effect of dietary carbohydrate, fat, and protein on postprandial glycemia and energy intake in cats

Effect of Dietary Carbohydrate, Fat, and Protein on PostprandialGlycemia and Energy Intake in Cats

H.A. Farrow, J.S. Rand, J.M. Morton, C.A. O’Leary, and G.D. Sunvold

Background: Reducing carbohydrate intake is recommended in diabetic cats and might also be useful in some healthy

cats to decrease diabetes risk.

Objective: To compare postprandial glucose and insulin concentrations and energy intakes between cats fed diets high

in protein, fat, or carbohydrate.

Animals: Twenty-four lean cats with normal glucose tolerance.

Methods: In a prospective randomized study, each of 3 matched groups (n = 8) received a different test diet for

5 weeks. Diets were high in either protein (46% of metabolizable energy [ME]), fat (47% ME), or carbohydrate (47%

ME). Glucose and insulin were measured during glucose tolerance, ad libitum, and meal-feeding tests.

Results: During ad libitum feeding, cats fed the high-carbohydrate diet consumed 25% and 18% more carbohydrate

than cats fed diets high in fat and protein, respectively, and energy intake was highest when the high-fat and high-protein

diets were fed. Regardless of the feeding pattern, cats fed the high-carbohydrate diet had 10–31% higher peak and mean

glucose compared with both other diets; peak glucose in some cats reached 10.4 mmol/L (188 mg/dL) in cats fed 47% ME

carbohydrate and 9.0 mmol/L (162 mg/dL) in cats fed 23% ME.

Conclusions and Clinical Importance: High-carbohydrate diets increase postprandial glycemia in healthy cats compared

with diets high in fat or protein, although energy intake is lower. Avoidance of high- and moderate-carbohydrate diets can

be advantageous in cats at risk of diabetes. Maintenance energy requirements should be fed to prevent weight gain when

switching to lower carbohydrate diets.

Key words: Diet; Feeding pattern; Glucose; Insulin; Type 2 diabetes.

The diet and lifestyle of domestic cats has changedover the last 20–30 years, and they are increas-

ingly kept indoors and are sedentary.1 Cats are nowtypically fed energy-dense food that is moderate tohigh in fat and carbohydrate content, and commonlyfed in excess of their daily energy requirements.2 Insome populations, two of every 3 cats are overweightor obese.3 The overweight condition in cats is associ-ated with increased risk for the development of diabe-tes mellitus, among other diseases.4 As in humans,lifestyle and dietary factors are involved in thedevelopment of diabetes.3,5 Type 2 diabetes in humansand diabetes in cats are very similar diseases clinico-pathologically. In humans, over 50% of patients withtype 2 diabetes are undiagnosed, and prediabetes,defined as impaired glucose tolerance or impaired fast-ing glucose, is 2–4 times more common than diabetes.5

It is unknown if these statistics are true for cats. Thereported prevalence of diabetes in cats has increased,6

and it is likely there are many cats with undiagnosedprediabetes and diabetes.a,b

There is no consensus in veterinary medicine on thebest diet for the prevention of diabetes in cats, with

both moderate-carbohydrate, low-fat, high-protein,high-fiber diets recommended to prevent or manageobesity, and low-carbohydrate, moderate-fat, high-protein diets recommended to reduce postprandialhyperglycaemia.7,8 Minimizing the increase in glucoseconcentration after a meal and the subsequent demandon beta-cells to secrete insulin is a primary goal for themanagement of prediabetic and diabetic humanpatients.9 In humans, it is more important (but alsomore difficult) to normalize postprandial hyperglyce-mia, as compared to fasting glucose concentrations.9

Chronic hyperglycemia increases the demand on thebeta cells to secrete insulin, and chronic hyperinsulin-emia is associated with eventual beta-cell failure andtype 2 diabetes.10 The International Diabetes Federa-tion defines postprandial hyperglycemia in humans as aplasma glucose concentration of greater than7.7 mmol/L (140 mg/dL),11 and glucose toxicity cancause impaired beta-cell function at glucose concentra-tions that are only 1 mmol/L (18 mg/dL) higher thannormal.12–14 Given that the upper cutpoint for normalfasting blood glucose is similar in humans and cats,5,15–17 and that cats have a very prolonged postprandialperiod (≥12 hours),17 postprandial blood glucose con-centrations >7.7 mmol/L (140 mg/dL) might also bedetrimental in cats.18,19 Diets with moderate to highlevels of carbohydrate (6.7–14.5 g carbohydrate/100 kcal; 23–50% metabolizable energy [ME]) result inpeak and mean 24-hour postprandial glucose concen-trations greater than 8 mmol/L (144 mg/dL) in somecats.16–18 Of concern was that a diet with 14.5 g/100 kcal

From the School of Veterinary Science, The University ofQueensland, Brisbane, Qld, Australia (Farrow, Rand, Morton,O’Leary); and the Research and Development, Iams Company,Lewisburg, OH (Sunvold); Morton is presently affiliated withJemora Pty Ltd, Geelong, Vic, Australia.

Corresponding author: Prof. J.S. Rand, School of VeterinaryScience, The University of Queensland, Brisbane, Qld 4072;Australia; e-mail: [email protected].

Submitted September 4, 2012; Revised March 13, 2013;Accepted May 29, 2013.

Copyright © 2013 by the American College of Veterinary InternalMedicine

10.1111/jvim.12139

Abbreviation:

ME metabolizable energy

J Vet Intern Med 2013;27:1121–1135

(51% ME) resulted in peak glucose concentrations ashigh as 10.8 mmol/L (194 mg/dL) in lean cats, and13.4 mmol/L (241 mg/dL) after moderate weight gain(mean body condition score 6.3 out of a 9 point scale),which is considered in the diabetic range for cats.20

Overweight and obese cats have increased mean concen-trations and duration of the postprandial glucose andinsulin response.16,18 Therefore, reduced carbohydratediets might be useful in cats that are at risk of diabetes,especially obese, physically inactive cats, European-origin Burmese cats, diabetic cats in remission, and catswith intrinsically low insulin sensitivity. Low-carbohydrate,moderate-fat, high-protein diets decrease postprandialblood glucose concentrations, insulin requirements, orboth compared with moderate-carbohydrate, low-fatdiets.7,21 However, there is still controversy regardingcarbohydrate content in feline diets, and in mostreported studies comparing diets with differing carbo-hydrate content, other nutritional differences betweenthe diets confounded comparisons.

The aim of this study was to compare postprandialglucose and insulin concentrations and energy intakesbetween healthy cats fed diets high in protein, fat, orcarbohydrate. Importantly, the knowledge gained fromthis study informs the debate about the effect of die-tary carbohydrate content on postprandial glucose andinsulin concentrations, and energy intake. The resultsare relevant to cats at risk of diabetes, especially thosewith insulin resistance, impaired fasting glucose, and/or impaired glucose tolerance.

Materials and Methods

Overview

A randomized controlled trial was performed. Each cat was

allocated to one of 3 groups, matched for sex, body weight, and

mean glucose and insulin concentrations at times 0, 60, and

120 minutes measured during a simplified intravenous glucose

tolerance test,22 performed when cats were consuming the stan-

dard kennel diet, before feeding the “washout” diet (a commer-

cially available premium feline maintenance diet).c The washout

diet was fed to all 24 cats for 5 weeks, and baseline testing was

performed in the 5th week (Fig 1). Each group was then ran-

domly allocated by random draw to one of 3 test diets high in

one of protein, fat or carbohydrate, and fed the diet for 5 weeks.

Each cat (and group) received only one of the test diets. Compo-

sition of the washout and test diets is shown in Table 1. Meta-

bolic tests were performed in the 5th week of consuming the

washout diet (1 week before feeding the test diets), and in the 5th

week of feeding the test diets. During each of the 2 metabolic test

weeks, plasma glucose and insulin concentrations were measured

during a glucose tolerance test, ad libitum feeding test and meal-

feeding test (once daily feeding). Energy intake was measured

during ad libitum feeding tests.

Animals and Dietary Treatments

Twenty-four neutered adult cats (12 male, 12 female) were

used in the trial. All cats were healthy based on physical exami-

nation and routine hematological, serum biochemical, and urine

analyses. Mean body weight was 4.9 kg (range 3.6–6.0 kg). All

cats had an ideal body condition score of 3 as assessed on a scale

of 1 (underweight) to 5 (obese).23 Based on visual assessment, all

cats were estimated to be between 2 and 6 years old, although

accurate ages were unknown. The Animal Experimentation Eth-

ics Committee of the University of Queensland, Australia,

approved the protocol for this study. After the trial, cats were

re-homed.

Each test diet provided approximately 50% of energy from the

test macronutrient, and 25% of energy from each of the other 2

test macronutrients (Table 1). All diets were dry extruded formu-

lations. Both the washout diet and test diets were fed for

5 weeks. Sources of macronutrients and other ingredients were

the same for the washout and test diets. Protein source was

predominantly chicken, and carbohydrate source was corn and

sorghum (Table 1).

Cats were fed the washout and test diets once daily to main-

tain body weight within 10% of their pretrial weight; mean

amounts fed to maintain body weight in individual cats ranged

from 76 to 93 kcal/(kg body weight)0.67 (45–55 kcal/kg body

weight) over the duration of the study. To maintain body weight

at the pretrial weight, food bowls were weighed daily before

each feeding to calculate the amount of food consumed in

24 hours, and cats were weighed weekly, and amount fed

adjusted weekly. Cats were allowed free access to water at all

times.

Metabolic Testing

Metabolic tests were performed in the week before feeding the

test diets (while consuming the washout diet), and again in the

5th week of feeding the test diets. Metabolic testing was per-

formed as follows: day 1, general anesthesia and jugular catheter

placement followed by a meal and removal of food bowls at least

12 hours before the intravenous glucose tolerance test; day 2,

intravenous glucose tolerance test followed by ad libitum feeding;

day 3 ad libitum feeding; day 4, ad libitum feeding test for

12 hours followed by removal of food; day 5, meal fed and unea-

ten food removed 30 minutes later; day 6, 24-hour meal-feeding

test (Fig 1).

A jugular catheterd was placed into 1 jugular vein under gen-

eral anesthesia using a modified Seldinger technique 24 hours

before the glucose tolerance test in each of the 2 test weeks. Dur-

ing catheter placement cats were anesthetised with propofol,e

given as an initial bolus dose of 6–7 mg/kg followed by addi-

tional doses of 5–10 mg as required. The catheter line and port

were held in place via a neck bandage, which was checked daily.

Catheters were flushed twice daily with heparinized saline (20 IU

of heparin/mL in 0.9% saline solution) to maintain patency until

their removal at the end of the meal-feeding test.

Intravenous Glucose Tolerance Test

Blood samples (4 mL) were collected before (�30 and 0 min-

utes) and at 2, 5, 10, 15, 30, 45, 60, 90, 120, and 180 minutes

after 1.0 g/kg body weight glucosef administration.24

Ad Libitum Feeding Test

The ad libitum feeding test was used to mimic the feeding pat-

tern observed in cats when food is freely available. For 36 hours

before the test, cats were allowed unrestricted access to food in

excess of what could be consumed, to facilitate an ad libitum eat-

ing pattern typical of domestic cats characterized by multiple

(10–20) small meals daily.25 At the start of the test, fresh food

was provided in excess of what could be consumed within

12 hours, and blood samples (4 mL) were collected before (�30

1122 Farrow et al

and 0 minutes) and at 1, 2, 3, 4, 6, 8, 10, and 12 hours after

initial placement of food.

Meal-Feeding Test

The meal-feeding test was used to mimic the feeding pattern

commonly observed in overweight cats fed limited energy to lose

weight, and in some ideal weight cats fed at maintenance energy

requirements to prevent weight gain. Typically in these cats the

majority of the food is eaten shortly after feeding. This feeding

pattern also occurred naturally in our cats during the study; cats

were fed once daily at maintenance energy requirements to pre-

vent weight gain. Before the meal-feeding test, food was withheld

for 23.5 hours. During the meal-feeding test, cats ate 90–100%of the 12-hour ad libitum intake as a single meal in 0.5 hour,

after being fed at time 0. This was facilitated by feeding 85 kcal/

kg body weight0.67 (50 kcal/kg body weight) 24 hours before the

test and withdrawing uneaten food 30 minutes after feeding.

Blood samples (4 mL), were collected before (�30 and �5 min-

utes) and at 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, and 24 hours after

feeding.

Sample Handling and Analysis

Blood samples from each of the tests were handled similarly.

Samples were placed into sterile EDTA vacuettes containing the

proteinase inhibitor, Trasylol,g added to the vacuettes at 0.05 mL

per mL of whole blood. After collection, samples were kept on

ice for 10–15 minutes until centrifugation at 1,500 9 g for 8 min-

utes. After separation, plasma samples were split and stored in

500 lL vials at �70°C until assayed for glucose and insulin con-

centration.

Week 0 (W0) W1 - W5 W6 – W10

“Washout” diet Test diet

3 groups (n = 8)

based on IVGTT

Baseline test week

- 5

Final test week

- 10

Test week timetable (days)

1 2 3 4 5 6 7

Morning: Jugular catheter placement

Afternoon: Cats were fed

Evening: food removed at least 12 hours prior to start of the IVGTT

Morning: Glucose tolerance test

Cats fed adlibitum following completion of the test

Cats fed adlibitum.

No testing on this day

Morning: 12 hour ad libitum feeding test

Food removed after completion of test

Cats fed 1meal and allowed 30 minutes to eat.

Cats were then fasted for 23.5 hours

No testing on this day

24 hour meal feeding test

Conclusion of meal feeding test, and removal of jugular catheter

At the conclusion of the final test week, cats were fed a feline maintenance diet and re-homed

Fig 1. Timetable for the study.

High-Carbohydrate Diets and Feline Glycemia 1123

Glucose was measured in plasma using an automated glucose

analyzer.h Insulin was measured using a commercially available

kit,i validated for the detection of feline insulin.

Calculations and Statistical Analysis

For the ad libitum feeding test, 1 cat (cat 17) had an implausi-

bly high insulin concentration recorded at 4 hours (300.6 lU/

mL). As all other values for this cat were within the expected

range, this value was disregarded. Glucose disappearance coeffi-

cients (Kglucose) and glucose half-lives (T1/2) were calculated for

each cat with data from the intravenous glucose tolerance test

using linear regression of the semi-logarithmic plot of glucose

concentration versus time between 15 and 90 minutes after glu-

cose administration.26 Mean 24-hour concentrations for glucose

and insulin (or mean 12-hour concentrations for the ad libitum

feeding test) were calculated for each cat as areas under the curve

(from 0 to 24 hours calculated using the trapezoidal method,27

and expressed as (mg/dL)–hours and (lU/mL)–hours, respec-

tively), divided by 24 or 12 as appropriate. For each test, “base-

line” glucose concentrations were calculated for each cat as the

mean of the �30 and �5 minute values.

Each cat was considered to have exceeded its baseline glucose

concentration if blood glucose concentration at one or more time-

points was greater than the sum of the cat’s individual baseline

concentration and the 90% range of differences. Times to first

exceed baseline and to return to baseline were estimated by linear

interpolation. Cats that did not exceed baseline concentration were

excluded from analyses of times to return to baseline. The 90%

range of differences was calculated using previously reported meth-

odology based on the variance of the 2 baseline samples within

cat28 but with the variance calculated as the residual mean square

from analysis of variance after fitting cat. Concentrations of insulin

at �30 and �5 minutes were log transformed before estimation of

the 90% range of differences.

Energy intakes in the ad libitum feeding tests were calculated

for each cat as the amount of food eaten from initial placement

of food until 12 hours later, multiplied by the energy density of

the diet on an “as fed” basis.29 Energy density on a dry matter

basis was calculated using the modified Atwater factors as pro-

posed by the National Research Council (NRC) and using the

formula proposed by the NRC in 2006.29,30

Baseline, peak, nadir (minimum values after feeding) and

mean 24-hour concentrations or, for the ad libitum feeding test,

Table 1. Nutrient composition and ingredient list of the standard maintenance (“washout”) diet and the 3 testdiets fed to 3 groups of 8 clinically healthy cats, to evaluate the effect of diets high in protein, fat, or carbohydrateon glucose and insulin concentrations, and energy intakes.

Variables

Dietary Nutrient Composition

Caloric Basis (g/100 kcal)

WashoutaHigh

Protein

High

Fat

High

Carbohydrate WashoutaHigh

Protein

High

Fat

High

Carbohydrate

Key values (as-fed basis %)b

Moisture 10.0 6.5 6.6 7.4

Protein 34.0 46.7 31.3 26.5 7.2 12.1 7.1 7.0

Fat 21.0 10.8 23.3 11.2 4.5 2.8 5.3 2.9

Carbohydrate 25.5 27.5 32.3 49.1 5.4 7.1 7.3 12.9

Crude fiber 2.5 1.3 1.3 1.4 0.5 0.3 0.3 0.4

Ash 7.0 7.2 5.2 4.5 1.5 1.9 1.2 1.2

Key values (DM %)

Protein 35.6 49.9 33.6 28.6

Fat 23.3 11.6 24.9 12.1

Carbohydrate 30.0 29.4 34.6 52.9

Approximate energy density (ME)

Total (kcal/kg); NRC 1985b 4,475 3,516 4,205 3,599

Total (kcal/kg); NRC 2006c 4,698 3,851 4,397 3,809

Protein (%)c 29.0 47.0 26.0 26.0

Fat (%)c 46.0 26.0 47.0 27.0

Carbohydrate (%)c 25.0 27.0 27.0 48.0

Main ingredientsd Chicken by-product meal

Corn grits

Corn meal

Ground grain sorghum

Dried beet pulp (sugar removed)

Fish meal

Natural chicken flavor

Dried egg product

Chicken fat (preserved with mixed tocopherols)

DM, dry matter; ME, metabolizable energy.aIams Adult Cat Chicken Dry Food.bMetabolizable energy calculated using the modified Atwater factors, NRC, 1985.cMetabolizable energy calculated using the equation proposed by the NRC, 2006.dIngredients used for diet formulation remained the same between all test diets with the quantity of macronutrients changing to allow

variation in the distribution of calories to facilitate diets that were high in either protein, fat, or carbohydrate.

1124 Farrow et al

mean 12-hour concentrations, glucose disappearance coefficients

(Kglucose) and glucose half-lives (T1/2) and energy intakes were

calculated for each cat and compared between diets using linear

regression with the cat as the unit of analysis. Insulin concentra-

tions were log-transformed before analyses. Distributions of beta-

coefficients were estimated using the nonparametric bootstrap,

with 1,000 replications. Times to peak and times to return to

baseline were compared between diets using Kaplan–Meier analy-

ses with log-rank tests with the cat as the unit of analysis. For

cats that had not returned to baseline by the final timepoint at

which blood was collected, times to return to baseline were right-

censored at that time. Overall P values and P values for pair-wise

comparisons between the 3 diets were calculated. P values were

not adjusted for multiple pair-wise comparisons as all compari-

sons were of a priori interest.

Means for each of glucose and log-transformed insulin dur-

ing the ad libitum and meal-feeding tests were compared

between diets and timepoints using generalized estimating equa-

tions, with cat fitted as the grouping (or panel) variable, and

with diet, timepoint, and the interaction between these fitted as

fixed effects. The cat-timepoint was the unit of analyses where

each measurement timepoint for each cat constituted one cat-

timepoint. Normal error distributions, identity link functions,

exchangeable correlation structures, and the Huber/White/sand-

wich (“robust”) estimator of variance were used. P values for

interactions between diet and timepoint were all <.001, provid-

ing substantial evidence that effects of diet (ie, differences

between concentrations) varied between timepoints, and that

concentrations over time differed by diet. Accordingly, the inter-

action terms were retained in the models and pair-wise compari-

sons then performed: (1) between diets at each timepoint, and

(2) between each timepoint and baseline within each diet. P val-

ues were adjusted for multiple comparisons using the Benja-

mini-Hochberg step-up False Discovery Rate method in

WinPepi (version 11.15).31 All other statistical analyses were

performed using the statistical software package Stata (version

11.1).j Wald P values were used for all linear regression and

generalized estimating equation analyses. Significance was deter-

mined as P values ≤.05.

Results

Effects of Diet on Energy Intake duringad libitum Feeding

After consumption of the “washout” diet for5 weeks, mean (�SD) energy intakes over 12 hours inthe ad libitum feeding test before cats were fed the 3test diets were 108 (�35), 96 (�38), and 134(�41) kcal/kg body weight0.67 for cats subsequentlyfed the high-protein, fat, and carbohydrate diets,respectively.

Energy intake (mean � SD kcal/kg body weight0.67)varied significantly between diets (overall P = .026)during the ad libitum feeding test with higher intakefor the high-protein diet (13 � 39) compared to thehigh-carbohydrate diet (91 � 30; pair-wise P = .012),and a similar trend for higher intake with the high-fatdiet (121 � 36; pair-wise P = .059). There was nosignificant difference in energy intake between thehigh-protein and high-fat diets (pair-wise P = .531;difference between means (high-fat diet minus high-protein diet): �117; 95% CI: �4,726 to 2,413),although the high-fat diet had the highest and thehigh-protein diet the lowest energy density (Table 1).

Results were similar after adjusting (separately) forwashout diet energy intake, for body weight at thattime, and for body weight after the test diets had beenfed for 4 weeks (results not shown). Mean intakes ofenergy supplied by carbohydrate (mean � SD kcal/kgbody weight0.67) were 36 � 11 (high protein), 33 � 10(high fat), and 44 � 14 (high-carbohydrate diets) kcal/kg body weight0.67. Although these did not differ sig-nificantly between diets (overall P = .174; pair-wise Pvalues >.06), numerically, cats fed the high-carbohy-drate diet consumed 25% and 18% more carbohydratethan the cats fed the high-fat and high-protein diets,respectively. When calculated on a kcal/kg basis it was27% and 19% higher.

Effects of Diet on Postprandial Glucose Variablesafter 5 Weeks of Feeding

Glucose variables in the ad libitum and meal-feedingtests were not statistically different between groupsafter consumption of the washout diet for 5 weeks,before the consumption of the test diets (results notshown). After consumption of the test diets for5 weeks, baseline glucose concentrations were higherfor the high-carbohydrate diet compared to both thehigh-protein (P < .001) and high-fat (P = .022) diets inthe ad libitum feeding test; however, cats were notfasted and were eating ad libitum for 36 hours beforethe test (Table 2). In contrast, baseline glucose concen-trations were similar for each diet for the meal-feedingtest where food was withheld for 23.5 hours before thesample collection (overall P = .392).

The lowest glucose concentrations during the ad libi-tum feeding test were higher for the high-carbohydratediet compared to both the high-protein (P = .002) andhigh-fat (P = .043) diets. Lowest glucose concentra-tions were higher for the high-fat diet compared to thehigh-protein diet (P = .024) in the ad libitum feedingtest.

For both ad libitum and meal-feeding tests, con-sumption of the high-carbohydrate diet resulted in10–31% higher mean glucose concentrations and peakglucose concentrations than diets high in either proteinor fat (Figs 2, 3; Table 2). In general, cats fed thehigh-carbohydrate diet had the highest peak and meanglucose concentrations, and those fed the high-proteindiet had the lowest in both feeding tests (P for overalleffect of diet <.001 to .012); pair-wise P (high carbohy-drate compared to high protein <.001 to .004)(Tables 2, 3). The greatest difference in glucose con-centrations between cats fed the different diets was forpeak glucose concentration in cats meal-fed the high-carbohydrate diet (8 mmol/L; 151 mg/dL); which was31% higher than for the high-protein diet (6 mmol/L;115 mg/dL) (pair-wise P < .001). Similarly, the greatestdifference in mean glucose concentration between catsfed the different diets was for cats meal-fed the high-carbohydrate diet (7 mmol/L; 119 mg/dL), which was25% higher than for the high-protein diet (5 mmol/L;95 mg/dL) (P = .001). In summary, although cats fedthe high-protein and high-fat diets ingested approxi-


Table

2.

Arithmetic

mean�

SEM

(SD;range)

forplasm

aglucose

variablesandglucose

toinsulinratiosduringanintravenousglucose

tolerance

test,a12-hour

adlibitum

feedingtest

anda24-hourmealfeedingtest

in3groupsofcats

(n=8in

each

group)after

beingfedadiethighin

protein,fat,orcarbohydrate

for

4weeks,andmedian(range)

oftimes

topeakandto

return

tobaseline.

Meanswithdifferentsuperscripts

differ

significantlyatthe.05level.

Variable

HighProtein

HighFat

HighCarbohydrate

Overall

PValue

Intravenousglucose

tolerance

test

Baselineglucose

concentration(m

g/dL)

97�

4(12;4–119)

98�

5(14;86–127)

105�

7(19;83–138)

.636

Peakglucose

concentration(m

g/dL)

872�

52(148;712–1,119)

896�

16(44;832–958)

885�

19(54;820–976)

.835

Nadirglucose

concentration(m

g/dL)

78�

2(5;71–85)

94�

18(51;2–189)

97�

11(30;73–169)

.155

Meanglucose

concentration(m

g/dL)

276�

19(53;206–340)

304�

17(49;238–397)

292�

12(34;253–343)

.534

Kglucose(%

/min)

1.3

�0.2

(0.5;0.6–2.0)

1.4

�0.1

(0.3;1.0–1.8)

1.3

�0.1

(0.2;1.0–1.5)

.713

Glucose

T1/2(m

in)

62�

9(27;35–119)

53�

4(11:39–70)

55�

3(7;46–67)

.618

Adlibitum

feedingtest

Baselineglucose

concentration(m

g/dL)

92�

2a(4;85–97)

96�

3a(8;87–110)

107�

4b(11;97–132)

<.001

Baselineglucose

concentration(m

mol/L)

5.1

�0.1

a(0.2;4.7–5.6)

5.3

�0.2

a(0.4;4.8–6.1)

5.9

�0.2

a(0.6;5.4–7.3)

Peakglucose

concentration(m

g/dL)

99�

3a(9;91–114)

104�

3a(10;90–117)

128�

9b(26;110–191)

.012

Peakglucose

concentration(m

mol/L)

5.5

�0.2

a(0.5;5.1–6.3)

5.8

�0.2

a(0.6;5.0–6.5)

7.1

�0.5

b(1.4;6.1–10.6)

Nadirglucose

concentration(m

g/dL)

83�

2a(7;74–95)

90�

2b(5;82–97)

102�

6c(13;91–132)

.003

Nadirglucose

concentration(m

mol/L)

4.6

�0.1

a(0.4;4.1–5.3)

5.0

�0.1

b(0.3;4.6–5.4)

5.7

�0.3

c(0.7;5.1–7.3)

Meanglucose

concentration(m

g/dL)

91�

2a(7;85–101)

97�

3a(7;87–110)

115�

8b(23;100–170)

.008

Meanglucose

concentration(m

mol/L)

5.1

�0.1

a(0.4;4.7–5.6)

5.4

�0.2

a(0.4;4.8–6.1)

6.4

�0.4

b(1.3;5.6–9.4)

Glucose

toinsulinratio(m

g/dL)/(lU/m

L)

4�

0.3

(1;2–6)

4�

0.2

(0.7;3–5)

5�

0.5

(2;3–8)

.264

Mealfeedingtest

Baselineglucose

concentration(m

g/dL)

82�

2(5;74–91)

82�

2(5;73–89)

90�

7(15;74–120)

.392

Baselineglucose

concentration(m

mol/L)

4.6

�0.1

(0.3;4.1–5.1)

4.6

�0.1

(0.3;4.1–4

.9)

5.0

�0.4

(0.8;4.1–6.7)

Peakglucose

concentration(m

g/dL)

115�

8a(21;93–163)

122�

5a(14;96–141)

151�

7b(19;128–188)

.001

Peakglucose

concentration(m

mol/L)

6.4

�0.4

a(1.2;5.2–9.0)

6.8

�0.3

a(0.8;5.3–7.8)

8.4

�0.4

b(1.1;7.1–10.4)

Tim

eto

peakglucose

concentration(h)

6(3–24)

6(6–12)

6(3–15)

.952

Meanglucose

concentration(m

g/dL)

95�

3a(10;84–111)

98�

1a(4;89–101)

119�

6b(16;104–155)

<.001

Meanglucose

concentration(m

mol/L)

5.3

�0.2

a(0.6;4.7–6.2)

5.4

�0.1

a(0.2;4.9–5.6)

6.6

�0.3

b(0.9;5.8–8.6)

Glucose

toinsulinratio(m

g/dL)/(lU/m

L)

7�

0.4

(1;6–10)

6�

0.4

(1;5–8)

8�

1(3;5–12)

.147

Tim

eforglucose

toreturn

tobaseline(h)

23(14to

>24)

3of8cats

hadnotreturned

tobaselineby24hours

20(12to

>24)

1of8cats

hadnotreturned

tobaselineby24hours

24(11to

>24)

4of8cats

hadnotreturned

tobaselineby24hours

.376

1126 Farrow et al

mately 43% and 31% more energy, respectively, thanthose fed the high-carbohydrate diet, their baseline,highest, lowest, and mean glucose concentrations inthe ad libitum feeding test were significantly lower thanfor cats fed the high-carbohydrate diet.

Cats meal-fed the high-fat diet had significantlylower glucose peak and mean concentrations than

those eating the high-carbohydrate diet (P < .001), butpeak and mean concentrations were not significantlydifferent between cats eating the high protein andhigh-fat diets (Figs 2, 3; Tables 2, 3). In cats fed thehigh-fat diet, the greatest difference in peak glucoseconcentration was in the meal-feeding test (mean ofpeak values 7 mmol/L; 122 mg/dL), which was 20%

Time from start of sampling (hours)0 5 10 15 20 25

Glu

cose

con

cent

ratio

n (m

mol

/L)

0

4

5

6

7

8

9

10

Glucose concentration (m

g/dL)

0

80

90

100

110

120

130

140High Protein High Fat High Carbohydrate

a

a a

a

a

aaa,b

aaa

a

a,b

a,b

b

b

bb

bbb

Fig 3. Plasma glucose concentrations (mean � SEM) during a 24-hour meal-feeding test in 3 groups of cats (n = 8 in each group) after

being fed a diet high in protein, fat, or carbohydrate for 4 weeks. Food was withheld for 23.5 hours before testing. Within a timepoint,

means with different letters (a or b) differed at the .05 level.

Time from start of sampling (hours)0 2 4 6 8 10 12

Glu

cose

con

cent

ratio

n (m

mol

/L)

0

4

5

6

7

8

9

10

Glucose concentration (m

g/dL)

0

80

90

100

110

120

130

140

High Protein High Fat High Carbohydrate

aa a a a a aa

a aaaa,b a,b a,bb

b b bb b

bb b

Fig 2. Plasma glucose concentrations (mean � SEM) during a 12-hour ad libitum feeding test in 3 groups of cats (n = 8 in each group),

after being fed a diet high in protein, fat, or carbohydrate for 4 weeks. Cats were fed ad libitum for the 36 hours preceding and during

the test. Within a timepoint, means with different letters (a or b) differed at the .05 level. NB: Values for variables derived from graphs

may appear different from those in tables. Variables in tables are calculated from individual cat data whereas figures show mean data

for each timepoint.


lower than for the high-carbohydrate diet (8 mmol/L;151 mg/dL) (P < .001, Table 2).

A number of cats in all 3 test groups did not returnto baseline glucose concentrations after 24 hours in themeal-feeding test (3/8 cats fed the high-protein diet,1/8 cats fed the high-fat diet, and 4/8 cats fed thehigh-carbohydrate diet). The median times to peakglucose concentration were 6 hours in the meal-fed

cats for all diets (P = .952), and median times toreturn to baseline were 23, 20, and 24 hours (P = .376)for the high protein, high fat, and high-carbohydratediets, respectively (Table 2).

After consumption of the test diets for 5 weeks,there was no significant difference for any variablebetween diets during the intravenous glucose tolerancetest (Table 2).

Table 3. Means � SD,a differences between means/ratios of means and associated confidence intervals and P val-ues for mean and peak glucose and insulin concentrations, and glucose to insulin ratio.

Diet

Difference/

Ratiob (95% CI) P ValueHigh Protein High Fat

High

Carbohydrate

Ad libitum-feeding test

Peak glucose (mg/dL) (mmol/L)

99 � 9 (5.5 � 0.5) 104 � 10 (5.8 � 0.6) 5.13 (�4.03–14.29) .272

99 � 9 128 � 26 (7.1 � 1.4) 28.72 (9.37–48.06) .004

104 � 10 128 � 26 23.59 (3.67–43.50) .020

Mean glucose (mg/dL) (mmol/L)

91 � 7 (5.1 � 0.4) 97 � 7 (5.4 � 0.4) 5.65 (�1.25–12.54) .108

91 � 7 115 � 23 (6.4 � 1.3) 23.92 (7.55–40.29) .004

97 � 7 115 � 23 18.27 (1.46–35.09) .033

Peak insulin (µU/mL)

26.1 � 5.2 29.4 � 6.2 1.13 (0.93–1.36) .228

26.1 � 5.2 30.9 � 9.6 1.18 (0.93–1.51) .170

29.4 � 6.2 30.9 � 9.6 1.05 (0.82–1.35) .684

Mean insulin (µU/mL)

21.4 � 14.4 25.0 � 17.0 1.17 (0.96–1.43) .125

21.4 � 14.4 25.0 � 12.6 1.17 (0.88–1.56) .272

25.0 � 17.0 25.0 � 12.6 1.00 (0.77–1.31) .991

Glucose to insulin ratio (mg/dL/µU/mL)

4.33 3.91 �0.42 (�1.15–0.31) .258

4.33 4.70 0.37 (�0.80–1.54) .537

3.91 4.70 0.79 (�0.31–1.89) .160

Meal feeding test

Peak glucose (mg/dL) (mmol/L)

115 � 21 (6.4 � 1.2) 122 � 14 (6.8 � 0.8) 6.47 (�9.98–22.91) .441

115 � 21 151 � 19 (8.4 � 1.1) 35.74 (17.07–54.40) <.001122 � 14 151 � 19 29.27 (13.46–45.08) <.001

Mean glucose (mg/dL) (mmol/L)

95 � 10 (5.3 � 0.6) 98 � 4 (5.4 � 0.2) 3.13 (�3.84–10.09) .379

95 � 10 119 � 16 (6.6 � 0.9) 23.94 (11.37–36.51) <.00198 � 4 119 � 16 20.82 (9.39–32.24) <.001

Peak insulin (µU/mL)

22.0 � 5.0 21.9 � 4.7 1.00 (0.83–1.20) .962

22.0 � 5.0 24.3 � 9.8 1.10 (0.84–1.44) .475

21.9 � 4.7 24.3 � 9.8 1.11 (0.85–1.44) .449

Mean insulin (µU/mL)

13.9 � 2.3 16.0 � 2.3 1.15 (0.99–1.33) .073

13.9 � 2.3 15.6 � 4.7 1.12 (0.89–1.41) .340

16.0 � 2.3 15.6 � 4.7 0.97 (0.77–1.23) .829

Glucose to insulin ratio (mg/dL/µU/mL)

6.87 6.20 �0.67 (�1.70–0.36) .204

6.87 7.97 1.10 (�0.93–3.13) .288

6.20 7.97 1.77 (�0.22–3.76) .082

aArithmetic means are reported for glucose variables and glucose to insulin ratio; geometric means are reported for insulin variables

because these required log-transformation before analyses and the resulting effect estimates (Euler’s number raised to the power of the

regression coefficients) can be interpreted as ratios of geometric means.bDifference between arithmetic means for glucose variables and glucose to insulin ratio; ratio of geometric means for insulin

variables.

1128 Farrow et al

Table

4.

Arithmetic

mean�

SEM

(SD;range)

forplasm

ainsulinvariablesduringanintravenousglucose

tolerance

test,a12-houradlibitum

feedingtest

anda

24-hourmeal-feedingtest

in3groupsofcats

(n=8in

each

group)after

beingfedadiethighin

protein,fat,orcarbohydrate

for4weeks,andmedian(range)

of

times

topeakandto

return

tobaseline.

Meanswithdifferentsuperscripts

differ

significantlyatthe.05level.

Variable

HighProtein

HighFat

HighCarbohydrate

Overall

PValue

Intravenousglucose

tolerance

test

Baselineinsulinconcentration(µU/m

L)

10.3

�0.9

(2.7;7.1–13.6)

10.6

�0.5

(1.4;8.4–1

2.1)

11.3

�1.1

(3.0;8.3–16.0)

.795

Peakinsulinconcentration(µU/m

L)

28.9

�2.0

(5.7;20.5–3

6.4)

37.6

�7.7

(22.2;23.6–91.1)

36.8

�4.1

(11.6;18.8–52.4)

.259

Nadirinsulinconcentration(µU/m

L)

7.9

�1.4

(4.0;1.6–15.6)

7.2

�0.9

(2.6;3.3–1

2.6)

7.7

�0.8

(2.2;3.4–11.0)

.893

Meaninsulinconcentration(µU/m

L)

19.8

�1.4

(3.9;14.0–2

4.9)

22.9

�2.2

(6.3;15.6–37.1)

23.5

�2.5

(7;11.4–30.4)

.387

Adlibitum

feedingtest


L)

20.2

�1.6

a(4.5;14.1–26.6)

25.5

�1.7

b(4.8;18.3–33.2)

27.0

�3.8

a,b(10.9;14.2–4

6.1)

.056


L)

26.5

�1.8

(5.2;20.5–3

5.9)

30.0

�2.2

(6.2;22.0–38.2)

32.1

�3.3

(9.6;17.2–48.8)

.294

Nadirinsulinconcentration(µU/m

L)

17.4

�1.4

(3.9;12.2–2

1.9)

20.8

�1.9

(5.5;11.7–28.0)

20.8

�3.4

(9.6;9.4–42.0)

.424


L)

21.9

�1.8

(5.0;15.5–5

3.8)

25.4

�1.6

(4.7;18.8–31.7)

26.5

�3.5

(9.8;14.0–46.2)

.275

Mealfeedingtest


L)

11.0

�1.1

(3.2;7.8–16.6)

10.6

�1.0

(2.9;6.1–1

4.2)

9.2

�1.2

(3.3;6.2–14.8)

.397


L)

22.5

�1.6

(4.6;14.4–2

7.2)

22.2

�1.3

(3.6;17.0–26.9)

25.5

�2.9

(8.1;12.6–36.4)

.734

Tim

eto

peakinsulinconcentration(h)

5(1–8)

6(2–18)

6(4–12)

.161


L)

14.1

�0.8

(2.3;9.6–16.8)

16.1

�0.8

(2.3;12.5–19.5)

16.2

�1.7

(4.7;8.8–22.5)

.186

Tim

eforinsulinto

return

tobaseline(h)

13(3

to>24)

1of7cats

hadnotreturned

tobaselineby24hours

17(3

to>24)

2of8cats

hadnotreturned

tobaselineby24hours

21(9

to>24)

2of8cats

hadnotreturned

tobaselineby24hours

.436


Effects of Diet on Postprandial Insulin Variablesafter 5 Weeks of Feeding

Insulin variables during the ad libitum and meal-feeding tests were similar between groups after con-sumption of the “washout” diet for 5 weeks, beforeconsumption of the test diets (results not shown).

After consumption of the test diets for 5 weeks,there was some evidence that baseline insulin concen-trations were higher for the high-fat diet compared tothe high-protein diet (P for overall effect ofdiet = .056; pair-wise P [high fat compared to highprotein] = .022) in the ad libitum feeding test; cats werefed ad libitum for 36 hours before sampling (Table 4).

Time from start of sampling (hours)0 2 4 6 8 10 12

08

10

12

14

16

18

20

22

24

26

28

30

32


Insu

lin c

once

ntra

tion

(µU

/mL)

Fig 4. Plasma insulin concentrations (mean � SEM) during a 12-hour ad libitum feeding test in 3 groups of cats (n = 8 in each group)

after being fed a diet high in protein, fat, or carbohydrate for 4 weeks. Cats were fed ad libitum for the 36 hours preceding and during

the test. Within each timepoint, no means differed at the .05 level.

Time from start of sampling (hours)0 5 10 15 20 25

08

10

12

14

16

18

20

22

24

26

28

30

32


Insu

lin c

once

ntra

tion

(µU

/mL)

Fig 5. Plasma insulin concentrations (mean � SEM) during a 24-hour meal-feeding test in 3 groups of cats (n = 8 in each group) after

being fed a diet high in protein, fat, or carbohydrate for 4 weeks. Food was withheld for 23.5 hours before testing. Within each time-

point, no means differed at the .05 level.

1130 Farrow et al

The greatest numerical difference in baseline insulinconcentration was for cats fed ad libitium the high-carbohydrate diet; the arithmetic mean was 27.0lU/mL, which was 34% higher than for the high-pro-tein diet (20.2 lU/mL; P for pair-wise comparisonafter log transformation of data = .117) (Table 4).

For both ad libitum and meal-feeding tests, therewas a consistent trend for peak insulin concentrationto be highest following consumption of the high-carbohydrate diet but these differences were not statis-tically significant. The high-fat diet produced insulinconcentrations that were more similar to the high-carbohydrate diet than high-protein diet (Table 4,Fig 4, 5).

The greatest numerical difference in mean insulinconcentration for cats fed ad libitum was for thehigh-carbohydrate diet (arithmetic mean = 26.5lU/mL; Table 4), which was 21% higher than for thehigh-protein diet (21.9 lU/mL; P for pair-wise com-parison after log transformation of data = .272)(Table 4).

Median times to peak insulin concentration were 5,6, and 6 hours (P = .161) in the meal-fed cats for thehigh-protein, high-fat, and high-carbohydrate dietsrespectively. The highest insulin concentrations were26.5, 30.0, and 32.1 lU/mL in the cats fed ad libitum,and 22.5, 22.2, and 25.5 lU/mL in meal-fed cats (over-all P values .294 and .734) for the high-protein, high-fat, and high-carbohydrate diets, respectively(Table 4). Time to return to baseline insulin concentra-tion in the meal-feeding test was 13, 17, and 21 hours(P = .436) for the high-protein, high-fat, and high-carbohydrate diets, respectively (Table 4).

Effects of Diet on Postprandial Glucose to InsulinRatios after 5 Weeks of Feeding

Glucose to insulin ratios in the postprandial per-iod were highest for the high-carbohydrate diet andlowest for the high-fat diet, with the pair-wise differ-ence between these diets showing a trend towardsignificance for the meal-feeding test (P = .082;Table 3).

Discussion

Our study showed that in healthy lean cats, con-sumption of a diet with approximately 50% of energyfrom carbohydrate (12.9 g/100 kcal) resulted in higherpeak and mean blood glucose concentrations for4–18 hours after eating, compared with consumptionof a high protein or a fat diet containing approximately25% of energy from carbohydrate (4.5–5.4 g/100 kcal).Cats consuming the high-protein diet consumed moreenergy than cats consuming the high-carbohydrate diet.However, the overall effect was that cats fed the high-carbohydrate diet consumed 25% more carbohydratethan cats fed the high-fat diet, and had 19–25% highermean and 23% higher peak glucose concentrations.Similarly, cats fed the high-carbohydrate diet consumedan 18% higher carbohydrate load than cats fed the

high-protein diet, and had 25–30% higher mean and30% higher peak glucose concentrations. This findinghas important implications for cats predisposed todiabetes, for example obese and European-originBurmese cats, and cats with insulin resistance. It is alsolikely important for cats already exhibiting some degreeof beta cell failure resulting in impaired glucosetolerance—some obese cats and the majority of diabeticcats in remission.18,32 Decreasing the glucose load froma meal has been shown to be important for achievingremission in diabetic cats.21 Although our study com-pared a high-carbohydrate diet with a moderate-carbo-hydrate diet, further decreasing carbohydrate contentto ≤12% ME has been shown to increase remissionrates in diabetic cats. In fact, the highest remissionrates (>80%) have only been reported using diets withapproximately ≤6% of energy from carbohydrate.33,34

The results of our study highlight the likely mechanismfor these observations—decreasing dietary carbohydrateload reduces the postprandial blood glucose elevation,which in cats is prolonged.17,18 In our study, blood glu-cose remained above baseline for 11 to >24 hours incats fed the high-carbohydrate diet. For all 3 dietstested, some cats had peak blood glucose values morethan 1 mmo/L (18 mg/dL) above the upper referencerange for cats (<6–6.5 mmol/L; 108–117 mg/dL).35 Ofconcern was in some cats fed the high-carbohydratediet, peak glucose concentration (10.4 mmol/L;150 mg/dL) was in the range reported for diabeticcats.20 Even in some cats consuming the high-proteindiet, peak glucose concentration was as high as9.0 mmol/L (162 mg/dL). This finding might explainwhy, in diabetic cats, a diet with 3.5 g/100 kcal ME(12% ME) from carbohydrate resulted in higher remis-sion rates than one with 7.6 g/100 kcal ME (24%ME).21 Although the diets in the latter study differed iningredient sources, fiber content, and micronutrients,which could have accounted for some of the differencesobserved, the carbohydrate content differed markedlybetween them, and 2 mechanisms likely explain thefindings. Firstly, the higher postprandial glucose con-centrations from the higher carbohydrate load make itless likely that a cat with very marginal beta cell func-tion can secrete sufficient insulin to maintain euglyce-mia. In addition, the ongoing effect of glucose toxicitysuppresses insulin secretion and prevents recovery ofsufficient beta cell function to maintain euglycemia.The magnitude of the increase in postprandial glucoseconcentrations would likely be even greater hadoverweight and obese cats been studied.16,18

The increase in blood glucose concentrations after acarbohydrate load is accentuated in cats compared todogs and humans.5,19,36 The relative carbohydrateintolerance of cats might be because of a number ofunique features associated with glucose metabolism inthis species, and could also contribute to theirextended postprandial period of 8–15 hours comparedto 2–3 hours for humans5 and 3–6 hours for dogs.37

The gluconeogenic pathway is almost always perma-nently “switched on.”38 Cats have markedly reducedor absent glucokinase concentrations,39 and rely on


low-capacity hexokinase to clear a glucose load.40

Further, delayed gastric emptying,k reduced smallintestinal disaccharidase activity,41 and reduced anddelayed insulin secretion compared with dogs36 aresome of the factors that result in cats having reducedcapacity to decrease glucose concentrations after theingestion of a high-carbohydrate load.19,36

The lower blood glucose concentrations in our catsfed the lower carbohydrate diets is consistent with pre-vious findings,16,40 however, others have not reporteddifferences, largely because of the methodologyused,42–45 or the difference in carbohydrate contentwas not as great.46 It was not surprising that we foundno differences in glucose tolerance test results betweenthe diets, because the glucose tolerance test is per-formed after a 24-hour fast, and the glucose load isthe same for all cats. For there to be differences, itwould imply that there was a physiological adaptionto a given dietary carbohydrate load that was notmodifiable in the short term for a different carbohy-drate load. Therefore, the glucose tolerance test is nota sensitive test for determining the daily impact ofdiets on glucose and insulin concentrations; its use isto assess glucose tolerance status. Similarly, time 0glucose concentrations were not different between dietsfor the meal-feeding test because cats had been fastedfor 23.5 hours. In contrast, for the ad libitum feedingtest, cats had access to food continuously before time0, and hence their time 0 glucose concentrationsreflected the effect of diet on postprandial glucose con-centrations, which were significantly different betweendiets.

There were also 2 trends worth noting: firstly, post-prandial insulin concentrations were consistentlyhigher after the high-carbohydrate diet was consumedcompared to the high-protein diet, but were similar tothe high-fat diet. The small group size (n = 8), higherCV for the insulin assay compared to glucose assay,and the variability in the actual amount of foodconsumed by each cat likely contributed to the vari-ability in insulin results and lack of statistical signifi-cance. Secondly, glucose to insulin ratio was highestfor the high-carbohydrate diet and lowest for the high-fat diet. The finding of a trend to the highest glucose toinsulin ratio for the high-carbohydrate diet mightreflect the higher glucose concentrations, secondary tothe high carbohydrate load coupled with reduced clear-ance of blood glucose in cats.19,36 An additional con-tributing factor was that insulin concentrations in catsfed the high-fat diet were similarly high to those fed thehigh-carbohydrate diet. This finding might be relatedto stimulation of incretin secretion by free fatty acids inthe high-fat diet, which increases insulin secretion.47,48

In our study, dietary protein did not appear to be asubstantial driver of postprandial insulin concentra-tions in cats compared to dietary carbohydrate. This isdespite amino acids being secretagogues for insulin indogs, cats and humans.49,50 However, this finding mayhave been because of the postprandial amino acid con-centrations being insufficient to fully stimulate insulinsecretion.51 Therefore, to reduce the postprandial

increase in glucose and the subsequent demand forpostprandial insulin secretion, restricting carbohydratecontent appears most effective in cats. Our results areconsistent with results from studies in humans anddogs, which indicate that carbohydrates are the princi-pal nutrients involved in determining the magnitude ofthe postprandial changes in plasma glucose andinsulin.52,53 Based on the collective effects in our studyof diet on peak and mean glucose and insulin concen-trations, substitution of protein for carbohydratewould be expected to lead to lower postprandial glu-cose and insulin concentrations compared to substitu-tion with fat.

Obesity is a recognized risk factor for developmentof diabetes,4,54 and in our study, cats fed the high-pro-tein and high-fat diets consumed more energy than thehigh-carbohydrate diet. Cats consuming the high-protein diet consumed 9% more energy than catseating the high-fat diet, but the difference did notreach statistical significance. Although previous studieshave reported high-fat diets fed ad libitum are associ-ated with obesity in cats,44,54,55 the energy consump-tion of the high-protein diet was less expected.However, in a recent study, when cats were fed dietsof the same energy density and similar fat content,those eating a low-carbohydrate, moderate-fat, high-protein diet gained more weight than those on a highcarbohydrate, moderate-fat, low-protein diet, so it wasunknown which macronutrient had the greatest effecton weight gain.16 Weight gain was reported to becaused by the higher energy efficiency of the low-carbohydrate, moderate-fat, high-protein diet.16 Thefinding in our study that cats consuming the high-carbohydrate diet had the lowest energy intake wasexpected because cats are reported to limit their totalenergy intake when consuming a high-carbohydratediet.40 Cats have a ceiling for carbohydrate intake,which limits ingestion when consuming high carbohy-drate foods and constrains them to deficits in proteinand fat intake, relative to their targets for thesemacronutrients.40 The authors suggested this “carbo-hydrate ceiling” can reflect the cats’ adaption to acarnivorous diet. In the same study, cats overshot pro-tein intake relative to their protein target, presumablyto gain energy (a limiting resource).40 The similarenergy intakes observed in our study with the highprotein and high-fat diets, and lower intake with thehigh-carbohydrate diet, might have simply reflectedthat cats fed the high-protein and high-fat diets wereeating to achieve a similar perceived required energyintake, and cats fed the high-carbohydrate diet hadlower energy intake because of the need to limit car-bohydrate intake to a ceiling, which was reported tobe 75 kcal/cat/day (approximately 30% of cats’ main-tenance energy requirements) for cats fed a high-car-bohydrate diet for a week. Our cats consumed onaverage 129 kcal/cat/day (approximately 53% of thestudy cats’ maintenance energy requirements) of car-bohydrate, after being fed the high-carbohydrate dietfor 5 weeks, and we have previously reported that catsfed a high-carbohydrate diet for longer periods have

1132 Farrow et al

even higher levels of carbohydrate intake. For exam-ple, cats fed for 4 weeks at maintenance energyrequirements and 8 weeks ad libitum, consumed150 kcal/cat/day of carbohydrate (approximately 88%of the study cats’ maintenance energy requirements),double the carbohydrate ceiling reported in cats fed ahigh-carbohydrate diet for 1 week. This suggests thatover time, the carbohydrate ceiling is higher if cats aremore adapted to the diet.

Our finding of the highest energy consumption withthe high-protein diet and lowest with the high-carbo-hydrate diet might explain why there is no clear evi-dence from epidemiological studies of an effect ofdietary composition on the predisposition to diabetes.Higher consumption of the high-protein and high-fatdiets leading long term to obesity might counter thebeneficial effect of lower glucose concentrations.Indeed, findings from a recent study in cats suggestedthat feeding a diet with 50% of energy from carbohy-drate produced similar adverse effects on mean post-prandial blood glucose and insulin concentrations asshort-term moderate weight gain, although other die-tary differences might have confounded results.16 Oneepidemiological study has reported a dietary effect onrisk of diabetes. In a study among feline patients inthe United Kingdom, consumption of a mix of wetand dry foods was associated with a lower risk for dia-betes, compared to only dry diets (typically high car-bohydrate, moderate fat, and protein), or only wetdiets (typically lower in carbohydrate and higher in fatand protein).56 In that study, cats fed wet diets were 3times more likely to develop diabetes than cats fedmixed diets; cats fed dry diets had 2 times the risk,suggesting the adverse effect of obesity was greaterthan the adverse effect of increased postprandial glyce-mia on risk of diabetes. Although wet foods have onaverage lower carbohydrate content than dry foods,the sauces may contain simple sugars, which would beexpected to exacerbate postprandial glycemia. Well-designed studies are urgently required to better under-stand dietary risk factors for feline diabetes. In ourstudy, cats were fed ad libitum for only 48 hours, andintake measured in the last 12 hours. The effects offat, protein and carbohydrate on energy intake andrisk of diabetes need to be evaluated over a longertime to determine if this finding is true over longerperiods.

An important factor that differentiates our studyfrom others is that all diets used contained the sameingredients and did not differ in carbohydrate sourcebecause this may cause some variation in blood glu-cose concentration.18 The carbohydrate source usedin our study (corn/sorghum) produces a lower glyce-mic response in cats than rice, which is commonlyused as a starch source in feline diets.18 Fiber sourceswere also the same between diets (mostly soluble fiberfrom beet pulp). Fiber content was similar betweenall test diets (0.3–0.5 g/100 kcal), and comparable inamount to a low-fiber, low-carbohydrate diet (0.1 g/100 kcal) associated with increased remission rates indiabetic cats, when compared to a high fiber, moder-

ate-carbohydrate diet (3.1 g/100 kcal).21 There arealmost no data in the literature on the effect of fiberon postprandial glucose concentrations in cats. Onestudy reported that a high-fiber diet (3.9 g/100 kcal)promoted better glycemic control in diabetic catsthan a diet lower in fiber (0.5 g/100 kcal).57 However,results were confounded by differences in carbohy-drate content between diets, as the low-fiber diet hadhigher carbohydrate content (38% DM) than thehigh-fiber diet (27% DM). In our study, the carbohy-drate load may not be responsible for the entirety ofthe differences seen between the diets used in ourstudy, and other unidentified effects of protein andfat may have influenced the results, including incretineffects and effects of fat and carbohydrate on insulinsensitivity. However, it is not possible to test just 1effect in isolation from the others, because changing1 macronutrient inevitably changes others—loweringcarbohydrate content must result in increases ineither fat, protein, or both. It is clear that furtherstudies are needed in this area of feline nutrition togain better understanding of the effects of dietarymacronutrients on energy intake and postprandialglucose concentrations, and the subsequent risk forobesity and diabetes.

In conclusion, our study shows that a diet withapproximately 50% of energy (12.8 g/100 kcal) fromcarbohydrate results in significantly higher postpran-dial blood glucose concentrations for a median of24 hours after eating compared to diets with approxi-mately 25% of energy from carbohydrate (7.1–7.3g/100 kcal) and 50% from either fat or protein. How-ever, even diets with 25% of energy from carbohydrateresult in peak blood glucose concentrations as high as9 mmol/L (162 mg/dL) after eating in lean cats withnormal glucose tolerance. Given the frequency ofimpaired glucose tolerance in obese cats, diets withcarbohydrate content <25% ME are recommended tominimize postprandial glucose and insulin response,and to avoid potential glucose toxic damage to betacells. However, the high-protein diet was associatedwith the highest energy intake, and so cats at risk ofdiabetes should be fed at maintenance energy require-ments to avoid obesity. Further research is required todetermine the optimum level of dietary carbohydrate,fat, and protein for cats.

Footnotes

a Reeve-Johnson MK, Rand JS, Anderson S, et al. Determina-

tion of reference values for casual blood glucose concentration

in clinically healthy, aged cats measured with a portable glucose

meter from an ear or paw sample. J Vet Intern Med

2012;26:755 (abstract)b Gottlieb S, Rand JS, Marshall RD. Diabetic cats in remission

have mildly impaired glucose tolerance. J Vet Intern Med

2011;25:682–683 (abstract)c Iams Adult Cat Chicken Dry Food; Iams Company, Lewisburg,

OH


d 18 gage 9 8 cm polyurethane jugular catheter; Cook Veterinary

Products, Bloomington, INe Diprivan 10 mg/mL; AstraZeneca S.p.A., Caponago, Italyf Glucose Pfizer, West Ryde, NSW, Australiag Aprotinin, Trasylol, Kallikrein Inactivator, 10,000 U/mL;

Bayer, Pymble, NSW, Australiah Olympus 400 Biochemistry Analyzer; Beckman Coulter Austra-

lia Pty Ltd, Lane Cove, NSW, Australiai Phadeseph Insulin RIA; Pharmacia and Upjohn Diagnostics

AB, Uppsala, Swedenj StataCorp, College Station, TXk Coradini M, Rand JS, Morton JM, Filippich LJ. Delayed gas-

tric emptying may contribute to prolonged postprandial hyper-

glycemia in meal-fed cats. J Vet Intern Med 2006;20:726–727(abstract)

Acknowledgments

The authors thank the Iams Company, Procter &Gamble, Lewisburg, OH 45338, USA for contributingfunding towards the study and Lyn Knott for helpwith sample analysis, Delisa Appleton and LindaFleeman for technical assistance and advice and Cait-lin McGuckin for assistance with writing and editing.

Conflict of Interest Declaration: Authors disclose noconflict of interest.

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effect of dietary carbohydrate, fat, and protein on postprandial glycemia and energy intake in cats

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