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[A1CR]

It appears that exercise or CR weight loss provide many of
the same
benefits. Exercising to the extent necessary for the weight
loss that can
be achieved via CR and the benefits of such CR may not be
possible via
exercise, and, I believe, CR is so much more tolerable that
extreme
exercise.

Weiss EP, Racette SB, Villareal DT, Fontana L, Steger-May K,
Schechtman KB,
Klein S, Holloszy JO.
Improvements in glucose tolerance and insulin action induced
by increasing
energy expenditure or decreasing energy intake: a randomized
controlled
trial.
Am J Clin Nutr. 2006 Nov;84(5):1033-1042.
PMID: 17093155

BACKGROUND: Weight loss, through calorie restriction or
increases in energy
expenditure via exercise, improves glucose tolerance and
insulin action.
However, exercise-induced energy expenditure may further
improve
glucoregulation through mechanisms independent of weight
loss. OBJECTIVE:
The objective was to assess the hypothesis that weight loss
through
exercise-induced energy expenditure improves glucoregulation
and circulating
factors involved in insulin action to a greater extent than
does similar
weight loss through calorie restriction. DESIGN: Sedentary
men and women
aged 50-60 y with a body mass index (kg/m(2)) of 23.5-29.9
were randomly
assigned to 1 of 2 weight-loss interventions [12 mo of
exercise training (EX
group; n = 18) or calorie restriction (CR group; n = 18)] or
to a healthy
lifestyle (HL) control group (n = 10). The insulin
sensitivity index and
areas under the curve for glucose and insulin were assessed
with an
oral-glucose-tolerance test. Adiponectin and tumor necrosis
factor alpha
concentrations were measured in fasting serum. Fat mass was
measured by
dual-energy X-ray absorptiometry. RESULTS: Yearlong energy
deficits were not
significantly different between the EX and CR groups, as
evidenced by body
weight and fat mass changes. The insulin sensitivity index
increased and the
glucose and insulin areas under the curve decreased in the
EX and CR groups,
remained unchanged in the HL group, and did not differ
significantly between
the EX and CR groups. Marginally significant increases in
adiponectin and
decreases in the ratio of tumor necrosis factor alpha to
adiponectin
occurred in the EX and CR groups but not in the HL group.
CONCLUSIONS:
Weight loss induced by exercise training or calorie
restriction improves
glucose tolerance and insulin action in nonobese, healthy,
middle-aged men
and women. However, it does not appear that exercise
training-induced weight
loss results in greater improvements than those that result
from calorie
restriction alone.

... Men and women aged 50-60 y with a body mass index (BMI;
in kg/m2) of
23.5-29.9 ... randomly assigned (stratified by sex) to 1 of
2 weight-loss
interventions [12 mo of exercise energy expenditure (EX
group; n = 18) or
calorie restriction (CR group; n = 18)] or to a healthy
lifestyle (HL)
control group (n = 10). Although the selection criterion
included the high
end of the range for normal BMI, only 9 enrolled subjects (5
in the EX group
and 4 in the CR group) had a BMI < 25.0. Candidates for the
study were
excluded if they had a history of diabetes or a fasting
blood glucose value
126 mg/dL; a history or clinical evidence of coronary artery
disease,
stroke, or lung disease; a resting blood pressure 170 mm Hg
(systolic) or
100 mm Hg (diastolic); or a recent history or evidence of
malignancy.
Furthermore, all candidates had to be nonsmokers, had to be
sedentary
(defined as exercising <20 min/d, twice per week, during the
6 mo before
baseline testing), and had to not be taking medications that
could affect
study outcomes. The women had to be postmenopausal. ...

... The objective of the calorie restriction intervention
was to decrease
calorie intake by 16% during the first 3 mo and by 20%
during the remaining
9 mo. The initial calorie intake was assumed to be equal to
total daily
energy expenditure (TEE) as determined by the doubly labeled
water (DLW)
method over 2 consecutive 2-wk assessment periods. Calorie
intake
prescriptions were calculated as baseline TEE minus the
desired magnitude of
calorie restriction (ie, 16% or 20% of TEE). The
participants met with the
study dietitians weekly, at which time body weight was
measured and
consultation was provided to maximize compliance with the
prescribed calorie
restriction. The participants frequently recorded their food
consumption.
The dietitians used these records, qualitatively, as a basis
for
personalized dietary changes that would help the
participants achieve the
prescribed calorie restriction. The general strategy was to
encourage
reductions in portion size and to substitute foods with a
low calorie
density with those with a high calorie density.

... The goal of the exercise training intervention was to
induce the same
calorie deficit as was induced by the calorie restriction
intervention by
holding energy intake constant at baseline levels and
increasing exercise
energy expenditure by 16% of baseline TEE for the first 3 mo
and by 20% for
the subsequent 9 mo. Exercise energy expenditure goals were
given to the
participants during weekly meetings with exercise trainers.
The participants
exercised, either in our facility or on their own, while
using wrist
watch-type heart rate (HR) monitors (S610; Polar Electro Oy,
Kempele,
Finland) that stored exercise-specific data for gross energy
expenditure,
HR, exercise duration, and the number of exercise sessions
performed.
Maximal oxygen uptake (V^O^2^max), maximal HR, and body
weight, which the
monitors use to estimate gross energy expenditure, were
measured and updated
every 3 mo. Because the study goals were based on net
exercise energy
expenditure, whereas the Polar HR monitors quantified gross
energy
expenditure, the number of calories that would have been
expended during the
exercise time, if the participant did not exercise, was
added to the net
exercise energy expenditure goal. ...

... Participants in the HL group did not receive
instructions to change
either exercise or diet behaviors. These participants were
offered advice
for eating a healthy diet, but only if they requested it.
Furthermore, all
HL group participants were provided with passes to offsite
yoga classes to
use as they desired. Although the frequencies of dietary
consultations and
yoga class attendance were not documented, both were minimal.

... RESULTS ... Participants ... Sample sizes for
recruitment and for each
stage and arm of the study are diagramed in Figure 1. Of the
48 participants
who started the study, 2 dropped out before the follow-up
OGTT and were
therefore not included in the analyses for the present
report. Sex and
racial group representations were not different in the EX,
CR, and HL
groups: 67%, 61%, and 60% female, respectively (P = 0.92)
and 89%, 94%, and
70% white, respectively (P = 0.32). Participants in the EX
group were
slightly older than those in the CR (P = 0.0006) and HL (P =
0.02) groups
(59±3, 55±3, and 56±3 y, respectively). Inclusion of age as
a covariate in
the outcome analyses did not affect the study findings (data
not shown);
therefore, age was not included as a covariate in the
reported data.

... Physical activity, as assessed with the 7-d PAR,
increased from baseline
during the intervention in the EX group and remained
unchanged in the CR and
HL groups (Figure 2). The interaction between group and time
for physical
activity levels was significant (P = 0.0497) after baseline
physical
activity levels were accounted for. ... significantly
different ... energy
intake measured by the doubly labeled water (DLW) method and
dual-energy
X-ray absorptiometry (DXA) (P = 0.01), and energy intake
measured with a
food diary (P = 0.003) by repeated-measures mixed-model
ANOVAs that included
baseline values as a covariate. ...

... According to HR monitor data, net exercise energy
expenditure for
participants in the EX group averaged 228±131 kcal/d over
the 12-mo
intervention, and this was accomplished in 5.8±2.5 exercise
sessions per
week at an average exercise duration of 62±18 min per
session. These
estimates of exercise quantity are conservative because the
participants did
not record 13.5±16.8% of the exercise sessions on the HR
monitors according
to the weekly questionnaires. Exercise intensity was 71±9%
of maximal HR
measured during the most recent V^O^2^max test. Walking,
elliptical machine
exercise, cycling, and running were the most common
exercises performed.

Aerobic capacity ... Baseline V^O^2^max did not differ
significantly
between the EX, CR, and HL groups, whether expressed in
absolute terms or
relative to body weight (Table 1). V^O^2^max increased from
baseline to 12
mo in the EX group, whether expressed in absolute or
relative terms (Table
1). V^O^2^max decreased from baseline to 12 mo in the CR
group; however,
this reduction was more than fully offset by the reduction
in body weight
such that relative V^O^2^max) increased by the end of the
intervention
(Table 1). Neither absolute nor relative V^O^2^max changed
from baseline to
12 mo in the HL group (Table 1).

TABLE 1 Aerobic capacity before and after the intervention^1
================================================
---Group---P^3
---EX (n = 16)^2 CR (n = 17)^2 HL (n = 9)^2---
================================================
V^O^2^max (mL/min) - - - <0.0001
Baseline 1969±591^4 2111±527 2183±685
Final 2265±726^5 1995±569 2062±641
Change 296±272^6 -116±121^6 -122±237
V^O^2^max (mL/kg/min) - - - <0.0001
Baseline 25±6 27±4 26±5
Final 32±9^5 28±5 25±5
Change 7±5^6 2±2^6 -1±3
================================================
1 EX, exercise training; CR, calorie restriction; HL,
healthy lifestyle
(control); V^O^2^max, maximal oxygen uptake. None of the
baseline values
were significantly different between groups (ANOVA).
2 Sample sizes reflect missing data as a result of
technical problems
during testing.
3 Reflects the significance of the between-group
differences in final
values for each outcome after adjustment for baseline values
(ANCOVA).
4 Arithmetic chi^2±SD (all such values).
5 Significantly different from the CR and HL groups P
</= 0.05 (paired t
test).
6 Significantly different from zero, P </=0.05 (paired t
test).

Energy intake ... According to DLW-based estimates, energy
intake during
the intervention in the EX and HL groups was not
significantly different
from baseline (Figure 2). Energy intake in the CR group was
significantly
lower than baseline during months 0-9. During the last 3 mo
of the study,
energy intake in the CR group was not significantly
different from baseline
(P = 0.10). The interaction between group and time for the
DLW-based
estimates of energy intake was significant (P = 0.01) after
baseline energy
intake was accounted for.
According to the 7-d food records, calorie intake in the EX
and HL groups
was not significantly different from baseline during the
intervention.
Energy intake in the CR group was lower than baseline at all
time points
during the intervention (Figure 2). The interaction between
group and time
for the food record-based estimates of energy intake was
significant (P =
0.003) after baseline energy intake was accounted for.

Body weight and composition ... Total body weight, BMI,
total fat mass,
truncal fat mass, and abdominal fat mass all decreased in
the EX and CR
groups but remained unchanged in the HL group (Table 2). As
a result, the
final values for weight and all of the body-composition
measures were lower
in the EX and CR groups than in the HL group after
adjustment for baseline
values. Body weight did not change during the 3 wk before
the final OGTT in
either the EX group (3 wk before the OGTT: 70.4±9.6 kg; day
of the OGTT:
69.8±9.0 kg) or the CR group (3 wk before the OGTT:
70.7±11.0 kg; day of the
OGTT: 70.8±11.0 kg).

TABLE 2 Body weight and body composition before and after
the intervention^1
================================================
---Group---P^3
---EX (n = 18)^2 CR (n = 18)^2 HL (n = 10)^2---
================================================
Weight (kg) - - - 0.0003
Baseline 76.5±10.5^3 78.9±9.4 81.9±11.3
Final 69.9±8.9^4 70.6±11.1^4 80.7±12.3
Change -6.6±5.5^5 -8.2±4.8^5 -1.2±2.1
BMI (kg/m2) - - - 0.0002
Baseline 27.1±1.9 27.1±2.5 27.9±1.3
Final 24.8±2.6^4 24.2±2.8^4 27.4±1.8
Change -2.3±1.7^5 -2.9±1.7^5 -0.5±0.8
Total fat mass (kg) - - - 0.0009
Baseline 25.7±5.7 26.4±5.4 26.5±3.3
Final 20.1±7.6^4 20.1±6.7^4 26.2±3.3
Change -5.6±4.9^5 -6.3±3.8^5 -0.4±1.7
Trunk fat mass (kg) - - - 0.004
Baseline 13.0±3.0 13.4±3.2 14.0±2.2
Final 9.7±4.0^4 9.9±3.8^4 13.8±2.7
Change -3.3±3.1^5 -3.5±2.2^5 -0.2±0.9
Abdominal fat mass (kg) - - - 0.009
Baseline 7.9±1.9 8.5±2.0 8.2±1.3
Final 6.0±2.6^6 6.4±2.6^6 8.2±1.5
Change -1.9±2.1^7 -2.1±1.6^7 -0.02±0.7
================================================
1 EX, exercise training; CR, calorie restriction; HL,
healthy lifestyle
(control). For brevity, body-composition data are presented
only for
baseline and the final time points. None of the baseline
values were
significantly different between groups (ANOVA). Tukey's
tests were used for
all post hoc comparisons between groups; ANCOVA was used for
abdominal fat
mass because it was measured only at the beginning and end
of the study (all
other body-composition variables were measured at 6 time
points).
2 Reflects the significance of the interaction between
study group and
time, except for abdominal fat mass, in which it reflects
the significance
of the between-group comparison of final values after
adjustment for
baseline values by ANCOVA.
3 Arithmetic chi^2±SD (all such values).
4,6 The change from baseline was significantly different
from that in the
HL group: 4 P </=0.05 (mixed-model repeated-measures ANOVA),
6 P </=0.05
(ANCOVA that included baseline values as the covariate).
5,7 Significantly different from zero: 5 P </=0.05
(mixed-model
repeated-measures ANOVA), 7 P </=0.05 (paired t test).

Body weight, total fat mass, energy intake, aerobic
capacity, and physical
activity data are included as indicators of compliance and
to help in the
interpretation of results for the primary outcomes. ...

Insulin action and OGTT insulin concentrations ... ISI
increased in the
exercise and CR groups but not in the HL group. As a result,
and after
adjustment for baseline values, ISI was greater in the EX
and CR groups than
in the HL group at the end of the intervention (Table 3).
The final adjusted
ISI means were not different between the exercise and CR
groups. Likewise,
fasting insulin and insulin AUC decreased in the EX and CR
groups but not in
the HL group, such that the final adjusted values were
significantly lower
in the EX and CR groups than in the HL group. Because of
baseline
differences in ISI, we evaluated the OGTT insulin data after
adjusting for
baseline ISI; however, this did not change the statistical
significance of
the findings for OGTT insulin.

TABLE 3 Indexes of glucose tolerance and insulin action
before and after the
intervention^1
================================================
---Group---P^3
---EX (n = 18)^2 CR (n = 18)^2 HL (n = 10)^2---
================================================
ISI^4,5 - - - 0.001
Baseline 4.5±2.3^6 7.7±4.8 4.2±2.8
Final 7.4±2.9^7 9.7±3.7^7 4.5±2.9
Change 3.0±2.7^8 2.0±3.9^8 0.3±1.4
Fasting insulin (µU/mL)^4 - - - 0.01
Baseline 8.2±4.7 6.8±6.1 9.0±3.4
Final 5.6±3.7^7 4.4±2.8^7 10.3±5.3
Change -2.7±5.0^8 -2.5±3.9^8 1.3±3.2
Insulin AUC (×10^3 µU × min/mL) - - - 0.001
Baseline 9.1±4.5^9 5.5±2.9 10.2±4.79
Final 5.7±2.9^7 4.2±1.5^7 8.8±3.6
Change -3.4±3.0^8 -1.3±2.1^8 -1.4±2.1
Fasting glucose (mg/dL) - - - 0.06
Baseline 96.1±5.8 94.7±8.7 94.0±9.2
Final 94.7±6.4 89.4±7.3 92.1±10.4
Change -1.4±4.6 -5.3±6.3 -1.9±6.5
Glucose AUC (×10^3 mg × min/dL)^10 - - - 0.11^11
Baseline 18.4±2.5 18.4±3.4 17.6±3.4
Final 16.0±1.9 15.9±2.2 16.9±3.0
Change -2.4±2.5 -2.5±2.5 -0.7±1.5
================================================
1 ISI, insulin sensitivity index determined according to
Matsuda and
DeFronzo (13); AUC, total area under the curve; EX, exercise
training; CR,
calorie restriction; HL, healthy lifestyle (control).
2 Nonfasting insulin data are missing for one
participant because of
technical errors during data collection.
3 Reflects the significance of the between-group
differences in final
values for each outcome after adjustment for baseline values
(ANCOVA).
4 Data were log transformed for data analyses.
5 ANOVA indicated significant differences between groups
for baseline
ISI; however, post hoc Tukey's tests indicated only
marginally significant
differences between the EX and CR groups and between the HL
and CR groups
(both P = 0.06) and no significant differences between the
EX and HL groups.
6 Arithmetic chi^2±SD (all such values).
7 Significantly different from the HL group, P 0.05
(baseline-adjusted
final values by ANCOVA and Tukey's tests).
8 Significantly different from zero, P </=0.05 (paired t
test).
9 Significantly different from the CR group, P </=0.05
(ANOVA and Tukey's
test).
10 The within-group decreases in glucose AUC were
significant in the EX
and HL groups, P </= 0.05 (paired t test).
11 Addition of baseline ISI as a covariate resulted in a
significant
between-group effect (P = 0.03), and post hoc Tukey's tests
showed
significant differences in final-adjusted glucose AUC values
for comparisons
between the EX and HL groups and between the CR and HL groups.

Oral glucose tolerance ... Although fasting glucose
decreased in the CR
group but not in the EX or HL group, the final fasting
glucose values were
not significantly different between the groups after
adjustment for baseline
values (Table 3), and these results were unaffected after
baseline ISI was
included as a covariate. Final glucose AUC values were not
significantly
different between study groups after adjustment for baseline
values.
However, after baseline ISI was added as a covariate, the P
value of 0.11
for glucose AUC (Table 3) became significant (P = 0.03) and
there were
significant differences between both intervention groups and
the control
group.

Adiponectin, TNF-alphaalpha, cortisol, and FFA ... Serum
adiponectin
concentration tended to increase in the exercise (P = 0.06)
and the CR (P =
0.07) groups and decreased significantly in the HL group (P
= 0.05) (Table
4). At the end of the intervention, adiponectin
concentrations were higher
in the EX and CR groups than in the HL group but were not
significantly
different between the EX and CR groups. Final adjusted serum
TNF-alphaalpha
concentrations were not significantly different between
study groups. The
ratio of TNF-alphaalpha to adiponectin tended to decrease in
the EX group (P
= 0.06), decreased significantly in the CR group, but
remained unchanged in
the HL group. As a result, the final adjusted ratios of
TNF-alphaalpha to
adiponectin were significantly lower in the EX and CR groups
than in the HL
group. Final ratios of TNF-alphaalpha to adiponectin were
not significantly
different between the EX and CR groups. Final serum cortisol
concentrations,
after adjustment for baseline values, did not differ
significantly between
the 3 study groups. Serum FFAs did not change significantly
in any of the
study groups, and the final adjusted values were not
significantly different
between groups. None of the statistical results for the
outcomes reported in
Table 4 were affected by the inclusion of baseline ISI as a
covariate.

TABLE 4 Circulating serum adiponectin, tumor necrosis factor
(TNF-alphaalpha), cortisol, and free fatty acid (FFA)
concentrations before
and after the intervention^1
================================================
---Group---P^2
---EX (n = 18) CR (n = 18) HL (n = 10)---
================================================
Adiponectin (µg/mL) - - - 0.005
Baseline 11.0±3.83 13.3±6.8 8.6±3.0
Final 12.9±4.74 15.5±6.84 6.7±1.6
Change 1.9±4.0 2.2±4.7 -1.9±2.65
TNF-alphaalpha (pg/mL) - - - 0.53
Baseline 1.34±0.70 1.13±0.52 1.17±0.89
Final 1.09±0.56 0.93±0.46 1.11±0.70
Change -0.25±0.56 -0.20±0.26 -0.06±0.41
TNF-alphaalpha:adiponectin (x10-8) - - - 0.0009
Baseline 13.2±7.7 11.0±6.7 13.8±7.9
Final 10.1±7.34 7.2±4.04 15.7±6.5
Change -3.0±6.4 -3.9±4.15 1.9±5.2
Cortisol (µg/mL) - - - 0.30
Baseline 11.9±4.1 15.4±4.76 12.8±2.7
Final 11.8±4.9 11.4±3.2 10.6±3.1
Change -0.1±4.4 -4.0±4.1 -2.2±4.2
FFA (µmol/L) - - - 0.39
Baseline 646±210 569±231 603±207
Final 586±254 501±203 616±175
Change -60±336 -68±306 13±152
================================================
1 EX, exercise training; CR, calorie restriction; HL,
healthy lifestyle
(control).
2 Reflects the significance of the between-group
differences in final
values for each outcome after adjustment for baseline values
(ANCOVA).
3 Arithmetic chi^2±SD (all such values).
4 Significantly different from the HL group, P </=0.05
(baseline-adjusted
final values by ANCOVA and Tukey's tests).
5 Significantly different from zero, P 0.05 (paired t
test).
6 Significantly different from the EX group, P </=0.05
(ANOVA and Tukey's
test).

To gain insight into the mechanism of improvements in ISI
that resulted from
exercise and calorie restriction, the correlations between
changes in ISI,
after accounting for the effects of baseline ISI, and the
changes in
adiponectin, TNF-alpha, and the ratio of TNF-alpha to
adiponectin, were
assessed. No significant difference (P = 0.37) was evident
between the EX
and CR groups with respect to the correlations between
change in adiponectin
and the change in ISI (EX group: r = 0.47; CR group: r =
0.17). Likewise,
the correlations for change in TNF-alpha and change in ISI
were not
significantly different (P = 0.06) between groups (EX group:
r = -0.34; CR
group: r = 0.33). In contrast, the correlation between the
change in the
ratio of TNF-alpha to adiponectin and the change in ISI was
stronger in the
EX group (r = -0.67, P = 0.005) than in the CR group (r =
0.005, P = 0.98);
P = 0.03 for the comparison between the EX and CR groups
(Figure 3). ...

... In summary, data from the present study suggest that
exercise
training-and calorie restriction-induced weight loss are
effective means for
improving glucose tolerance and insulin action in nonobese,
healthy,
middle-aged men and women. It does not appear that exercise
training-induced
weight loss provides benefits above and beyond those that
can be achieved by
calorie restriction alone if exercise training is
discontinued for 2 d.