Lifestyle,DM,CVD Risk Factors

8/12/2019 Lifestyle,DM,CVD Risk Factors

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n engl j med 351;26 w w w. ne jm . org d ec em be r 23, 2004 2683

The

new englandjournal of

medicine

established in 1812

december

23

, 2004

vol. 3 51 no. 26

Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 Yearsafter Bariatric Surgery

Lars Sjstrm, M.D., Ph.D., Anna-Karin Lindroos, Ph.D., Markku Peltonen, Ph.D., Jarl Torgerson, M.D., Ph.D.Claude Bouchard, Ph.D., Bjrn Carlsson, M.D., Ph.D., Sven Dahlgren, M.D., Ph.D., Bo Larsson, M.D., Ph.D.,Kristina Narbro, Ph.D., Carl David Sjstrm, M.D., Ph.D., Marianne Sullivan, Ph.D., and Hans Wedel, Ph.D.,

for the Swedish Obese Subjects Study Scientific Group*

abs t r ac t

From the Departments of Body Composi-tion and Metabolism (L.S., A.-K.L., B.C.,K.N., M.S.) and Anesthesiology (B.L.,C.D.S.), Sahlgrenska University Hospital,Gteborg, Nordic University of PublicHealth (H.W.), Gteborg; the Medical De-partment, Norra lvsborgs Lns Hospital,Trollhttan (J.T.); and Brjegatan 10B,Uppsala (S.D.) all in Sweden; the De-partment of Epidemiology and Health Pro-motion, National Public Health Institute,Helsinki, Finland (M.P.); and PenningtonBiomedical Research Center, Louisiana

State University, Baton Rouge (C.B.). Ad-dress reprint requests to Dr. Lars Sjstrmat SOS Secretariat, Sahlgrenska UniversityHospital, S-413 45 Gteborg, Sweden.

*The members of the Swedish Obese Sub-jects (SOS) Study Scientific Group are list-ed in the Appendix.

N Engl J Med 2004;351:2683-93.

Copyright 2004 Massachusetts Medical Society.

background

Weight loss is associated with short-term amelioration and prevention of metabolicand cardiovascular risk, but whether these benefits persist over time is unknown.

methods

The prospective, controlled Swedish Obese Subjects Study involved obese subjects whounderwent gastric surgery and contemporaneously matched, conventionally treatedobese control subjects. We now report follow-up data for subjects (mean age, 48 years;mean body-mass index, 41) who had been enrolled for at least 2 years (4047 subjects)or 10 years (1703 subjects) before the analysis (January 1, 2004). The follow-up rate forlaboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years.

results

After two years, the weight had increased by 0.1 percent in the control group and haddecreased by 23.4 percent in the surgery group (P


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besity is associated with in-

creased morbidity and mortality.

1

The in-creased morbidity is assumed to be me-

diated mainly by insulin resistance, diabetes,hypertension, and lipid disturbances conditionsthat affect one quarter of the North American pop-

ulation.

2,3

Over the short term (one to three years),lifestyle changes resulting in weight loss result inimprovements in insulin resistance,

4

diabetes,

5-7

hypertension,

8

and lipid disturbances

9-11

or in theprevention of these conditions. In contrast, several(but not all

12

) observational epidemiologic studieshave suggested that weight loss is associated withincreased overall mortality and mortality from car-diovascular causes, not only among thin

13

and nor-mal-weight

14

subjects, but also among obese subjects.

15-17

One overall aim of the Swedish Obese Subjects(SOS) Study was to address this apparent discrep-

ancy between the effects of weight loss on risk fac-tors and hard end points. In the current study, weassessed changes in cardiovascular risk factors overfollow-up periods of 2 and 10 years in surgically treated subjects and contemporaneously matched,conventionally treated control subjects. Changes inenergy intake and physical activity over the 10-yearperiod were also evaluated.

study design

The SOS Study was a prospective, nonrandomized,intervention trial involving 4047 obese subjects. Theoutcomes in a surgically treated group were com-pared with those in a contemporaneously matched,conventionally treated control group.

18 For the pur-poses of this report, all subjects who had been en-rolled at least 2 years (4047 subjects) or 10 years(1703 subjects) before the date of the analysis (Jan-uary 1, 2004) were included. The 4047 subjects wereall those who were finally enrolled in the SOS intervention study.

The seven ethics review boards involved in theSOS Study approved the protocol. Informed consent was obtained both from the subjects in the registry study and from those in the intervention study.

Registry Examination

As a result of recruitment campaigns through themass media and at 480 primary health care centersin Sweden, 11,453 subjects living in participating

counties (18 of the 24 counties in Sweden) sent stan-dardized application forms to the SOS secretariat between September 1987 and November 2000. All8966 applicants who fulfilled age and weight-for-height criteria were provided written informationabout the surgical and nonsurgical treatments of-

fered by the SOS Study. They also completed ques-tionnaires and were asked whether they wanted toparticipate as surgically treated or medically treatedsubjects. All 7593 subjects who returned their ques-tionnaires were offered participation in the registry examination, and 6905 completed that examina-tion. According to individual treatment preferencesand data obtained from the registry examination,eligible subjects were assigned either to the surgery group of the intervention study or to a pool of poten-tial control subjects.

Surgical Visit

The eligibility of candidates for surgery was deter-mined by computer, and the result was manually checked by the examining surgeon. If a candidate was eligible, an operation was scheduled. On aver-age, the surgical visit occurred eight months afterthe registry examination and five months before theoperation itself, which marked the start of the intervention study. Eight weeks before a subject underwent surgery, an optimal matched control was se-lected, on the basis of variables described below,from among the subjects in the pool of potentialcontrols. Thus, matching was contemporaneousand was based on registry data, both for the surgi-cally treated subjects and for the control subjects.

Inclusion Examination

The inclusion examination for subjects for whomsurgery was planned and for their matched controls was undertaken 4 weeks before surgery (i.e., 4 weeksbefore the start of the intervention study), on aver-age 13 months after the registry examination. Thisdelay was a consequence of the waiting time for sur-gery at the 25 participating surgical departments.The controls underwent their manual eligibility check at the time of the inclusion examination.

Intervention Study

The intervention study for a surgically treated subject and his or her matched control began on the day of the surgically treated subjects operation. Thedates of all subsequent examinations (at 0.5, 1.0,2.0, 3.0, 4.0, 6.0, 8.0, and 10.0 years) for both sub-

o

m e t h o d s

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long-term weight loss and changes in cardiovascular risk factors

2685

jects were calculated in relation to the date of sur-gery. Inclusion criteria for the intervention study were a body-mass index (calculated as the weight in kilograms divided by the square of the height inmeters) of 34 or more (for men) or 38 or more (for women) and an age of 37 to 60 years. Exclusion cri-

teria, described elsewhere,

18

were minimal and were aimed at ensuring that the subjects in the sur-gery group could tolerate the operation. Identicalinclusion and exclusion criteria were used in the twostudy groups. Subjects with diabetes, hypertension,or lipid disturbances were not excluded, nor weresubjects who had had a myocardial infarction or astroke more than six months before inclusion.

Matching

The SOS Study was not randomized; rather, subjects were matched according to the method of se-quential treatment assignment,

19

with balancing

of confounding factors measured at baseline in pro-spective, nonrandomized intervention trials. Thefollowing 18 matching variables were considered

18

:sex, age, weight, height, waist and hip circumfer-ences, systolic blood pressure, serum cholesteroland triglyceride levels, smoking status, diabetes,menopausal status, four psychosocial variables withdocumented associations with the risk of death, andtwo personality traits related to treatment preferenc-es. The investigators had no influence on the com-puterized matching process.

Clinical and Biochemical Assessments

At each visit, measurements of weight, height, waist circumference, and blood pressure were obtained.In addition, energy intake (in kilocalories per day) was estimated with use of the validated SOS Dietary Questionnaire.

20,21

Subjects were also asked to ratetheir physical activity during leisure and work timeon a scale from 1 to 4, in which 1 denotes sedentary activity and 4 regular strenuous exercise.

20,22

In thecurrent report, ratings were dichotomized; a ratingof 1 corresponded to physically inactive and ratingsof 2, 3, or 4 to physically active.

Biochemical variables were measured at the reg-istry examination, at the inclusion examination(year 0 of the intervention study), and at years 2 and10 of the intervention study (Table 1). All bloodsamples, which were obtained in the morning aftera 10-to-12-hour fast, were analyzed at the CentralLaboratory of Sahlgrenska University Hospital (ac-credited according to European Norm EN45001).

The schedule, questionnaires, blood pressure andanthropometric measurements, and laboratory ex-aminations were identical for surgically treated subjects and their matched controls.

treatments

The surgically treated subjects underwent fixed or variable banding, vertical banded gastroplasty, orgastric bypass.

23

The contemporaneously matchedcontrols received the nonsurgical treatment for obe-sity that was customary for the center at which they were registered. No attempt was made to standard-ize the nonsurgical treatment, which ranged fromsophisticated lifestyle intervention and behaviormodification to, in some practices, no treatment whatsoever. No antiobesity drugs were approved inSweden until 1998.

criteria for health and disease

Criteria for health and disease were based on cutoff values or the use of medication for the condition inquestion, according to principles specified elsewhere.

11

However, in the course of the study, thecriterion for diagnosing diabetes decreased to a fast-ing blood glucose level of 110 mg per deciliter (6.1mmol per liter) or greater, corresponding to a fast-ing plasma glucose level of 126 mg per deciliter(7.0 mmol per liter) or greater, in accordance withthe new criteria of the American Diabetes Associa-tion.

24

Similarly, the criterion for diagnosing hy-pertension decreased to a systolic pressure of 140mm Hg or greater or a diastolic pressure of 90mm Hg or greater.

25

Other criteria included thefollowing: hypercholesterolemia (cholesterol level,201 mg per deciliter [5.2 mmol per liter] or great-er

26

); hypertriglyceridemia (triglyceride level, 150mg per deciliter [1.7 mmol per liter] or greater

26

);a low level of high-density-lipoprotein (HDL) cho-lesterol (less than 39 mg per deciliter [1.0 mmolper liter]

26

); and hyperuricemia (uric acid level, 7.6mg per deciliter [450 mol per liter] or greater inmen and 5.7 mg per deciliter [340 mol per liter] orgreater in women).

outcome variables

The primary outcome variable in the SOS Study as a whole was overall mortality. Three secondary out-come variables are described in this report. The first was the difference between the surgery group andthe control group with respect to changes in body weight, risk factors, energy intake, and the propor-



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tion of subjects who were physically active. Thesecalculations included all the subjects and did not take medication use or baseline disease into ac-count. The next secondary outcome was the dif-ference between the two groups in the incidence of risk conditions over 2- and 10-year periods amongthe subjects unaffected by those risk conditions at baseline (i.e., the primary preventive effect of weight loss). The final secondary outcome was the differ-

ence between the two groups in the rate of recovery from risk conditions over 2- and 10-year periodsamong those who had been affected by those con-ditions at baseline.

statistical analysis

The intervention study had 80 percent power (at an alpha level of 0.05) to detect a difference in totalmortality between a group of 2000 surgically treat-

* Plusminus values are means SD. To convert the values for glucose to milligrams per deciliter, divide by 0.05551. To convert the values forinsulin to picomoles per liter, multiply by 7.175. To convert the values for uric acid to milligrams per deciliter, divide by 59.48. To convert thevalues for triglycerides to milligrams per deciliter, divide by 0.01129. To convert the values for cholesterol to milligrams per deciliter, divideby 0.02586. HDL denotes high-density lipoprotein.

Among the subjects who did not complete 10 years of the study, the controls were older and had higher systolic blood pressure than the sur-gically treated subjects, whereas the surgically treated subjects were heavier and had a larger waist circumference (P values not shown).

P values are for the comparison with data for subjects in the control group under the indicated conditions. P values are for the comparison with matching data for subjects in the control group who completed the 10-year examination. P values are for the comparison with matching data for subjects in the surgically treated group who completed the 10-year examination. P


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ed subjects and a group of 2000 controls followedfor 10 years.

18

To evaluate the originally chosentreatment strategy according to pragmatic clinical-treatment principles,

27

subjects in the surgery group who completed 10 years of the study and who un-derwent reoperation (band removal in 15 subjects

and conversion to another type of surgical treatment in 62) or who had a spontaneous band disruption(in 2 subjects) were considered surgically treatedand remained in their original treatment subgroup.Similarly, control subjects who later underwent bar-iatric surgery (34 subjects) were considered controlsthroughout the study. All analyses presented hereare based on data from subjects who completed 2 or10 years of the study. However, for confirmatory rea-sons, additional calculations were performed by re-placing all missing data with baseline data, accord-ing to the baseline observation carried forwardmethod.

28

Mean values and standard deviations are used todescribe the baseline characteristics of the two treat-ment groups. Analysis of covariance was used to test for differences in changes in risk factors betweenthe two treatment groups. Treatment group was in-cluded as a covariate, as were sex, age, body-massindex, and the baseline level of each studied varia-ble. Adjusted differences, with 95 percent confi-dence intervals, are reported. Logistic regression was used to compare the incidence of disease andrates of recovery. The data were adjusted for sex,age, and body-mass index at baseline, and the re-sulting differences in risk are reported as odds ra-tios with 95 percent confidence intervals. All report-ed P values are two-sided. Statistical analyses werecarried out with use of the Stata statistical package(version 7.0).

29

subjects

At least 10 years before the date of the current analy-sis, 851 surgically treated subjects had been enrolledin the SOS Study. The surgically treated subjects hadbeen contemporaneously matched with 852 obesecontrol subjects. The matching resulted in twogroups that were not significantly different with re-spect to sex distribution, height, blood pressure,blood glucose level, serum lipid levels, or serum uricacid level (data not shown). At the time of matching,the surgically treated subjects were slightly young-er than the control subjects (46.1 vs. 47.4 years of

age, P=0.005), were heavier (119.2 vs. 116.1 kg,P


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gastroplasty (Fig. 1). The fractions of subjects who,after completing 10 years of the study, had a loss of less than 5 percent of their initial weight were 72.7percent (control group), 8.8 percent (gastric-bypasssubgroup), 13.8 percent (vertical-banded-gastro-plasty subgroup), and 25.0 percent (banding sub-group). The fractions of subjects achieving 20 per-cent weight loss or more over the 10-year period were 3.8 percent (control group), 73.5 percent (gas-tric-bypass subgroup), 35.2 percent (vertical-band-ed-gastroplasty subgroup), and 27.6 percent (band-ing subgroup).

lifestyle changes

Mean energy intake at the time of inclusion in theintervention study was 2882 kcal per day among thesurgically treated subjects, as compared with 2526kcal per day among the controls. As Figure 2 andTable 2 indicate, the baseline adjusted energy intake was significantly lower in the surgery group than inthe control group over the 10-year period. Similar-ly, the fraction of subjects physically active during

leisure time was higher in the surgery group overthe 10-year period, and the fraction of those physi-cally active during work time was higher in the sur-gery group for the first 6 years of the intervention.

effects on anthropometric variablesand mean risk-factor values

Table 2 shows the changes in risk factors for allavailable subjects, independent of baseline statusand medication use. The waist circumference wasreduced more in the surgery group than in the con-trol group after 2 and 10 years. Glucose and insulinlevels increased in the control group, whereas sub-stantial decreases were seen in the surgically treat-ed group after both 2 and 10 years of observation.Similarly, changes in uric acid, triglyceride, andHDL cholesterol levels were more favorable in thesurgically treated group than in the control groupafter 2 and 10 years. Systolic blood pressure was re-duced by more in the surgery group at two yearsonly. Diastolic blood pressure and total cholesterol were reduced by more in the surgery group than in

Figure 1. Weight Changes among Subjects in the SOS Study over a 10-Year Period.

All data are for subjects who completed 10 years of the study. The average weight change in the entire group of surgicallytreated subjects was almost identical to that in the subgroup of subjects who underwent vertical banded gastroplasty.TheI

bars represent the 95 percent confidence intervals.

5

W e i g h

t C h a n g e

( % )

5

0

10

15

25

30

40

20

35

450.0 1.00.5 2.0 3.0 4.0 6.0 8.0 10.0

Control

Banding

Vertical bandedgastroplasty

Gastricbypass

Years of Follow-up

No. of SubjectsControlBandingVertical banded gastroplastyGastric bypass

62715645134

53514440129

54214741232

56315041732

57714942933

58715343834

58515043834

59415443834

62715645134



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* D a t a a r e

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l s u b

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( 9 5 % C I )

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t r o l

G r o u p

( N =

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( N =

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d i n g

( N = 1

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t r o p

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( N = 4

5 1 )

G a s

t r i c B y p a s s

( N = 3

4 )

p e r c e n t

p e r c e n t

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the control group after 2 years but less reduced af-ter 10 years. The pulse-pressure increase was less

pronounced in the surgery group than in the con-trol group after 10 years (Table 2).

The 10-year changes in weight, body-mass in-dex, and waist circumference were larger for subjects who underwent vertical banded gastroplasty and gastric bypass than for those who underwent banding. Insulin, triglyceride, HDL cholesterol, andtotal cholesterol levels were more improved amongthe subjects who underwent gastric bypass thanamong those who underwent banding (Table 2).

effects on incidence of and recoveryfrom risk conditions

As Figure 3 shows, the incidence rates of hyper-triglyceridemia, diabetes, and hyperuricemia weremarkedly lower in the surgically treated group thanin the control group after 2 and 10 years. The inci-dence of low HDL cholesterol was significantly low-er in the surgical group after 2 years but not after 10 years. The incidence of hypertension and hyper-cholesterolemia did not differ between the groupsover the 2- and 10-year periods (Fig. 3).

Recovery from hypertension, diabetes, hyper-triglyceridemia, a low HDL cholesterol level, and hy-peruricemia was more frequent in the surgical group

than in the control group, both at 2 and 10 years(Fig. 4). The rates of recovery from hypercholester-olemia did not differ between the two groups aftereither 2 or 10 years.

E n e r g y

I n t a k e ( k c a

l / d a y )

0 1.00.5 2.0 3.0 4.0 6.0 8.0 10.0

Years of Follow-up

0 1.00.5 2.0 3.0 4.0 6.0 8.0 10.0Years of Follow-up

0 1.00.5 2.0 3.0 4.0 6.0 8.0 10.0

Years of Follow-up

Control

Surgery

P r o p o r

t i o n

A c t

i v e

d u r i n g

L e i s u r e

T i m e

( % )

Control

Surgery

P r o p o r

t i o n

A c t

i v e a t

W o r

k ( % )

20

0

40

80

60

100

20

0

40

80

60

100

500

0

1000

2500

2000

1500

3000

Control

Surgery

A

B

C

** * * ** * **

** * * ** * *

* *

Figure 2. Lifestyle Changes among the Subjectsin the SOS Study over a 10-Year Period.

Mean energy intake (in kilocalories per day) (Panel A)and the percentage of subjects who were physically ac-tive during leisure time and at work (Panels B and C, re-spectively) are shown. Energy intake and the proportionof active subjects at baseline (year 0) are unadjustedvalues, whereas the values during the follow-up havebeen adjusted for sex, age, body-mass index, and energyintake or physical activity at baseline. All data are fromsubjects who completed 10 years of the study. The num-bers of subjects at each time point are the same as thoseshown in Figure 1. Asterisks denote P


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baseline observations carried forward

In additional calculations, all missing observations were replaced by baseline observations. The conclu-sions with respect to mean risk-factor values, inci-dence rates, and rates of recovery for subjects whocompleted the study remained the same in the analy-

sis in which baseline observations were carried forward (data not shown).

death and other adverse events

Five of the 2010 subjects who underwent surgery (0.25 percent) died postoperatively. As reportedelsewhere for 1164 patients,

23

151 (13.0 percent)had 193 postoperative complications (bleeding in0.5 percent, embolism or thrombosis in 0.8 per-cent, wound complications in 1.8 percent, deep in-fections [leakage or abscess] in 2.1 percent, pul-monary complications in 6.1 percent, and othercomplications in 4.8 percent). In 26 patients (2.2

percent), the postoperative complications were se-rious enough to require reoperation. The study isongoing with respect to analyses of mortality andthe incidence of myocardial infarction, stroke, andcancer. The safety monitoring committee found noreason to interrupt the study prematurely becauseof positive effects or harm.

The surgically treated subjects in this study hadgreater weight loss, more physical activity, and low-er energy intake than the control subjects over a 10- year period. Furthermore, the 2- and 10-year ratesof recovery from all the studied risk factors, except hypercholesterolemia, were more favorable in thesurgery group than in the control group, as werethe 2- and 10-year incidence rates of hypertriglycer-idemia, diabetes, and hyperuricemia. All reportedresults are based on subjects who completed 2 or10 years of the study. However, the conclusions re-mained the same when data from all included subjects were used and missing follow-up data werereplaced by baseline data, according to the conser- vative baseline observation carried forward pro-cedure.

28

The mean changes in weight and risk factors were more favorable among the subjects treated by gastric bypass than among those treated by band-ing or vertical banded gastroplasty. The low num-ber of subjects who were followed for 10 years after

gastric bypass prohibited incidence and recovery calculations, but the technique appears to be a cur-rent method of choice. The large weight loss aftergastric bypass, as compared with that after the oth-er types of surgery, may be related to altered gut-to-brain signaling.

30,31

Most intervention studies with one to three yearsof follow-up are in agreement with our two-year ob-

d i s c u s s i o n

Figure 3. Incidence of Diabetes, Lipid Disturbances, Hypertension, and Hy-peruricemia among Subjects in the SOS Study over 2- and 10-Year Periods.

Data are for subjects who completed 2 years and 10 years of the study. Thebars and the values above the bars indicate unadjusted incidence rates;I

barsrepresent the corresponding 95 percent confidence intervals (CIs). The oddsratios, 95 percent CIs for the odds ratios, and P values have been adjusted forsex, age, and body-mass index at the time of inclusion in the intervention study.

60

I n c i

d e n c e

( % o f s u

b j e c

t s )

40

30

10

50

20

0

Hypertriglyceridemia Low HDL Cholesterol Hypercholesterolemia

No. of subjectsControlSurgery

Odds ratio95% CIP value

2 Yr 10 Yr

1881351.16

0.691.950.57

5965041.27

0.951.690.11

2 Yr 10 Yr

4404310.57

0.291.150.12

117412930.21

0.140.32


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servations concerning the effects of weight loss onblood pressure,

8,32,33

lipids,

9,34,35

uric acid,

36

anddiabetes.

5-7

In contrast, to our knowledge there havebeen no controlled, prospective intervention trialsagainst which our long-term results can be com-pared. In a retrospective, nine-year analysis, gastric

bypass surgery was found to have a dramatic effect on the incidence of type 2 diabetes and overall mor-tality.

37

Sixteen-year observational data on weight loss from the Framingham Study

38

are in agreement with the primary preventive effect on diabetes that we found over a 10-year period. In contrast, observa-tional, epidemiologic 12-to-15-year data on weight loss indicated a primary preventive effect on hyper-tension in the Nurses Health Study,

39

but this find-ing could not be confirmed in our controlled 10-yearintervention. Our results indicate that the long-termeffects (effects at 10 years) of maintained weight loss on risk factors cannot always be estimated from

short-term observations (up to 2 years).The main limitation of the SOS Study is that it

was not randomized. When it was approved as amatched, prospective intervention study in 1987, sixof the seven involved ethics review boards in Swe-den considered the high mortality rate after gastricsurgery for obesity (1 to 5 percent in the 1970s and1980s

40

) unacceptable for randomization.In summary, this study indicates that bariatric

surgery is a favorable option in the treatment of se- vere obesity. That not all obesity-associated risk fac-tors were improved by sustained weight loss under-scores the importance of obtaining long-term dataconcerning the effect of weight loss on overall mor-tality and on the incidence rates of myocardial in-farction, stroke, and cancer.

Supported by a grant (05239) from the Swedish Medical ResearchCouncil and by grants from HoffmannLa Roche, Basel, Switzer-land (to Dr. Sjstrm), and Bristol-Myers Squibb (to Dr. Bouchard).

Dr. Carlsson reports holding equity in AstraZeneca.We are indebted to the staff members at the 480 primary health

care centers and 25 surgical departments that participated in thestudy.

append ix

The SOS Study Scientific Group consists of L. Sjstrm (chair), L. Backman, C. Bengtsson, C. Bouchard, B. Carlsson, L. Carlsson, S. Dahl-gren, P. Jacobsson, E. Jonsson, K. Karason, J. Karlsson, B. Larsson, A.-K. Lindroos, L. Lnn, H. Lnnroth, K. Narbro, I. Nslund, M. Pel-tonen, A. Rydn, C.D. Sjstrm, K. Stenlf, M. Sullivan, C. Taft, J. Torgerson, and H. Wedel.

r e f e r ences

1.

Sjstrm LV. Mortality of severely obesesubjects. Am J Clin Nutr 1992;55:Suppl:516S-523S.

2.

Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obe-sity-related health risk factors, 2001. JAMA2003;289:76-9.

3.

Ford ES, Giles WH, Dietz WH. Preva-lence of the metabolic syndrome among USadults: findings from the Third NationalHealth and Nutrition Examination Survey. JAMA 2002;287:356-9.

4.

Bjrntorp P, De Jounge K, Sjstrm L,Sullivan L. The effect of physical training on

insulin production in obesity. Metabolism1970;19:631-8.

5.

Knowler WC, Barrett-Connor E, FowlerSE, et al. Reduction in the incidence of type 2diabetes with lifestyle intervention or met-formin. N Engl J Med 2002;346:393-403.

6.

Tuomilehto J, Lindstrm J, Eriksson JG,

Figure 4. Recovery from Diabetes, Lipid Disturbances, Hypertension,and Hyperuricemia over 2 and 10 Years in Surgically Treated Subjectsand Their Obese Controls.

Data are for subjects who completed 2 years and 10 years of the study. Thebars and the values above the bars indicate unadjusted rates of recovery;I barsrepresent the corresponding 95 percent confidence intervals (CIs). The oddsratios, 95 percent CIs for the odds ratios, and P values have been adjusted forsex, age, and body-mass index at the time of inclusion in the intervention study.

100

R a t e o f

R e c o v e r y

( % o f s u

b j e c

t s )

60

40

80

20

0

No. of subjectsControlSurgery

Odds ratio95% CIP value

2 yr 10 yr

4354981.30

0.921.830.14

104813271.22

0.981.510.07

2 yr 10 yr

1661692.35

1.443.840.001

3964455.28

3.857.23


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