Energy expenditure and substrate utilization in adults with cystic
fibrosis and diabetes mellitus1,2
Sheila A Ward, Jean L Tomezsko, Douglas S Holsclaw, and Albert M Paolone
ABSTRACT
Background: The onset of cystic fibrosis–related diabetes mel-
litus (CFDM) is often associated with a decline in clinical and
nutritional status.
Objective: The purpose of this study was to characterize energy
expenditure (EE) and substrate utilization during rest, exercise,
and recovery from exercise in patients with CF diagnosed with
diabetes mellitus.
Design: EE, substrate utilization, minute ventilation, tidal vol-
ume, and respiratory rate were calculated by indirect calorimetry
during rest; a 30-min, low-to-medium-intensity exercise bout on
a treadmill; and a 45-min postexercise recovery period (in reclin-
ing position) in 10 CF, 7 CFDM, and 10 control subjects between
18 and 45 y of age.
Results: In all 3 periods, minute ventilation was higher in the CF
and CFDM groups than in the control subjects (P < 0.01). Dur-
ing rest and exercise, the CF and CFDM groups maintained EE
values at the high end of the normal range of the control sub-
jects. However, during recovery, EE was higher in the CF and
CFDM groups than in the control group (P < 0.01).
Conclusions: EE may be higher than usual for the patients with
CF and CFDM during periods of recovery from mild exercise or
activity because of increased work of breathing consistent with
higher ventilatory requirements. This information may be useful
for patients receiving nutritional counseling who may choose to
exercise regularly, but are concerned about possible weight loss.
Am J Clin Nutr 1999;69:913–9.
KEY WORDS Cystic fibrosis, diabetes mellitus, dietary
intake, energy expenditure, oxygen consumption, exercise,
adults, humans
INTRODUCTION
Cystic fibrosis (CF) is the most common, severe genetic dis-
order in the United States. A dramatically improved median age
of survival (29 y) has been reported in recent years (1) because
of advances in a variety of treatment regimens. In addition to
improved antibiotics and respiratory medications, nutritional
care has improved. In conjunction with pancreatic enzyme sup-
plements, a high-energy diet with unrestricted fat has greatly
aided the prevention of growth failure and malnutrition, both of
which have been associated with decreased quality of life and
Am J Clin Nutr 1999;69:913–9. Printed in USA. © 1999 American Society for Clinical Nutrition
survival (2). Management has become even more complicated
with the development of impaired glucose tolerance (26–75% of
patients) and diabetes mellitus (DM) (2.5–12%) probably
because of the destruction of pancreatic tissue. The mean age of
diagnosis for overt diabetes, 19–20 y, is remarkably consistent
and the age of 20 y seems to mark a point of rapid decline in the
survival of patients with CF-related DM (CFDM), with < 25%
reaching the age of 30 y compared with 60% of the nondiabetic
patients with CF (3). Other studies have shown conflicting
results with regard to survival, pulmonary function, and nutri-
tional status (4–6). The Cystic Fibrosis Foundation has outlined
guidelines for CFDM and stressed the complexity of treatment
of a second chronic illness (7).
The struggle to maintain good nutritional status continues
throughout life. Causes of malnutrition and growth failure in CF
are an inadequate energy intake, some malabsorption despite
pancreatic enzyme supplementation, and increased energy
expenditure (EE). EE is the energy used for work and heat pro-
duced by the body to sustain life processes and activity.
Increased EE in patients with CF results from respiratory infec-
tions, inflammation, fever, theorized increased work of breath-
ing, medications, and possibly the basic genetic defect itself.
Loss of glucose energy in the urine, altered metabolism, along
with a possible increased EE can easily put patients with CF and
DM in negative energy balance (8).
This study was undertaken to provide a better understanding
of CFDM and its role in nutritional status. The purpose of this
study was to characterize the EE and pattern of substrate utiliza-
tion of stable ambulatory adult patients with CF and CFDM dur-
ing rest, exercise, and recovery from exercise and to examine
body composition, ventilatory requirements, selected substrates,
and nutrient intakes.
1
From the Pediatric Pulmonary and Cystic Fibrosis Centers, Hahnemann
University Hospital, Philadelphia; the Department of Physical Education,
Temple University, Philadelphia; and the Department of Physical Education
and Exercise Science, Norfolk State University, Norfolk, VA.
2
Address reprint requests to SA Ward, 2401 Corprew Avenue, Echols
Hall, Room 167, Norfolk State University, Norfolk, VA 23504. E-mail:
sward@vger.nsu.edu.
Received November 13, 1997.
Accepted for publication October 20, 1998.
913
914 WARD ET AL
SUBJECTS AND METHODS
Subjects
A total of 27 men and women aged 18–45 y were recruited
and represented 3 study groups. The subjects with CF were
recruited from the CF patient populations at Hahnemann Uni-
versity Hospital, the Medical College of Pennsylvania, and the
University of Pennsylvania Medical Center (all in Philadelphia).
CF patients were grouped according to those without DM (CF
group, n = 3 women and 7 men) and those with DM (CFDM
group, n = 2 women and 5 men). All patients were clinically sta-
ble. No patient with CF was allowed to participate if they were
severely malnourished (≤ 75% of ideal body weight), receiving
supplemental oxygen during the daytime, or taking thyroid or
cardiac medication.
Eight of the 10 subjects in the CF group and all the CFDM
patients were pancreatic insufficient. Eight of the 10 subjects in
the CF group were using bronchodilators, 1 subject was not, and
1 subject’s bronchodilator status was unknown. All CFDM sub-
jects were using bronchodilators. However, on the morning of
the study, use of bronchodilators and all other medications was
not allowed. Of the 10 patients in the CF group, 3 were DF508
homozygous, 4 were DF508 heterozygous (other mutations were
S549N and W1282X with 2 genes unidentified), 2 were
W1282X/3849+10, and 1 was G551D with an unidentified gene.
Of the 7 patients in the CFDM group, 1 was DF508 homozygous
and 5 were DF508 heterozygous (other genes were 621+1 and
R553X with 2 genes unidentified; one was 441 with an unidenti-
fied gene.
Control subjects (n = 5 women and 5 men) were healthy with
no known medical conditions and were recruited from hospital
and community sources. The control group was age- and weight-
matched to the CF and CFDM groups, but not individually so.
The duration of diabetes in the CFDM group was 6 ± 3.9 y and
the CFDM group was significantly older than the control group
(P < 0.03). No persons known to be alcohol or drug addicted or
febrile the morning of the study were allowed to participate. The
study was conducted at Hahnemann University Hospital. All sub-
jects gave written consent and the protocol was approved by the
Committee on Human Subjects, Hahnemann University Hospital.
Study design
The CF, CFDM, and control groups were studied in the early
morning after a 12-h overnight fast. Subjects in the CFDM group
were studied 8–10 h after their last regularly scheduled meal and
evening medication administration. Water was allowed and
encouraged during the fasting period and all medications and
regular therapies, including chest physiotherapy and bron-
chodilators, were withheld. Screening blood glucose tests were
performed and temperatures were taken on the morning of the
study. Patients in the CFDM group were also screened after the
exercise and recovery periods. Measurements were taken for
weight, height, body composition, and lung status. Subjects
reclined quietly and rested for 30 min before baseline measure-
ments of EE, substrate utilization, ventilatory indexes, and
selected blood indexes were made; the same measurements were
made during the exercise and recovery periods. No medications
or therapies, such as bronchodilators, were administered after the
exercise period. For patients in the CFDM group, poststudy
medication was adjusted and given with the poststudy meal
immediately after the study was completed.
Physical characteristics and body composition
Measurements of weight, height, skinfold thicknesses (biceps,
triceps, subscapular, and suprailiac with Lange calipers; Cam-
bridge Scientific Instruments, Cambridge, MD), and midarm cir-
cumference were made in triplicate by one observer (SAW).
Body density (9); percentage body fat, fat mass, and fat-free
mass (FFM; 10); and midarm muscle circumference (11) were
also measured. Percentage ideal body weight (12), body surface
area (by nomogram), and body mass index (13) were calculated.
Ventilatory indexes
Pulmonary function tests were performed with a Spiro Ana-
lyzer ST-90 (Futuremed, Deer Park, NY). The forced vital capac-
ity (FVC) and forced expiratory volume in 1 s (FEV1), which
evaluate the resistance properties of the airways and the strength
of the expiratory muscles, were determined (14). Minute venti-
· · ·
lation (VE), tidal volume (VT), oxygen consumption (VO2), and
respiratory rate (RR) were also measured during the same time
periods and with the same procedure as described for EE.
Blood analyses
Approximately 16 mL blood was drawn from a catheter
inserted into the left brachial vein at the end of the rest, exercise,
and postexercise recovery periods. After centrifugation at 4 8C
for 10–15 min at 2739–5590 3 g (3500–5000 rpm), all blood
samples were separated, stored at 240 8C, and analyzed accord-
ing to hospital laboratory procedures at Hahnemann University
Hospital (glucose, triacylglycerol, and urea) or the General Clin-
ical Research Center at Temple University (catecholamines,
glucagon, and insulin).
Blood drawn for triacylglycerol and urea measurements was
placed in a heparin-containing tube, shaken, and placed on ice
until centrifuged and analyzed with the glycerol phosphate oxi-
dase enzymatic (Boehringer Mannheim, Mannheim, Germany)
and urease method (Boehringer Mannheim), respectively. Blood
samples for glucagon measurements were placed in refrigerated
tubes containing 0.2 mL Trasylol (Bayer, West Haven, CT),
shaken, and placed on ice until centrifuged and analyzed by
radioimmunoassay. Blood samples for catecholamine analyses
were placed in refrigerated Amersham tubes (Piscataway, NJ),
shaken, placed on ice, centrifuged within 15 min, and analyzed
(15). Blood samples for insulin measurements were clotted at
room temperature for 30 min, centrifuged, and analyzed by the
standard double-antibody immunoassay (Pharmacia Diagnostics,
Uppsala, Sweden). Blood samples for glucose measurement were
clotted at room temperature for 15–20 min, centrifuged, and ana-
lyzed by the hexokinase method (Boehringer Mannheim).
Dietary intake
Nutrient intakes were derived from a self-reported dietary
record maintained by the subjects for 3 d before the study day
after they had been given verbal and written instructions. Sub-
jects weighed, measured, and recorded food intakes. All enzyme
supplements for each meal were also recorded. Energy intake
and dietary analyses were conducted by using a computerized
program, NUTRITIONIST III (Salem, OR).
Energy expenditure and substrate utilization
EE and substrate (carbohydrate, fat, and protein) utilization
were calculated from the amount of oxygen utilized and carbon
dioxide produced during 3 time periods on the same day by
 CF, DIABETES MELLITUS, AND ENERGY EXPENDITURE 915

TABLE 1
Physical characteristics, body-composition, resting energy expenditure (REE), and lung function values for the 3 study groups1
CF group CFDM group Control group
Variable (n = 7 M and 3 F) (n = 5 M and 2 F) (n = 5 M and 5 F)
Age (y) 31.1 ± 7.30 33.1 ± 1.762 25.7 ± 4.00
Weight (kg) 63.8 ± 8.46 63.0 ± 12.10 61.8 ± 11.37
Height (cm) 172.4 ± 10.00 169.0 ± 6.23 167.9 ± 9.51
Percentage of IBW (%) 98.5 ± 15.04 104.9 ± 14.09 102.7 ± 11.20
Percentage body fat (%) 19.6 ± 8.02 20.4 ± 6.00 23.1 ± 6.53
Fat-free mass (kg) 51.5 ± 9.87 50.0 ± 9.25 47.9 ± 11.36
Fat mass (kg) 12.2 ± 4.40 13.0 ± 4.77 13.9 ± 3.19
Body mass index 21.4 ± 1.96 21.9 ± 3.29 22.0 ± 2.21
Body surface area (m2) 1.75 ± 0.16 1.71 ± 0.18 1.70 ± 0.20
Skinfold-thickness sum (mm) 42.4 ± 16.94 45.9 ± 16.49 48.2 ± 12.08
REE
(kJ/d) 6774.3 ± 1077.80 6957.6 ± 1459.80 6083.5 ± 1155.62
(kJ ? kg body wt 21 ? d21) 107.1 ± 17.57 112.5 ± 24.69 98.7 ± 9.62
(kJ ? kg FFM 21 ? d21) 134.7 ± 28.03 141.0 ± 26.36 129.3 ± 15.48
Predicted REE (kJ) 6572.6 ± 830.11 6391.9 ± 817.97 6428.3 ± 963.16
Percentage of predicted REE (kJ) 104.0 ± 17.32 109.2 ± 20.15 94.4 ± 7.95
FEV1 (% of predicted) 45.7 ± 15.60 50.3 ± 22.20 95.5 ± 13.703
FVC (% of predicted) 62.6 ± 12.20 64.9 ± 17.10 92.3 ± 14.00
1–
x ± SD. CF, cystic fibrosis; CFDM, CF plus diabetes mellitus; IBW, ideal body weight; FFM, fat-free mass; FEV1, forced expiratory volume in 1 s;
FVC, forced vital capacity.
2
Significantly different from the control group, P < 0.05 (post hoc Tukey-Kramer’s test).
3
Significantly different from the CF and CFDM groups, P < 0.001 (post hoc Tukey-Kramer’s test).

indirect calorimetry with a MetaScope Metabolic Analyzer
(Cybermedic, Boulder, CO). This machine used a paramagnetic
oxygen analyzer and an infrared carbon dioxide analyzer. The
hood flow range was 0–40 L. The machine flow was autoset to
1 of 16 speeds based on 0.5% CO2 and calibrated at the begin-
ning of each subject session. A comfortable one-way valve,
CPAP cushion flex, ventilated mask (Bird Life Design, Dallas)
was worn on the face to cover the mouth and nose while expired
gases were collected and analyzed. In a quiet, thermoneutral
room, EE was measured during rest for 45 min while the subject
reclined comfortably; during a 30-min, low-to-medium-inten-
sity exercise bout (95 kg ? m21 ? min21) on a treadmill; and dur-
ing a 45-min postexercise recovery period (in a reclining posi-
tion). Data for the first 10 min of the resting EE (REE)
measurement were deleted. During the exercise period, the rate
of perceived exertion, heart rate, blood pressure, and oxygen
saturation were monitored. The predicted EE values were cal-
culated by using WHO equations based on age, weight, and sex
(16). Before the study, the reliability and validity of the method
were verified with multiple studies of individual subjects and a
methanol burn test, respectively. A 60-mL urine sample was col-
lected during the study period, from which 24-h urinary urea
excretion was determined to calculate the nonprotein respira-
tory quotient (Hahnemann University Hospital). The respiratory
quotient was calculated as carbon dioxide production divided by
·
VO2, both of which were measured by using the metabolic cart.
Statistical analyses
Substrate utilization, ventilatory indexes, and blood data were
analyzed by using a 3 3 3 factorial analysis of variance
(ANOVA) (version 4.1; SPSS, Inc, Chicago) with repeated
measures across each time period and group. For the initial
analysis of EE between groups (Table 1), multivariate ANOVA
(MANOVA) was used to account for the known effects of sex,
body weight, and body composition in comparisons by group
(17). Specifically, a model was constructed that included sex,
body composition (as FFM), weight, and group (CF, CFDM, and
control groups) in a multiple general linear model procedure. EE
was analyzed by using a repeated-measures (within 3 between,
or mixed) ANOVA model constructed for each transformation of
the dependent variable (Table 2). Contrast testing was per-
formed post hoc for group comparisons in the recovery time
period. A one-way ANOVA with Tukey-Kramer’s test was used
to test for significant differences between groups in age, weight,
height, percentage ideal body weight, percentage body fat, FFM,
fat mass, body mass index, body surface area, and the sum of
skinfold thicknesses. Significance was set at the 0.05 level in all
tests.
RESULTS
The physical characteristics, body composition, baseline and
REE values, and resting lung function of the 3 groups are pre-
sented in Table 1. The diabetic status of the CFDM group was as
follows: stable to well controlled in 5 patients, fair in 1 patient,
and unknown in 1 patient. In the CFDM group, diabetes was
treated with insulin in 6 subjects and with the hypoglycemic
agent Glucotrol (Pratt Pharmaceuticals, New York) in 1 subject.
There were no significant differences in any of the body-compo-
sition or anthropometric data between groups. All 3 groups had
good nutritional status on the basis of mean values for percentage
of ideal body weight. Two subjects in the CF group had mild-to-
moderate malnutrition, one subject in the CFDM group was
underweight, and one control subject had mild malnutrition (12).
EE and substrate utilization
There was no significant difference in EE between the 3 groups
during rest or exercise (Table 2). However, during recovery, EE
916
TABLE 2
Energy expenditure in the 3 study groups during rest, exercise, and recovery1
Energy expenditure CF group (n = 10)
Rest
(kJ/min) 4.7045 ± 0.7489
(kJ ? kg body wt21 ? min21) 0.0745 ± 0.0121
(kJ ? kg FFM21 ? min21) 0.0937 ± 0.0197
Exercise
(kJ/min) 15.9841 ± 2.8911
(kJ ? kg body wt21 ? min21) 0.2531 ± 0.0498
(kJ ? kg FFM21 ? min21) 0.3192 ± 0.0741
Recovery
(kJ/min) 5.0526 ± 0.9330
(kJ ? kg body wt21 ? min21) 0.0795 ± 0.0113
(kJ ? kg FFM21 ? min21) 0.0996 ± 0.0163
1–
x ± SD. CF, cystic fibrosis; CFDM, CF plus diabetes mellitus; FFM, fat-free mass.
2
Significantly different from the CF and CFDM groups, P < 0.01 (post hoc Tukey-Kramer’s test).
was significantly higher in the CF and CFDM groups than in the
control group when measured as kJ/min, kJ ? kg body wt21 ? min21,
and kJ ? kg FFM21 ? min21. There were no significant differences
between the 3 groups in the incremental change of any EE variable
between the rest and exercise periods and between the exercise
and recovery periods. There were no significant differences in any
of the substrate utilization variables between the 3 groups during
exercise or recovery (Table 3). Neither the CF nor the CFDM
groups reached the dietary goal of > 120% of the recommended
dietary allowance for energy or the suggested energy intake from
fat of 35–40% (18, 19).
Ventilatory indexes
Ventilatory indexes during rest, exercise, and recovery are
· ·
presented in Table 4. During rest and exercise, VT, RR, and VO2
21 21
(mL ? kg ? min ) were not significantly different between the 3
·
groups; VE was significantly higher in the CF and CFDM groups
·
than in the control group. During recovery, VT was significantly
higher in the CFDM group than in the control group (P < 0.02)
· ·
and VE and VO2 were significantly higher in the CF and CFDM
groups than in the control group (P < 0.001). There was no signi-
ficant difference in the RR between groups.
Blood indexes
Differences in all of the blood indexes were examined
between the 3 study groups. Glucagon was higher in the CFDM
group (162.5 ± 3.63 ng/L) than in the CF group (102.4 ± 32.3
ng/L) during rest (P < 0.04). Differences in all variables were
also examined within each study group. Within the CF group,
the blood concentration of epinephrine was significantly higher
(P < 0.01) during exercise (3.96 ± 1.93 pmol/L) than during rest
(2.22 ± 1.21 pmol/L). Norepinephrine was also significantly
higher (P < 0.01) during exercise (0.026 ± 0.006 nmol/L) than
during rest (0.015 ± 0.005 nmol/L) and recovery (0.014 ± 0.003
nmol/L). Within the CFDM group, epinephrine was significantly
higher (P < 0.01) during exercise (5.11 ± 3.16 pmol/L) than dur-
ing rest (2.97 ± 1.77 pmol/L) and recovery (3.17 ± 1.41 pmol/L),
and norepinephrine was significantly higher (P < 0.01) during
exercise (0.026 ± 0.011 nmol/L) than during rest (0.017 ± 0.005
nmol/L) and recovery (0.017 ± 0.006 nmol/L). Within the con-
trol group, epinephrine was significantly higher (P < 0.001) dur-
ing exercise (4.57 ± 4.10 pmol/L) than during rest (2.54 ± 2.63
WARD ET AL
CFDM group (n = 7) Control group (n = 10)
4.8317 ± 1.0125 4.2246 ± 0.8033
0.0782 ± 0.0171 0.0686 ± 0.0067
0.0979 ± 0.0180 0.0895 ± 0.0109
15.8992 ± 3.2551 15.0674 ± 2.6275
0.2540 ± 0.0314 0.2498 ± 0.0527
0.3205 ± 0.0464 0.3268 ± 0.0711
5.3497 ± 0.7782 3.7982 ± 0.80332
0.0862 ± 0.0130 0.0619 ± 0.00922
0.1079 ± 0.0117 0.0807 ± 0.01252
pmol/L) and recovery (2.08 ± 1.12 pmol/L), and norepinephrine
was significantly higher (P < 0.001) during exercise
(0.033 ± 0.019 nmol/L) than during rest (0.019 ± 0.009 nmol/L)
and recovery (0.021 ± 0.009 nmol/L). There were no significant
differences in triacylglycerol, urea, insulin, or glucagon across
the 3 time periods (rest, exercise, and recovery) in the CF,
CFDM, and control groups and no significant differences in the
respiratory quotient, the nonprotein respiratory quotient, or glu-
cose variables for the CF and control groups.
In the CFDM group, the respiratory quotient was significantly
higher during exercise than during rest and recovery and signifi-
cantly higher during rest than during recovery (P < 0.04). The
nonprotein respiratory quotient was significantly higher during
rest than during exercise and recovery and significantly higher
during exercise than during recovery (P < 0.03). The blood glu-
cose concentration was significantly higher (P < 0.01) during
rest (8.60 ± 2.90 mmol/L) than during exercise (7.28 ± 1.61
mmol/L) and recovery (7.29 ± 2.09 mmol/L). The percentage
carbohydrate utilization was significantly higher in the CF and
control groups during exercise than during recovery (P < 0.01)
and significantly higher in the CFDM group during exercise than
during rest and recovery (P < 0.01). Within all 3 groups, the per-
centage of protein utilization was significantly lower during
exercise than during rest and recovery (P < 0.001), but there
were no significant differences in the percentage lipid utiliza-
tion. There were also no significant differences in the incremen-
tal changes in substrate utilization between time periods
(between rest and exercise and between exercise and recovery)
across the 3 groups.
DISCUSSION
Both CF groups were well matched in lung disease severity.
There were no significant differences between groups in anthro-
pometric measures, body composition, or nutritional status. In
the recovery phase, EE was significantly higher in the CF and
CFDM groups than in the control group. This difference was
· · ·
supported by higher VE, VT, and VO2 values in the CF and CFDM
groups than in the control group.
The respiratory muscles of patients with CF, regardless of the
presence of diabetes, work harder. The respiratory muscles must
generate more force to provide sufficient oxygen and gas
 CF, DIABETES MELLITUS, AND ENERGY EXPENDITURE 917

TABLE 3 differences between CF patients and matched control subjects in

Substrate utilization in the 3 study groups during rest, exercise, and incremental increases in energy from resting to each of several
recovery1 activities of daily living, including 2 levels of exercise. Although
CF group CFDM group Control group EE was higher (NS) during rest and exercise in the CF and
Variable (n = 10) (n = 7) (n = 10) CFDM groups than in the control group, the CF and CFDM
Rest
groups were able to compensate and maintain EE values within
RQ 0.85 ± 0.04 0.85 ± 0.062 0.83 ± 0.03 the range of those of the control group. Patients with CF and
NPRQ 0.87 ± 0.06 0.90 ± 0.153 0.83 ± 0.04 significant pulmonary involvement have an enlarged physiologic
Carbohydrates (%) 45.0 ± 13.0 39.0 ± 23.3 38.0 ± 11.6 dead space and hypoxemia at rest (21). Physiologic dead space
Lipids (%) 34.5 ± 16.8 33.5 ± 22.3 42.1 ± 13.3 is enlarged because any ventilation to scarred, infected, or
Protein (%) 20.5 ± 12.0 27.5 ± 23.7 19.9 ± 7.4 blocked portions of the lungs is wasted. During exercise in per-
Exercise sons without respiratory distress, the physiologic dead space nat-
RQ 0.85 ± 0.05 0.86 ± 0.034 0.84 ± 0.03 urally decreases (22). If, however, physiologic dead space (not
NPRQ 0.85 ± 0.05 0.86 ± 0.045 0.84 ± 0.04 measured in this study) also decreases during exercise, it might
Carbohydrates (%) 50.6 ± 17.96 52.7 ± 13.57 47.5 ± 11.36
explain why EE variables were not significantly different
Lipids (%) 43.0 ± 18.0 38.7 ± 9.8 46.7 ± 12.6
Protein (%) 6.4 ± 3.78 8.6 ± 6.48 5.8 ± 3.08
between the CF patients and the control subjects during exercise,
Recovery but were significantly different during recovery.
RQ 0.83 ± 0.05 0.82 ± 0.07 0.83 ± 0.05 An elevated REE has been documented in patients with CF (21,
NPRQ 0.84 ± 0.07 0.82 ± 0.09 0.84 ± 0.07 23–27). The REE in normal adults varies greatly, depending on
Carbohydrates (%) 37.7 ± 16.2 38.2 ± 21.4 35.0 ± 16.1 many factors, particularly the amount of metabolically active tis-
Lipids (%) 42.6 ± 20.8 33.3 ± 14.7 44.0 ± 15.1 sue. The range of daily expended energy in severely ill non-CF
Protein (%) 19.7 ± 12.6 28.5 ± 23.1 21.0 ± 9.5 patients varies as well (28). In CF patients, REE appears to
1–
x ± SD. CF, cystic fibrosis; CFDM, CF plus diabetes mellitus; RQ, res- increase as lung function declines (29). In our study, the CF and
piratory quotient; NPRQ, nonprotein respiratory quotient. CFDM groups had subjects with predicted REE values that were
2,5,6
Significantly different from recovery: 2 P < 0.04, 5 P < 0.03, 6 P < 0.01. as high as 130% and 137%, respectively, whereas values in the
3
Significantly different from exercise and recovery, P < 0.03. control group remained within normal limits, the highest predicted
4,7,8
Significantly different from rest and recovery: 4 P < 0.04, 7 P < 0.01, value being 110%. Despite very low pulmonary function, the REE
8
P < 0.001.
of the CF and CFDM groups was not as high as expected. Within
each group, regression analysis of the percentage of predicted
FEV1 was compared with the following indexes: percentage ideal
exchange because of airway obstruction and resistance, such as body weight, percentage of predicted REE, and percentage body
decreased lung compliance. This additional work requires addi- fat. The only significant correlation found was between FEV1 and
·
tional energy. Furthermore, VE was higher in the CF and CFDM percentage body fat in the CF group (r = 0.67, P < 0.05). No
groups to compensate for the ventilation that is wasted because adjustments were made for multiplicity of planned comparisons.
it never reaches the blood (ventilation-to-perfusion mismatch). The most important function of glucagon is to increase blood
No incremental changes in EE were observed between the CF glucose concentrations, mainly via hepatic glycogenolysis and
and CFDM groups and the control group. This finding was con- increased hepatic gluconeogenesis. During rest, the blood
sistent with that of Grunow et al (20), who found no significant glucagon concentration of the CFDM group was significantly

TABLE 4
Ventilatory indexes in the 3 groups during rest, exercise, and recovery1
Variable CF group (n = 10) CFDM group (n = 7) Control group (n = 10)
Rest
·
VE (L/min) 8.5 ± 1.6 8.5 ± 1.5 6.4 ± 1.12
·
VT (mL) 480.0 ± 116.8 464.0 ± 111.3 431.0 ± 142.8
RR (breaths/min) 18.6 ± 5.1 18.8 ± 3.7 15.7 ± 3.6
·
VO2 (mL ? kg21 ? min21) 3.8 ± 0.61 3.9 ± 0.73 3.5 ± 0.37
Exercise
·
VE (L/min) 23.3 ± 4.9 23.7 ± 4.1 18.2 ± 3.02
·
VT (mL) 819.4 ± 197.4 840.4 ± 138.3 762.1 ± 205.8
RR (breaths/min) 29.5 ± 9.0 28.5 ± 5.1 25.1 ± 6.2
·
VO2 (mL ? kg21 ? min21) 12.6 ± 2.5 12.7 ± 1.6 12.5 ± 2.6
Recovery
·
VE (L/min) 8.8 ± 2.0 9.4 ± 1.2 6.0 ± 1.32
·
VT (mL) 472.4 ± 119.1 498.7 ± 100.63 360.6 ± 88.9
RR (breaths/min) 19.5 ± 4.8 19.3 ± 3.6 16.9 ± 2.8
·
VO2 (mL ? kg21 ? min21) 4.1 ± 0.56 4.5 ± 0.78 3.2 ± 0.472
1– · · ·
x ± SD. Normal values based on clinical standards are as follows: VE, 6.0–7.5 L/min; VT, 500 mL; RR, 12–15 breaths/min. VE, minute ventilation;
· ·
VT, tidal volume; RR, respiratory rate; VO2, oxygen consumption; CF, cystic fibrosis; CFDM, CF plus diabetes mellitus.
2
Significantly different from the CF and CFDM groups, P < 0.01 (post hoc Tukey-Kramer’s test).
3
Significantly different from the control group, P < 0.02 (post hoc Tukey-Kramer’s test).
918 WARD ET AL
higher than that of the CF group. Increased glucagon secretions
have been reported in type 1 and type 2 diabetic patients (3) and
in patients with severe diabetic ketoacidosis (30). In patients
with CFDM, glucagon concentrations have been described as
normal or reduced (3, 30). Both hypoglucagonemia and hyper-
glucagonemia have been reported in other studies (31). Kien et
al (32) found elevated hepatic glucose production in children
with CF. The CFDM group in our study had a higher glucagon
concentration than the CF and control groups during rest (P <
0.05), exercise (NS), and recovery (NS). The blood glucagon
concentration in the CFDM group was possibly higher during
rest to guard against hypoglycemia because neither decreased
plasma insulin concentrations nor increased fat oxidation were
observed after the overnight fast. The latter condition indicates a
low blood glucose concentration or a shift in substrate utiliza-
tion, which would stimulate the release of glucagon. However,
because of the large number of variables measured in the blood
profile and the small sample size, conclusions based on glucagon
data must be made with caution.
The CFDM group tended to have a higher epinephrine con-
centration than the other 2 groups at the end of each study
period. In addition, epinephrine concentrations in the CF and
CFDM groups remained higher than baseline values at the end of
the recovery period, whereas the control group had an epineph-
rine concentration that was lower than baseline at this time point.
Despite these trends, no significant differences were found in
epinephrine concentrations between the 3 groups and there was
great variability in the catecholamine data. Catecholamines may
serve as indicators of stress and are known to increase the basal
metabolic rate by 7–15%, increase glucagon, decrease insulin
production, increase glucose production by the liver (gluconeo-
genesis), increase glycogenolysis, and increase lipolysis. In
addition, chronically elevated epinephrine concentrations result
in hyperglycemia and fat store depletion. In this study, we were
unable to conclude that circulating catecholamines in the CFDM
group contributed to the increased EE found during recovery. In
one study, adult patients with CF (without DM) were found to
have significantly higher epinephrine concentrations than con-
trol subjects (33). We hypothesized that chronically elevated epi-
nephrine concentrations in patients with CF and CFDM may
result in increased EE, hyperglycemia, increased fat store deple-
tion, and poor nutritional status. We believe these observed
trends in epinephrine need further study.
This study was not designed specifically with the power to
detect group differences in any particular index; thus, inferences
about nonsignificant comparisons are particularly susceptible to
type II errors. For instance, mean within-group EEs at rest and
during exercise were not significantly different in the present
study; however, these results were subject to type II error and
thus should be interpreted with caution. On the other hand, these
same comparisons may indicate trends that should be investi-
gated in larger-scale studies not susceptible to type II error.
In this study, patients with CF and CFDM were able to main-
tain EE values within the normal range of the control group dur-
· joint FAO/WHO/UNU Expert Consultation. World Health Organ
ing rest and exercise periods, despite a significantly higher VE.
However, during recovery from exercise, the CF and CFDM
groups used more energy than the control group and not only
· ·
maintained a higher VE, but a higher VO2 as well. Our data sug-
gest that the elevated EE in both the CF and CFDM patients, dur-
ing periods of recovery from mild exercise or activity, was due to
increased breathing resulting from higher ventilatory require-
ments to compensate for a ventilation-to-perfusion mismatch.
This additional energy requirement should be considered by CF
and CFDM patients who choose to exercise regularly and should
be incorporated into nutritional counseling goals intended for
these patients. Some patients express concern about weight loss
from exercise. Accurate assessments of energy use patterns in CF
patients, which may differ from those in persons without CF, will
allow patients to exercise comfortably, receive health benefits
associated with regular exercise, and adjust their daily energy
intake to compensate for the additional energy requirement dur-
ing exercise recovery. Further studies of the energy requirements
of patients with CF or CFDM during recovery periods postexer-
cise, with larger sample sizes and more in-depth blood analyses
(eg, of fatty acids, glycerol, lactate, glucagon, and epinephrine
concentrations), are needed to advance the understanding of EE
in these patients.
We thank Lisa Davis for her dedicated assistance and Kevin B Stansberry
for statistical assistance.
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