosis
Fig 1. Diabetic cats achieving clinical remission. Cumulative per-
centage of cats that did not require insulin to maintain
normoglycemia over time.
Table 2. Multivariate analysis of predictors of
diabetic remission.
Variable
Reference
Range
Chance of Diabetic
Remission
OR 95% CI P-Value
Age 1.23 1.041.46 .01
Hematocrit 3345%
Decreased 0.48 0.141.69 .26
Not decreased
Cholesterol concentration 100263 mg/dL
Increased 0.36 0.110.87 .04
Not increased
Urea concentration 2135 mg/dL 0.59 0.182.00 .40
Increased
Not increased
Bilirubin concentration o.2 mg/dL
Increased 0.49 0.161.47 .20
Not increased
CI, condence interval; OR, odds ratio.
1317 Remission from Diabetes in Cats
approximately 35%, and for a 1 mg/dL increase of glu-
cose in the hyperglycemic range, duration of remission
decreased by approximately 1% (Figs 2 and 3). The like-
lihood ratio test of the model yielded an overall w
2
difference signicant at Po.001, indicating that the vari-
ables accurately contributed to explaining the duration
of remission.
Discussion
In the present study 45 of 90 (50%) diabetic cats
achieved clinical remission, and the large majority of
them within 6 months from diagnosis, similar to previous
reports.
37
Despite remission being frequent in cats, few
studies investigated the factors that could predict this fa-
vorable outcome already at the time of 1st presentation
to the clinic.
37
Here, using commonly measured param-
eters retrieved on admission from history, signalment,
physical examination, hematology, and biochemical pro-
le, we identied predictors of remission and of its
duration. In particular, remission was more likely with
higher age, and less likely with elevated serum choles-
terol. Remission was longer with higher body weight,
and shorter with higher serum glucose.
Table 3. Univariate analysis of factors associated with duration of diabetic remission. The number of cats is
provided in parentheses for each variable.
Variable
a,b
Reference Range
Duration of Diabetic Remission
Median (days) HR 95% CI P-Value
Age 0.99 0.851.16 .92
Sex
Neutered male (32) 1240 1.69 0.544.87 .39
Spayed female (13) 1380
Breed
Pure-bred (11) 3370 0.34 0.101.12 .38
Cross-bred (30) 1240
Body weight 0.67 0.460.98 o.01
Hematocrit 3345%
Decreased (12) 150 3.03 1.2719.8 .02
Not decreased (33) 1380
Leukocyte count 4.612.8 10
3
/mL
Increased (22) 1240 2.17 0.806.25 .27
Not increased (22) 1380
Glucose concentration 90180 mg/dL 1.01 1.001.02 o.01
Fructosamine concentration 200300 mmol/L 1.00 0.991.00 .50
Cholesterol concentration 100263 mg/dL
Increased (15) 1020 1.81 0.686.67 .29
Not increased (29) 1380
Total protein concentration 6480 g/L n.a. 1.35 0.345.88 .64
Increased (10)
Not increased (34) 1240
Urea concentration 2135 mg/dL
Increased (12) 1240 1.20 0.394.01 .72
Not increased (32) 3370
Bilirubin concentration o.2 mg/dL
Increased (14) 1240 1.28 0.414.34 .64
Not increased (23) 1020
Lipase activity 826 U/L
Increased (17) 150 4.17 1.6116.7 .02
Not increased (27) 1020
Ketoacidosis
Yes (13) 1240 0.50 0.171.39 .27
No (32) 1020
Concurrent disease
Yes (20) 1380 1.52 0.574.35 .73
No (25) 1240
Type of insulin
Insulin glargine (21) n.a. 0.88 0.272.70 .79
Porcine insulin zinc suspension (23) 1240
CI, condence interval; HR, hazard ratio; n.a., not available.
a
Kaplan-Meier analysis is used for dichotomous variables; variables with less than 10 cases in 1 category are not assessed (ie, previous
administration of corticosteroids and progestagens, serum albumin, creatinine, and potassium).
b
Univariate Cox proportional hazard model analysis is used for continuous variables, including age, body weight, glucose, and fructosamine.
1318 Zini et al
Higher age at admission was associated with an aug-
mented chance of diabetic remission. Specically, for
each additional year of age at 1st diagnosis, remission
was 25% more likely. This nding may be unexpected
based on the notion that aging is associated with de-
creased b-cell function in different mammalian
species.
9,10
However, a study demonstrated that type 2
diabetic humans rst diagnosed after 65 years of age
present with a less severe disease course and less severe
metabolic deterioration. At baseline and during follow-
up, type 2 diabetics that were older than 65 years at di-
agnosis had lower fasting blood glucose and glycated
hemoglobin concentrations.
11
The reason why diabetes
in older humans evolves more slowly has not been clar-
ied. Also in type 1 diabetic patients, younger age at
diagnosis was associated with a faster progression to in-
sulin dependency.
12,13
It cannot be excluded that the
positive association between remission and age observed
in cats is because of owners being disposed to provide
better care in older animals.
Higher than normal cholesterol reduced the chance of
remission by almost 65% in diabetic cats. Most studies in
humans linking hyperlipidemia to type 2 diabetes had fo-
cused on the role of triglycerides and free fatty acids, but
recent in vivo studies with rodents have shown that in-
creased cholesterol concentrations can also impair b-cell
function or viability.
14,15
Further, isolated pancreatic
islets had increased content of cholesterol, and its
depletion was followed by restoration of insulin secre-
tion.
14
In another transgenic mice model characterized
by hypercholesterolemia, besides impaired insulin secre-
tion, the number and size of pancreatic islets were
reduced by more than 50%.
15
Therefore, increased se-
rum cholesterol can exert a direct toxic effect on b-cells.
It is possible that hypercholesterolemia also plays a pri-
mary role in the progression of diabetes in cats,
eventually preventing the recovery of b-cell function or
viability. Because in the present study the concentrations
of serum triglycerides and of free fatty acids were
not available, it cannot be excluded that these lipid me-
tabolites had a confounding effect on the chance of
remission in our cat population. However, sustained
hypertriglyceridemia and increased free fatty acid con-
centrations did not impair insulin secretion in a recent
study with healthy cats.
8
Based on univariate analysis, diabetic cats treated with
insulin glargine tended to have an increased chance of
remission. Because many cats did not survive to dis-
charge, hence not receiving insulin glargine or porcine
insulin zinc suspension, the multivariate model was
not performed to assess whether the former indepen-
dently predicts remission. A higher probability of
diabetic remission was previously reported in cats treated
with insulin glargine compared with porcine lente
insulin.
7
The duration of diabetic remission varied widely, with
some cats not requiring treatment for few months and
others for many years. More than 10% of cats remained
in remission for more than 1,000 days and 1 cat for
longer than 9 years. Remission lasting more than 1,000
days seems to be uncommon in cats.
3,6
Insulin therapy
was resumed in 13 of the 45 (29%) cats that had experi-
enced remission. Likewise, in 1 report 38% of diabetic
cats in remission had insulin started again to maintain
normoglycemia.
6
Higher body weight was associated with long-lasting
diabetic remission; for a 1 kg increase of body weight at
Table 4. Multivariate analysis of factors associated with
duration of diabetic remission.
Variable
Reference
Range
Duration of Diabetic
Remission
HR 95% CI P-Value
Body weight 0.65 0.420.99 .04
Glucose concentration 90180 mg/dL 1.01 1.001.02 .02
Hematocrit 3345%
Decreased 2.94 0.8610.1 .08
Not decreased
Lipase activity 826 U/L
Increased 1.61 0.426.25 .49
Not increased
CI, condence interval; HR, hazard ratio.
6.0
6.5
7.0
5.0
5.5
3.5
4.0
4.5
B
o
d
y

w
e
i
g
h
t

(
k
g
)
3.0
60 120 180 240 > 240
Duration of remission (days)
Fig 2. Duration of clinical remission and body weight at diagnosis
in diabetic cats followed-up until death. Box and whisker plots are
reported.
1250
1500
750
1000
250
500
G
l
u
c
o
s
e

(
m
g
/
d
L
)
0
60 120 180 240 > 240
Duration of remission (days)
Fig 3. Duration of clinical remission and glucose concentrations at
diagnosis in diabetic cats followed-up until death. Box and whisker
plots are reported.
1319 Remission from Diabetes in Cats
admission remission length increased by almost 35%.
Obese cats are predisposed to insulin resistance, which in
turn poses an excessive demand to b-cells leading to their
exhaustion.
16
In this setting, we assumed that the chance
of remission should be reduced. Unfortunately, it was
not possible to determine whether our cats with higher
body weight had been obese or just were larger cats as
body score was not reported in most medical records.
However, body weight was not signicantly decreased at
the time of remission compared with body weight at 1st
diagnosis (data not shown). Thus, it seems unlikely that
remission occurred due to a reduction of body weight,
which by itself should improve insulin sensitivity and, in
turn, b-cell function or viability. Because cats lose body
weight with untreated diabetes, it cannot be excluded
that the observed association with body weight reects
chronicity of diabetes. Lighter compared with heavier
cats might have experienced subclinical diabetes for a
longer period on presentation. The lighter cats could
have been overweight or obese earlier in life and the in-
sulin resistance they experienced might have reduced
their ability to sustain remission.
Diabetic cats in remission presenting with higher ini-
tial blood glucose concentrations had insulin withdrawn
for a shorter time. Because feline pancreatic islets are ex-
tremely susceptible to the toxic effects of excess glucose,
8
it may be assumed that cats with higher glucose concen-
trations at initial diagnosis had more severe b-cell
damage. The remaining pool of functional b-cells may
thus have been more limited in these cats, hence reducing
the chance of lasting remission. Typically, measurement
of serum fructosamine is indicated to better assess aver-
age blood glucose during the weeks before admission.
17
Different from blood glucose, however, fructosamine
was not associated with longer remission. Thus, further
studies are necessary to conrm the role of blood glucose
concentrations on admission.
There are some limitations of our study that need to be
mentioned. The retrospective nature of the investigation
occasionally resulted in incomplete clinical data records.
However, prospective longitudinal studies spanning over
several years are difcult in veterinary medicine. Hence,
including a relatively large number of cases is easier to
perform in retrospective analysis.
The role of feeding a specic diet, which is important
to improve the control of glycemia in diabetic cats,
18
was
not assessed in the present series because cats were fed
various types or were switched to another in many cases.
Thus, the potential confounding effect of a particular
diet or formulation cannot be ruled out.
Remission applies to cats that achieve normoglycemia
and disappearance of clinical signs of diabetes, without
insulin. According to recent studies performed at our in-
stitution,
5,a
we considered a cat to be in remission after
initial treatment if insulin was not required for at least 4
weeks. Based on the latest American Diabetes Associa-
tion statement, remission in humans with either type 1 or
2 diabetes is dened as attaining normoglycemia in the
absence of active pharmacologic therapy for more than 1
year.
19
Because of the shorter lifespan of cats, this cut-off
does not seem suitable for the feline species.
Footnotes
a
Tschuor F, Furrer D, Kaufmann K, et al. Intravenous arginine
stimulation test in cats with transient and nontransient diabetes
mellitus. J Vet Intern Med 2006;20:725726 (abstract)
b
Caninsulin, Intervet International BV, Boxmeer, the Netherlands
c
Lantus, Sano Aventis (Suisse) SA, Meyrin, Switzerland
d
GraphPad Prism version 4.0, GraphPad Software, San Diego, CA
e
SPSS version 11.0, SPSS Inc, Chicago, IL
Acknowledgments
This study was partially supported by a grant from
Nestle Purina PetCare.
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