Effect of Exercise on Total and Intra-abdominal Body Fat in Postmenopausal Women A Randomized Controlled Trial Context The increasing prevalence of obesity is a major public health concern. Physi-
cal activity may promote weight and body fat loss. Objective To examine the effects of exercise on total and intra-abdominal body fat overall and by level of exercise. Design Randomized controlled trial conducted from 1997 to 2001. Setting and Participants A total of 173 sedentary, overweight (body mass index
Ն24.0 and Ͼ33% body fat), postmenopausal women aged 50 to 75 years who were
Intervention Participants were randomly assigned to an intervention consisting of exercise facility and home-based moderate-intensity exercise (n=87) or a stretching Main Outcome Measure Changes in body weight and waist and hip circumfer-
ences at 3 and 12 months; total body, intra-abdominal, and subcutaneous abdominal
US adult population isoverweight or obese,1 and
Results Twelve-month data were available for 168 women. Women in the exercise
group participated in moderate-intensity sports/recreational activity for a mean (SD)
of 3.5 (1.2) d/wk for 176 (91) min/wk. Walking was the most frequently reportedactivity. Exercisers showed statistically significant differences from controls in baseline
to 12-month changes in body weight (–1.4 kg; 95% confidence interval [CI], –2.5 to
eases, including coronary heart disease,2
–0.3 kg), total body fat (–1.0%; 95% CI, –1.6% to –0.4%), intra-abdominal fat
type 2 diabetes,3 hypertension,4 stroke,5
(–8.6 g/cm2; 95% CI, –17.8 to 0.9 g/cm2), and subcutaneous abdominal fat
(–28.8 g/cm2; 95% CI, –47.5 to –10.0 g/cm2). A significant dose response for greater
body fat loss was observed with increasing duration of exercise. Conclusions Regular exercise such as brisk walking results in reduced body weight
and body fat among overweight and obese postmenopausal women.
of preventing weight gain and promot-ing maintenance of weight loss in over-
Author Affiliations: Department of Epidemiology and
Public Health, Yale University School of Medicine, NewHaven, Conn (Dr Irwin); Cancer Prevention Research
Program, Fred Hutchinson Cancer Research Center (Drs
Yasui, Ulrich, Bowen, Rudolph, Potter, and McTiernan
and Ms Aiello), and Departments of Epidemiology (DrsUlrich, Potter, and McTiernan) and Internal Medi-
cine (Drs McTiernan, Rudolph, and Yukawa), Univer-
sity of Washington, Seattle; and Department of In-
ternal Medicine, Division of Geriatric Medicine,University of Colorado Health Sciences Center, Den-
Corresponding Author and Reprints: Anne McTiernan, MD, PhD, Fred Hutchinson Cancer Research Center,
1100 Fairview Ave N, MP-900, Seattle, WA 98109-
2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, January 15, 2003—Vol 289, No. 3 323
EXERCISE AND BODY FAT IN POSTMENOPAUSAL WOMEN
Participants
sis of diabetes and had fasting blood glu-
physiologist at a facility (University of
been published elsewhere.11 After a tele-
intensity recreational activity and maxi-
baseline clinic visits (a physical exami-
assessment, and dual-energy x-rayabsorptiometry [DXA] and computedtomography [CT] scans). After fur-
Figure 1. Recruitment of Participants Into the Physical Activity for Total Health Study
ther determining eligibility and studyinterest, we randomly assigned 173
tion (n = 87) or the control group (n = 86) (FIGURE 1). Randomization
eration and group assignment wasplaced in a sealed envelope, which was
Baseline and Follow-up Measures We collected demographic and medi-
cal history information at baseline andat 3- and 12-month visits. We mea-
months, and 12 months via a 120-item self-administered food frequency
physical activity at baseline, 3 months,and 12 months among exercisers and
during the past 3 months. For the ac-tivities performed, the women re-
corded the number of days per weekand minutes per session.324 JAMA, January 15, 2003—Vol 289, No. 3 (Reprinted) 2003 American Medical Association. All rights reserved.
EXERCISE AND BODY FAT IN POSTMENOPAUSAL WOMEN
and maintain joint stability. A variety
ing a lateral-view radiograph of the skel-
creased every 2 minutes (eg, stage 2: 3.5
and with a slice thickness of 8 mm). Measure of Exercise Adherence
and computing the circumscribed areas.
kept daily activity logs of all sports or
recreational activities they performed. Exercise Intervention
intensity exercise 5 d/wk for 12 months.
were taken in duplicate and averaged.
cilities and to exercise 2 d/wk at home.
intensity sports/recreational exercise).
at the facility if they chose). The train-
Intervention Strategies
ized attention in facility classes; group ex-
mill walking and stationary bicycling. Statistical Analysis
curls, leg press, chest press, and seated
2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, January 15, 2003—Vol 289, No. 3 325
EXERCISE AND BODY FAT IN POSTMENOPAUSAL WOMEN
Table 1. Baseline Characteristics of Randomized Participants in the Physical Activity for Total
control groups were similar (TABLE 1). Exercisers Controls
different activities (TABLE 2). Heart rate
ercise intervention (all after 3 months);
Subcutaneous abdominal body fat, g/cm2 (CT)
Total energy intake, mean (95% CI), kcal/d‡
Maximal oxygen consumption, mean (95% CI),
Abbreviations: CI, confidence interval; CT, computed tomography; DXA, dual-energy x-ray absorptiometry. *None of the comparisons between baseline characteristics of intervention and control participants were statistically
†Body mass index is calculated as weight in kilograms divided by the square of height in meters.
‡Calculated from food frequency questionnaire.
baseline in body composition for both groups are shown in TABLE 3. After 12
months, exercisers lost an average of 1.3
in controls (P=.01). The exercise group
trol group (P = .045). Statistically sig-
ues in the intent-to-treat analysis.
body weight (P=.05), BMI (P=.04), and
hip circumference (P = .01) occurred
over time (PϽ.05 for trend), with
served at 12 months than at 3 months.
control participants, stratified by age and
BMI at baseline, is shown in TABLE 4.
12 months did not vary by age or BMI. 326 JAMA, January 15, 2003—Vol 289, No. 3 (Reprinted) 2003 American Medical Association. All rights reserved.
EXERCISE AND BODY FAT IN POSTMENOPAUSAL WOMEN
and stratified by tertiles of duration and
level, are shown in FIGURE 2. Women
who exercised for more than 195min/wk (highly active) lost 4.2% of totalbody fat compared with losses of 2.4%
Table 2. Types of Physical Activity Recorded Among Exercisers (n = 87) in Daily Activity Logs Maximum Heart Rate %, Activity Type Observations, No. (%) Mean (SD) [Range]* At the Facility
level, is shown in FIGURE 3. Women
*Maximum heart rate percentage = (maximum heart rate max from graded exercise test − exercise heart rate)/
†Strength training included leg press, leg extension, leg curls, bench press, and seated dumbbell row. ‡Calisthenics included conditioning and floor exercises.
§Other activities were performed at a frequency of less than 0.1%. Table 3. Change in Body Composition Measures at 3 and 12 Months in Exercise Intervention and Control Participants Mean (95% Confidence Interval) P Value for P Baseline vs 3 mo Baseline vs 12 mo Difference Value Exercisers Controls Difference Exercisers Controls Difference Baseline Trend*
−155 (−250 to −60) −151 (−246 to −55)
Abbreviations: CT, computed tomography; DXA, dual-energy x-ray absorptiometry; NA, not applicable. *Test for trend in between-group differences over time (ie, baseline vs 3 and 12 months). †Body mass index is calculated as weight in kilograms divided by the square of height in meters. ‡Calculated from food frequency questionnaire. 2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, January 15, 2003—Vol 289, No. 3 327
EXERCISE AND BODY FAT IN POSTMENOPAUSAL WOMEN
in prolonged and increasing benefits.
tistically significant between-group dif-
Table 4. Change in Body Composition Measures at 12 Months in Exercise Intervention Participants Stratified by Age and Body Mass Index at Baseline Mean (95% Confidence Interval) Baseline Baseline vs 12 mo P Value for Exercisers Exercisers Controls Exercisers Controls Difference vs Controls Age at Baseline, y*
140.7 (121.9 to 159.6) 142.4 (123.8 to 161.0)
157.8 (133.3 to 182.2) 161.9 (142.6 to 181.3) −19.0 (−31.1 to −6.9)
149.6 (112.8 to 186.4) 132.3 (102.1 to 162.5)
401.4 (359.1 to 443.7) 366.3 (335.6 to 397.1) −12.3 (−26.3 to 1.7)
380.5 (338.8 to 422.1) 398.6 (336.0 to 461.2) −33.3 (−64.4 to −2.3)
366.8 (312.1 to 421.5) 321.9 (257.7 to 386.1) −28.0 (−66.1 to 10.0)
Body Mass Index at Baseline†
117.5 (100.1 to 134.8) 135.4 (114.7 to 156.2)
179.1 (160.9 to 197.3) 171.9 (152.5 to 190.3) −10.4 (−21.6 to 0.8)
300.9 (266.3 to 335.4) 278.4 (237.1 to 319.8) −16.6 (−31.9 to −1.3)
347.1 (304.4 to 389.8) 339.4 (311.0 to 367.7) −30.7 (−54.8 to −6.6)
456.5 (421.0 to 492.0) 433.3 (389.5 to 477.1) −19.0 (−42.5 to −4.5)
Abbreviations: CT, computed tomography; DXA, dual-energy x-ray absortiometry. *Sample sizes for ages 50 to 59 years, 60 to 69 years, and 70 to 75 years, respectively: exercisers = 47, 27, and 13; controls = 45, 29, and 12. †Body mass index is calculated as weight in kilograms divided by the square of height in meters. Sample sizes for body mass indexes of 24.1 to 27.5, 27.6 to 29.9, and 30.0 to 42.0,
respectively: exercisers = 24, 21, and 42; controls = 19, 26, and 41. 328 JAMA, January 15, 2003—Vol 289, No. 3 (Reprinted) 2003 American Medical Association. All rights reserved.
EXERCISE AND BODY FAT IN POSTMENOPAUSAL WOMEN
Figure 2. Percentage Change in Total Body
to sustain this loss over the long term.31
Fat at 12 Months by Tertile of Duration and
greater loss of intra-abdominal fat among
cise on intra-abdominal fat are needed.
vascular disease.21-25 Exercise may coun-
teract the aberrant metabolic profile as-
cise performed at the facility, which was
Body fat was measured by dual-energy x-ray absorp-
tiometry. Error bars indicate 95% confidence inter-
pared to make the necessary changes.
vals; duration, minutes per week spent in moderate-
intensity sports activity (low-active, Յ135 min/wk;intermediately active, 136-195 min/wk; and highly ac-
tive, Ͼ195 min/wk); change in fitness, low-active,
Յ5%; intermediately active, 5.1%-16%; and highlyactive, Ͼ16%; asterisk, significant difference com-
pared with controls (PϽ.05); and dagger, significant
difference compared with low-active group (PϽ.05). Figure 3. Percentage Change in
by Tertile of Duration and Changein Fitness Level
significantly greater weight and fat loss
trolled trial of a moderate-intensity exer-
Intra-abdominal body fat was measured by com-
puted tomography. Error bars indicate 95% confi-
dence intervals; duration, minutes per week spent in
moderate-intensity sports activity (low-active, Յ135min/wk; intermediately active, 136-195 min/wk; and
highly active, Ͼ195 min/wk); change in fitness, low-
active, Յ5%; intermediately active, 5.1%-16%; andhighly active, Ͼ16%; asterisk, significant difference
compared with controls (PϽ.05); and dagger, signifi-
cant difference compared with low-active group(PϽ.05).
of exercise is similar to current national
2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, January 15, 2003—Vol 289, No. 3 329
EXERCISE AND BODY FAT IN POSTMENOPAUSAL WOMEN
Critical revision of the manuscript for important in-tellectual content: Irwin, Yasui, Ulrich, Bowen, Rudolph,Schwartz, Yukawa, Aiello, Potter, McTiernan. Statistical expertise: Yasui. Obtained funding: Schwartz, McTiernan. Administrative, technical, or material support: Irwin,
cardiorespiratory fitness. High levels of
body fat, especially intra-abdominal fat.
Schwartz, Yukawa, Potter, McTiernan.
cardiorespiratory fitness reduce the rate
Study supervision: Irwin, Bowen, Rudolph, Schwartz,Potter, McTiernan. Author Contributions: Dr McTiernan, as principal Funding/Support: This study was supported by re-
investigator of this study, had full access to all of
search grant RO1-69334 from the National Cancer
the data in the study and takes responsibility for
Institute. Dr Irwin was also supported by a National
the integrity of the data and the accuracy of the data
Cancer Institute Cancer Prevention Training grant (T32
CA09661). A portion of this work was conducted
Study concept and design: Irwin, Yasui, Ulrich, Bowen,
through the University of Washington Clinical Re-
search Center Facility and was supported by National
Acquisition of data: Irwin, Ulrich, Rudolph, Schwartz,
Institutes of Health grants M01-RR-00037 and
of the exercise intervention lessened over
Analysis and interpretation of data: Irwin, Yasui, Ulrich,
Acknowledgment: We are indebted to the partici-
Bowen, Rudolph, Schwartz, Aeillo, Potter, McTiernan.
pants in the Physical Activity for Total Health Study
Drafting of the manuscript: Irwin, McTiernan. REFERENCES 1. Flegal KM, Carroll MD, Ogden CL, Johnson CL.
egories of glucose intolerance. Diabetes. 1979;28:
24. Van Pelt RE, Evans EM, Schechtman KB, Ehsani
Prevalence and trends in obesity among US adults,
AA, Korht WM. Contributions of total and regional
1999-2000. JAMA. 2002;288:1723-1727. 13. Patterson R, Kristal A, Tinker L, et al. Measure-
fat mass to risk for cardiovascular disease in women. 2. Pi-Sunyer FX. Health implications of obesity. Am J
ment characteristics of the Women’s Health Initia-
Am J Physiol Endocrinol Metab. 2002;282:E1023-
Clin Nutr. 1991;53(suppl 6):1595S-1603S.
tive food frequency questionnaire. Ann Epidemiol.3. Resnik H, Valsania P, Halter J, Lin X. Relation of 25. Kern P, Svoboda M, Eckel R, Van Wyk J. Insulin-
weight gain and weight loss on subsequent diabetes
14. Taylor H, Jacobs D, Shucker B, et al. A question-
like growth factor action and production in adipo-
risk in overweight adults. J Epidemiol Community
naire for the assessment of leisure-time physical ac-
cytes and endothelial cells from human adipose tis-
tivities. J Chronic Dis. 1978;31:741-755.
sue. Diabetes. 1989;38:710-717. 4. Field A, Coakley E, Must A, et al. Impact of over- 15. Pate R, Blair S, Durstine J, et al. Guidelines for 26. Perseghin G, Price T, Petersen K, et al. Increased
weight on the risk of developing common chronic dis-
Exercise Testing and Prescription. Philadelphia, Pa: Lea
glucose transport-phosporylation and muscle glyco-
eases during a 10-year period. Arch Intern Med. 2001;
gen synthesis after exercise training in insulin-
16. Borg GA. Psychophysical bases of perceived ex-
resistant subjects. N Engl J Med. 1996;335:1357-
5. Rexrode K, Hennekens C, Willett W, et al. A pro-
ertion. Med Sci Sports Exerc. 1982;14:377-387.
spective study of body mass index, weight change,
17. Ainsworth BE, Haskell WL, Whitt MC, et al. Com- 27. Keim N, Barbieri T, Van Loan M, et al. Energy ex-
and risk of stroke in women. JAMA. 1997;277:1539-
pendium of physical activities: an update of activity
penditure and physical performance in overweight
codes and MET intensities. Med Sci Sports Exerc. 2000;
women: response to training with and without ca-
6. Martinez ME, Giovannucci E, Spiegelman D, Hunter
loric restriction. Metabolism. 1990;39:651-657.
DJ, Willett WC, Colditz GA. Leisure-time physical ac-
18. Zeger SL, Liang KY. Longitudinal data analysis for 28. Dattilo A, Kris-Etherton P. Effects of weight re-
tivity, body size, and colon cancer in women. J Natl
discrete and continuous outcomes. Biometrics. 1986;
duction on blood lipids and lipoproteins: a meta-
Cancer Inst. 1997;89:948-955.
analysis. Am J Clin Nutr. 1992;56:320-328. 7. Huang Z, Hankinson S, Colditz G, et al. Dual ef- 19. Mourier A, Gautier J, De Kerviler E, et al. Mobi- 29. MacMahon S, Cutler J, Brittain E, Higgins M. Obe-
fects of weight and weight gain on breast cancer risk.
lization of visceral adipose tissue related to the im-
sity and hypertension: epidemiological and clinical is-
provement in insulin sensitivity in response to physi-
sues. Eur Heart J. 1987;8:57-70. 8. Pronk NP, Wing RR. Physical activity and long-
cal training in NIDDM: effects of branch-chain amino
30. Diabetes Prevention Program Research Group. Re-
term maintenance of weight loss. Obes Res. 1994;2:
acid supplements. Diabetes Care. 1997;20:385-391.
duction in the incidence of type 2 diabetes with life-
20. DiPietro L, Seeman T, Stachenfeld N, Katz L, Nadel
style intervention or metformin. N Engl J Med. 2002;
9. Asikainen T, Miilunpalo S, Oja P, Rinne M, Pas-
E. Moderate-intensity aerobic training improves glu-
anen M, Vuori I. Walking trials in postmenopausal
cose tolerance in aging independent of abdominal obe-
31. Jakicic J, Clark K, Coleman E, et al. Appropriate
women: effect of one vs two daily bouts on aerobic
sity. J Am Geriatr Soc. 1998;46:875-879.
intervention strategies for weight loss and preven-
fitness. Scand J Med Sci Sports. 2002;12:99-105. 21. Matsuzawa Y, Shimomura I, Nakamura T, et al.
tion of weight regain for adults: American College of
10. McTiernan A, Ulrich C, Yancey D, et al. The Physi-
Pathophysiology and pathogenesis of visceral fat obe-
Sports Medicine position stand. Med Sci Sports Ex-
cal Activity for Total Health (PATH) Study: rationale
sity. Obes Res. 1995;3(suppl 2):187S-194S.
and design. Med Sci Sports Exerc. 1999;31:1307-
22. Ross R, Fortier L, Hudson R. Separate associa- 32. US Department of Health and Human Services.
tions between visceral and subcutaneous adipose tis-
Physical Activity and Health: a Report of the Sur-11. Tworoger S, Yasui Y, Ulrich C, et al. Mailing strat-
sue distribution, insulin, and glucose levels in obese
geon General. Atlanta, Ga: Centers for Disease Con-
egies and recruitment into an intervention trial of the
women. Diabetes Care. 1996;19:1404-1411.
exercise effect on breast cancer biomarkers. Cancer23. Taniguchi A, Nakai Y, Sakai M, et al. Relation- 33. Blair S, Kampert J, Kohl H, et al. Influence of car- Epidemiol Biomarkers Prev. 2002;11:73-77.
ship of regional adiposity to insulin resistance and se-
diorespiratory fitness and other precursors on cardio-
12. National Diabetes Data Group. Classification
rum triglyceride levels in nonobese Japanese type 2
vascular disease and all-cause mortality in men and
and diagnosis of diabetes mellitus and other cat-
diabetic patients. Metabolism. 2002;51:544-548.
women. JAMA. 1996;276:205-210. 330 JAMA, January 15, 2003—Vol 289, No. 3 (Reprinted) 2003 American Medical Association. All rights reserved.
Sirolimus als De-Novo-Immunsuppressivum in Kombination mit Tacrolimus nach Herztransplantation M. Müller, B.M. Meiser, J. Groetzner, I. Kaczmarek, P. Landwehr, I. Adamidis P. Überfuhr, B. Reichart Herzchirurgische Klinik der Ludwigs-Maximilians-Universität München, Klinikum Großhadern Studiendesign Zielspiegel Dosierungsschema Monat 1-6 >6 Monate z Prospektive, of
Notes sur les technologies de la santé en émergence Le tiotropium : un substitut potentiel à l’ipratropium dans le traitement de la BPCO numéro 35 juillet 2002 Boehringer Ingelheim, Burlington (Ontario), le30 avril 2002) et à la Food and Drug Administration auxÉtats-Unis4, en quête de l’approbation de l’utilisation du9 Dans le traitement de la bronchopneumopathie médicam