ORIGINAL ARTICLE
EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME
Effect of Bariatric Surgery on the Metabolic Syndrome:
A Population-Based, Long-term Controlled Study
JOHN A. BATSIS, MBBCH; ABEL ROMERO-CORRAL, MD, MSC; MARIA L. COLLAZO-CLAVELL, MD;
MICHAEL G. SARR, MD; VIREND K. SOMERS, MD, PHD; AND FRANCISCO LOPEZ-JIMENEZ, MD, MSC
OBJECTIVE: To assess the effect of weight loss by bariatric surgery
on the prevalence of the metabolic syndrome (MetS) and to
examine predictors of MetS resolution.
PATIENTS AND METHODS: We performed a population-based, retro-
spective study of patients evaluated for bariatric surgery between
January 1, 1990, and December 31, 2003, who had MetS as
defined by the American Heart Association/National Heart, Lung,
and Blood Institute (increased triglycerides, low high-density lipo-
protein, increased blood pressure, increased fasting glucose, and
a measure of obesity). Of these patients, 180 underwent Roux-en-
Y gastric bypass, and 157 were assessed in a weight-reduction
program but did not undergo surgery. We determined the change
in MetS prevalence and used logistic regression models to deter-
mine predictors of MetS resolution. Mean follow-up was 3.4
years.
RESULTS: In the surgical group, all MetS components improved,
and medication use decreased. Nonsurgical patients showed im-
provements in high-density lipoprotein cholesterol levels. After
bariatric surgery, the number of patients with MetS decreased
from 156 (87%) of 180 patients to 53 (29%); of the 157 nonsurgi-
cal patients, MetS prevalence decreased from 133 patients (85%)
to 117 (75%). A relative risk reduction of 0.59 (95% confidence
interval [CI], 0.48-0.67; P<.001) was observed in patients who
underwent bariatric surgery and had MetS at follow-up. The num-
ber needed to treat with surgery to resolve 1 case of MetS was
2.1. Results were similar after excluding patients with diabetes or
cardiovascular disease or after using diagnostic criteria other
than body mass index for MetS. Significant predictors of MetS
resolution included a 5% loss in excess weight (odds ratio, 1.26;
95% CI, 1.19-1.34; P<.001) and diabetes mellitus (odds ratio,
0.32; 95% CI, 0.15-0.68; P=.003).
CONCLUSION: Roux-en-Y gastric bypass induces considerable and
persistent improvement in MetS prevalence. Our results suggest
that reversibility of MetS depends more on the amount of excess
weight lost than on other parameters.
Mayo Clin Proc. 2008;83(8):897-906
ACEI = angiotensin-converting enzyme inhibitor; AHA = American Heart
Association; ARB = angiotensin receptor blocker; ATP = Adult Treat-
ment Panel; BMI = body mass index; CI = confidence interval; CV =
cardiovascular; HDL-C = high-density lipoprotein cholesterol; MetS =
metabolic syndrome; NHLBI = National Heart, Lung, and Blood Insti-
tute; RYGB = Roux-en-Y gastric bypass; TG = triglyceride
T he components of the metabolic syndrome (MetS) ac-
count for a substantial portion of the attributable risk
of atherosclerotic cardiovascular (CV) diseases. All 5 com-
ponents of the American Heart Association (AHA)/Na-
tional Heart, Lung, and Blood Institute (NHLBI) definition
of MetS have been linked independently to CV diseases,
Mayo Clin Proc. • August 2008;83(8):897-906
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including increased levels of serum triglycerides (TGs),
low levels of serum high-density lipoprotein cholesterol
(HDL-C), elevated blood pressure, increased fasting
plasma glucose levels, and an increased waist circumfer-
ence.1 With the increasing prevalence of MetS and its
strong association with the development of diabetes melli-
tus and CV disease, this syndrome is an important public
health concern.2-4
Substantial evidence suggests that insulin resistance is
the underlying abnormality in the pathophysiology of
MetS5 and that lifestyle modifications are the cornerstone
of management.6,7 Increased physical activity and a healthy
diet for people with impaired fasting blood glucose re-
duces the incidence of type 2 diabetes mellitus,8 even
when weight loss is only modest (<10% of total body
weight).9 Because most dietary interventions do not
achieve more than a 10% weight loss and most lost weight
is regained, the net effect of considerable and long-lasting
weight loss on MetS is unknown.
Bariatric surgery, an approved treatment of obesity
when other measures have failed,10 induces long-standing,
profound weight loss.11 Most patients eligible for weight
reduction by bariatric procedures have a substantial num-
ber of components of MetS; most of their weight loss can
be attributed to reduced caloric intake and, to some extent,
partial malabsorption of nutrients or bypass of the duode-
num by Roux-en-Y gastric bypass (RYGB). This patient
population presents a unique opportunity to determine the
effect of major weight loss on MetS prevalence without the
From the Division of Primary Care Internal Medicine (J.A.B.), Division of
Cardiovascular Diseases (A.R.-C., V.K.S., F.L.-J.), Division of Endocrinology,
Diabetes, Metabolism and Nutrition (M.L.C.-C.), and Department of Surgery
(M.G.S.), Mayo Clinic, Rochester, MN.
Dr Romero-Corral is supported by a postdoctoral fellowship from the American
Heart Association. Dr Somers is supported by grants from the National
Institutes of Health (HL-65176, HL-70302, HL-73211, and M01-RR00585).
Dr Lopez-Jimenez is a recipient of a Clinical Scientist Development Award from
the American Heart Association.
Presented in part at the 68th Annual Scientific Session of the American
Diabetes Association, San Francisco, CA, June 6-10, 2008 (Abstract #1747-P).
Individual reprints of this article are not available. Address correspondence to
Francisco Lopez-Jimenez, MD, MSc, Division of Cardiovascular Diseases,
Mayo Clinic, 200 First St SW, Rochester, MN 55905 (lopez@mayo.edu).
© 2008 Mayo Foundation for Medical Education and Research
• www.mayoclinicproceedings.com 897
EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME
confounding factor of increased (moderate to intense)
physical activity. We evaluated the effect of bariatric sur-
gery on the prevalence of MetS in a population-based
cohort of patients with morbid class II to III obesity and a
body mass index (BMI) (calculated as weight in kilograms
divided by height in meters squared) of 35 or higher by
comparing the prevalence of MetS in patients who under-
went RYGB and in nonsurgical patients.
PATIENTS AND METHODS
We performed a population-based, retrospective cohort
study of all Olmsted County, Minnesota, patients referred
for bariatric surgery at Mayo Clinic’s site in Rochester,
MN, between January 1, 1990, and December 31, 2003.
Patients were identified using a centralized diagnostic in-
dex and the Rochester Epidemiology Project. All bariatric
interventions in the county are performed at our institution.
The Rochester Epidemiology Project is a comprehensive
record-linkage system that has been funded continually by
the Federal government since 1966 for use in disease-
related epidemiology.12 Olmsted County patients have all
their medical care indexed, allowing complete ascertain-
ment of patients’ medical histories. The county is a rela-
tively isolated and self-contained area. Medical care is
provided predominantly by Mayo Clinic and its hospitals
and by Olmsted Medical Center and its hospital. Health
care delivery by a limited number of private practitioners is
also captured. This study was approved by the institutional
review boards of Mayo Clinic and the Olmsted Medical
Center.
Patients’ primary place of residence was determined
using baseline demographic information, and county resi-
dence was verified using US Postal Service zip codes. The
surgical cohort was identified using the Mayo Surgical
Index, with weight reduction using RYGB as the primary
indication. Of the 231 Olmsted County residents who had
undergone RYGB, 16 patients were excluded because they
had a BMI less than 35, and 35 patients because they had
incomplete data or a follow-up of fewer than 3 months,
yielding a surgical cohort of 180 patients.
Our comparison group included patients who were
evaluated for bariatric surgery at the multidisciplinary
Mayo Clinic Nutrition Center but who did not undergo
surgery because they voluntarily declined it, were ineli-
gible due to denial by insurance providers, or did not
maintain lifestyle interventions during their evaluation. A
minority were excluded for psychiatric reasons. As is often
the case in clinical practice, patient exclusion from bariatric
interventions was multifactorial. Of the 252 Olmsted
County patients who were identified, 19 were excluded
because they had a BMI less than 35 (most of whom under-
898 Mayo Clin Proc. • August 2008;83(8):897-906
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
went revisional bariatric operative procedures for complica-
tions) and 76 because they had no further medical follow-up
or had a follow-up of less than 3 months. Our final compari-
son cohort consisted of 157 patients. Both surgical and
nonsurgical patients received medical and dietetic care as
well as extensive counseling about the importance of physi-
cal activity.
Time of bariatric surgery and time of nutrition consulta-
tion were considered the baseline time for the surgical and
nonsurgical groups, respectively. We defined our baseline
variables on the basis of information present in the medical
record from the baseline time or earlier; follow-up vari-
ables were based on information at time of last follow-up
evaluation. Because major weight loss or substantial meta-
bolic changes do not typically occur before 3 months, all
patients in our study had a minimum follow-up of at least 3
months. Height and weight were measured in a standard-
ized manner by a trained nurse. We used the method of
Robinson et al13 to calculate ideal body weight.
We diagnosed MetS using the 5 components described
by AHA/NHLBI in 20051: increased serum TG levels, low
serum HDL-C levels, increased blood pressure, increased
fasting plasma glucose, and increased waist circumference.
Because waist circumference was not documented rou-
tinely in the medical record, we used BMI as a surrogate for
central obesity; data have shown that most patients with a
BMI of 30 or higher have a large waist circumference.14
Patients who were taking fibrates or nicotinic acid or
whose serum TG levels were 150 mg/dL or higher were
classified as having hypertriglyceridemia. Serum HDL-C
levels were considered low if they were less than 40 mg/dL
in male patients and less than 50 mg/dL in female patients
or in patients treated with nicotinic acid or fibrates specifi-
cally for this disorder. We classified patients as having
hypertension if their blood pressure was higher than 135/85
mm Hg, or if they were taking any medications specifically
for hypertension, including β-blockers, calcium channel
blockers, angiotensin-converting enzyme inhibitors (ACEIs),
angiotensin receptor blockers (ARBs), thiazides, or loop or
potassium-sparing diuretics. These medications were in-
cluded only if the patient had a coexisting documented
diagnosis of hypertension. Increased fasting plasma glu-
cose concentration was defined as greater than 100 mg/dL
without the diagnosis of diabetes mellitus. Patients were
considered to have diabetes mellitus if their fasting glucose
was 126 mg/dL or higher or if they were taking insulin or
oral hypoglycemic agents. A diagnosis of MetS required 3
or more criteria. Finally, we determined the effect on the
prevalence of MetS, defined as 2 or more components
without obesity as a diagnostic criterion. In a subanalysis of
surgical patients with a baseline diagnosis of MetS and
more than 1 year of follow-up, patients were classified as
• www.mayoclinicproceedings.com

MetS responders if they no longer fulfilled criteria for MetS
at their most recent evaluation and as nonresponders if they
continued to have 3 or more criteria of MetS at follow-up.
STATISTICAL ANALYSES
Continuous data are presented as mean ± SD and categori-
cal data as number and percentage. Within-group compari-
sons between baseline and follow-up were compared using
a 2-sided, paired t test and Wilcoxon signed rank test for
continuous variables and a McNemar test for categorical
variables. Intergroup comparisons between surgical and
nonsurgical patients at baseline and changes between
groups were compared using a 2-sample t test of unequal
variances, a Wilcoxon rank sum test, a χ2 test, or a Fisher
exact test, depending on the type of data. For changes in
categorical variables between groups, we compared the 3-
point scale distributions (improved, no change, worsened)
and applied the Cochran-Armitage trend test. We applied
logarithmic transformation because of the skewness of tri-
glyceride values.
We sought to determine whether the amount of weight
loss, defined as the percent of excess weight lost, was the
main predictor of MetS resolution. We constructed mul-
tiple logistic regression models using backward selection
to identify predictors of MetS resolution at follow-up in
patients with MetS at baseline. Our inclusion threshold was
P<.25, and the exclusion threshold for variables was P=.10.
Initially, we excluded patients with a follow-up of less than
1 year because previous studies have suggested that weight
loss is not linear during this period11 and normally plateaus
after 1 year. The overall cohort of patients with MetS at
baseline was stratified by quartiles according to their fol-
low-up time. Because of the limited number of events in
each group, we adjusted only for age and sex in these
multivariate analyses.
Models were created to test whether our primary predic-
tor, percentage of excess weight lost, was significantly
different in these groups. We determined whether the
within-quartile β coefficients differed within each cohort to
further elicit the effect of follow-up time. Because no dif-
ferences were observed, we analyzed the entire cohort of
MetS patients at baseline with a follow-up greater than 1
year. Univariate predictors were then entered into a multi-
variate model, with the exception of any measures related to
weight or glucose, because of colinearity with percentage of
excess weight lost and diabetes, both predictors of interest.
The first model (Model 1) defined MetS as 3 or more
components. Because patients who undergo bariatric sur-
gery lose weight and may be cured of their obesity, the
likelihood for MetS response is higher in these patients.
Therefore, to have a MetS definition independent of BMI,
we developed a second model (Model 2) defining MetS as
Mayo Clin Proc. • August 2008;83(8):897-906
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EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME
2 or more components and excluding obesity as a diagnos-
tic criterion. This second model allowed us to determine
the potential role of percentage of excess weight lost on the
resolution of other components of MetS. We examined all
patients who had MetS at baseline, regardless of whether
they had undergone surgery; both models included
covariates, such as age, sex, baseline TG levels, presence of
diabetes at baseline, use of an ACEI or ARB, and percent-
age of excess weight lost. We separately adjusted for fol-
low-up time as an additional covariate in a multiple logistic
regression analysis for MetS, defined as 3 or more compo-
nents (Model 1A), and MetS, defined as 2 or more compo-
nents (Model 1B), to ascertain whether this variable altered
our results.
We tested Model 1 solely on patients with baseline
MetS (≥3 components) who underwent bariatric surgery
and were followed up for more than 1 year to determine
possible associations with MetS resolution. The same
covariates as in the aforementioned models were included,
in addition to HDL-C levels. In the nonsurgical group, we
independently assessed percentage of excess weight lost as
a predictor in Models 1 and 2 and incorporated follow-up
time in Models 1A and 2A because we had little power to
detect the few MetS resolution outcomes for this particular
analysis. The strength of association between follow-up time
and percentage of excess weight lost was also determined
using a correlation coefficient.
SENSITIVITY ANALYSIS
Sensitivity analyses were performed on our data using a
carry-forward method of imputation for patients lost to
follow-up. Patients excluded from the analysis because of
missing data (bariatric group, 35 patients; nonsurgical
group, 76 patients) were assumed to have MetS both at
baseline and at follow-up when determining what the
within-group change in MetS prevalence would have been
using this approach. We also determined the effect of ex-
cluding patients who had a baseline diagnosis of both dia-
betes and CV disease (74 patients [41%] in the surgical
group and 56 [36%] in the nonsurgical group) and those
with only a diagnosis of diabetes (58 patients [32%] in the
surgical group and 40 patients [25%] in the nonsurgical
group). P<.05 was considered statistically significant. All
analyses were performed using JMP for SAS (Windows
version 7.0.0; SAS Institute, Cary, NC).
RESULTS
The baseline characteristics of the cohorts are shown in
Table 1. Patients who underwent bariatric surgery had a
higher BMI and were more likely to be taking insulin than
patients in the nonsurgical group, but they had a similar
• www.mayoclinicproceedings.com 899
EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME

TABLE 1. Baseline Characteristics of Olmsted County Residents patients in the surgical group than in the nonsurgical group
Evaluated for Roux-en-Y Gastric Bypassa,b
had 4 MetS components (76 patients [42%] vs 45 patients
Surgical Nonsurgical P [29%]; P=.001) (Figure 1).
(n=180) (n=157) valuec
Age (y) 45±10 44±11 .39 SURGICAL GROUP
Female sex 143 (79) 113 (72) .11
Duration of follow-up (y) 3.4±2.5 3.5±2.6 .79 All MetS components improved at follow-up when mea-
Body mass index 49±9 44±6 <.001 sured as continuous or as categorical variables (Figure 2).
Excess weight (kg) 78±24 63±17.3 <.001 After bariatric surgery, the components with the greatest
Blood pressure (mm Hg)
Systolic 134±16 134±18 .79 decreases in prevalence were hypertriglyceridemia (42%,
Diastolic 80±10 77±10 .03 from 110 to 35 patients), glucose intolerance/diabetes mel-
Serum biochemical litus (39%, from 112 to 42 patients), and the obesity com-
parameters (mg/dL)d
Total cholesterol 200±39 208±45 .08 ponent (37%, from 180 to 114 patients). Mean lipid and
LDL-C 118±33 122±36 .26 blood pressure values decreased despite a decrease in the
HDL-C 45±11 45±14 .65 use of statins, diuretics, β-blockers, and ACEIs (Table 2).
Triglycerides 190±119 219±155 .10e
Glucose 118±38 121±51 .66
Creatinine 1.0±0.2 1.0±0.2 .32 NONSURGICAL GROUP
Diabetes 58 (32) 40 (25) .17 Although systolic blood pressure and overall lipid values
Ever smoker 25 (14) 29 (18) .25
Cardiovascular disease 29 (16) 23 (15) .71 improved in the nonsurgical group, the magnitude of im-
Medications provement was far lower than in the bariatric surgery
Statins 26 (14) 19 (12) .53 group; a marked increase in the use of statins and antihy-
β-Blockers 36 (20) 22 (14) .15
Calcium channel blockers 17 (9) 8 (5) .13 pertensive agents was also noted for the nonsurgical group
ACEI/ARB 39 (22) 36 (23) .78 at follow-up. The prevalence of MetS criteria other than
Diuretics 46 (26) 36 (23) .58 low HDL-C did not change. At follow-up, a greater number
Insulin 30 (17) 7 (4) <.001
Oral diabetes medications 26 (14) 24 (15) .83 of patients had type 2 diabetes mellitus and a greater pro-
MetS components 156 (87) 133 (85) .61 portion were taking insulin.
Obesity 180 (100) 157 (100) >.99
Hypertriglyceridemia 110 (61) 99 (63) .71
Low HDL-C 123 (68) 111 (71) .64 COMPARISON OF SURGICAL AND NONSURGICAL GROUPS
Elevated blood pressure 155 (86) 120 (76) .02 In both patients who underwent bariatric surgery and those
Impaired fasting glucose 112 (62) 88 (56) .25 who did not, the overall prevalence of MetS decreased
a
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin significantly (Figure 2) (surgical group, 58% decrease [from
receptor blocker; HDL-C = high-density lipoprotein cholesterol; 87% to 29%]; P<.001; nonsurgical group, 10% decrease
LDL-C = low-density lipoprotein cholesterol; MetS = metabolic syndrome.
b [from 85% to 75%]; P<.001). The absolute difference in
For continuous values, all values are represented as mean ± SD; for
categorical variables, values are represented as number (percentage) of prevalence reduction between groups was 48% (95% con-
patients and are rounded to the nearest integer, unless otherwise indicated. fidence interval [CI], 38%-58%; P<.001), yielding a rela-
c
The 2-sample t test with unequal variances and the Wilcoxon rank sum tive risk reduction with bariatric surgery of 0.59 (95% CI,
test were used for continuous data; the χ2 test or Fisher exact test was
used for nonparametric data. 0.48-0.67; P<.001). The number of patients needed to treat
d
SI conversion factors: To convert cholesterol values (total, HDL-C, in order to cure 1 patient with MetS with bariatric surgery
LDL-C) to mmol/L, multiply by 0.0259; to convert triglyceride values was 2.1. This was based on all patients with MetS at
to mmol/L, multiply by 0.0113; to convert glucose values to mmol/L,
multiply by 0.0555; to convert creatinine values to µmol/L, multiply by
baseline, calculating the difference between the proportion
88.4. of nonsurgical patients with MetS at follow-up (82%) mi-
e
P value based on logarithmic transformation of triglycerides. nus the proportion of surgical patients with MetS at follow-
up (34%), divided by the control proportion (82%). The
prevalence of MetS at baseline (156 patients [87%] vs 133 mean number of components decreased from 3.7 to 1.9
patients [85%]; P=.61) and a similar mean ± SD duration of (P<.001) in the bariatric surgery group and changed
follow-up (3.4±2.5 vs 3.5±2.6 years; P=.79). Follow-up slightly from 3.6 to 3.4 (P=.04) in the nonsurgical group.
ranged from 0.4 to 12.8 years for surgical patients (inter- Of the 157 nonsurgical patients, all met criteria for obesity
quartile range, 1.4-4.4 years) and from 0.4 to 13.8 years for at baseline, and 155 patients (99%) remained obese at
nonsurgical patients (interquartile range, 1.5-5.0 years). follow-up. In the surgical group, all 180 patients met crite-
Follow-up was less than 1 year in 14 patients (8%) who ria for obesity at baseline, whereas only 114 (63%) were
underwent surgery and in 15 patients (10%) who did not. obese at follow-up. After omitting BMI as a categorical
The correlation between duration of follow-up and percent- variable for MetS and defining MetS as 2 or more compo-
age of excess weight lost was 0.14. A greater number of nents, the prevalence in the surgical group decreased from

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 EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME

100 100

90 90

80 80 No. of
MetS
components
70 70
5
Prevalence (%)

60 60 4

50 50 3

40 40 2

30 30 1

20 20 0

10 10

0 0
Baseline Follow-up Baseline Follow-up

Surgical Nonsurgical

FIGURE 1. Baseline and follow-up prevalence of metabolic syndrome (MetS) components in surgical and nonsurgical patients.

158 patients (88%) to 67 patients (37%) (P<.001), whereas
in the nonsurgical group it decreased much less, from 138
patients (88%) to 117 patients (75%) (P<.001). Examina-
tion of our cohort, stratified by quartiles of follow-up time,
showed that the percentage of excess weight lost, as the
main predictor of MetS resolution, was highly significant
and did not change. Subsequently, performing multiple
logistic regression on the entire cohort of patients with
MetS at baseline showed that the percentage of excess
weight lost was the main predictor of MetS resolution
(Table 3). Again, results were no different after incorporat-
ing follow-up time as a covariate in the overall cohort after
adjusting for follow-up time (Model 1A and 2A). Separate
examination of the odds ratios of MetS resolution in the

100 100
*

90 90
* *
80 * 80
*
70 70
*
Prevalence (%)

* * 60
60

50 50

40 40

30 30

20 20

10 10

0 0
Obesity TG HDL-C HTN Glucose MetS Obesity TG HDL-C HTN Glucose MetS
Surgical Nonsurgical

FIGURE 2. Change in the prevalence and in each of the 5 components of the metabolic syndrome as defined by the American Heart
Association/National Heart, Lung, and Blood Institute. Dark bars represent baseline prevalence, and lighter bars represent
prevalence at follow-up. Significant changes (P<.05) are represented by an asterisk. HDL-C = high-density lipoprotein cholesterol;
HTN = hypertension; MetS = metabolic syndrome; TG = triglycerides.

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EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME

TABLE 2. Change in Parameters from Baseline to Follow-up 1 year were excluded for this particular analysis. Of the
in Olmsted County Residents Referred for Roux-en-Y
remaining 143 patients (79%) with a baseline diagnosis of
Gastric Bypassa,b
MetS, 45 patients (31%) did not have resolution of their
Surgical Nonsurgical P MetS during follow-up and were considered MetS nonre-
(n=180) (n=157) valuec
sponders. The mean number of components decreased
Age (y) 3.4±2.5 3.5±2.6 .74 from 3.9 to 1.3 (P<.001) in the MetS responders and from
Body mass index –16±6 –0.1±6.0 <.001
Excess weight (kg) –44±17 –0.3±16 <.001
4.2 to 3.5 (P<.001) in the MetS nonresponders. The num-
Excess weight lost (%) 59±20 –0.2±29 <.001 ber of MetS responders fulfilling the obesity criterion de-
Blood pressure, mm Hg creased from 98 patients (100%) to 51 patients (52%)
Systolic –13±18 –6±21 <.001 (P<.001), whereas the number of MetS nonresponders ful-
Diastolic –8±13 –2±13 <.001
Serum biochemical
filling the obesity criterion decreased from 45 patients
parameters (mg/dL)d (100%) to 40 (89%) (P=.02). These MetS nonresponders
Total cholesterol –46±39 –15±43 <.001 were older and had a higher baseline BMI, a lower percent-
LDL-C –41±34 –13±34 <.001 age of excess weight lost, higher serum levels of TGs,
HDL-C 9±11 4±11 <.001
Triglycerides –80±103 –44±112 .001 higher fasting blood glucose concentrations, a greater
Glucose –24±34 –4±47 <.001 prevalence of baseline diabetes mellitus, and increased use
Creatinine –0.05±0.15 0±0.15 .02 of ACEIs or ARBs (Table 4). No differences in the indi-
Diabetes (%) –37 (–21) 14 (9) <.001 vidual components of MetS at baseline were observed.
Cardiovascular disease (%) 4 (2) 6 (4) .39
Medications Percentage of excess weight lost was a highly significant
Statins –14 (–7) 31 (20) <.001 predictor of MetS resolution, even after adjusting for fol-
β-Blockers –15 (–8) 11 (7) <.001 low-up time (Table 3).
Calcium channel blockers –1 (–1) 1 (1) .75
ACEIs/ARBs –9 (–5) 21 (13) <.001
Diuretics –17 (–9) 17 (11) <.001 SENSITIVITY ANALYSIS
Insulin –24 (–13) 12 (8) <.001 Our sensitivity analysis, which assumed that patients with
Oral diabetes medications –24 (–13) –14 (–9) .29 missing data would not have MetS resolution at follow-up,
a
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin showed a 49% reduction in MetS prevalence in the 215
receptor blocker; HDL-C = high-density lipoprotein cholesterol; LDL-C = patients in the bariatric cohort, from 194 (90%) to 88
low-density lipoprotein cholesterol. patients (41%) vs a 7% reduction in MetS prevalence in the
b
Values are mean difference ± SD for continuous variables. Differences
in each cohort represent ValueFOLLOW-UP – ValueBASELINE. For categorical 233 patients in the nonsurgical group, from 209 (90%) to
values, the change in the number of patients (Follow-up – Baseline) 193 patients (83%). In another sensitivity analysis, after
renormalized to the baseline number of patients in each cohort is repre- excluding patients with a baseline diagnosis of both diabe-
sented (percentage) and is rounded to the nearest integer, unless other-
tes mellitus and CV disease, no differences in baseline
wise indicated. A negative value represents an improvement in the vari-
able for continuous data and a reduction in the net number (% reduction) prevalence of MetS (P>.99) were observed. Of the 101
of patients for categorical data. nonsurgical patients, 79 (78%) had MetS at baseline and 66
c
The 2-sample t test for unequal variances and the Wilcoxon rank sum (65%) at follow-up (P=.02). In the surgical cohort, of the
test were used to test the differences between continuous data for surgi-
cal and nonsurgical patients; the Cochran-Armitage trend test was used
106 patients without baseline diabetes or CV disease, 83
for categorical variables. (78%) had MetS at baseline compared with 19 (18%) at
d
SI conversion factors: To convert cholesterol (total, HDL-C, LDL-C) follow-up (P<.001). Results were similar after exclusion of
values to mmol/L, multiply by 0.0259; to convert triglyceride values to patients with baseline diabetes mellitus.
mmol/L, multiply by 0.0113; to convert glucose values to mmol/L,
multiply by 0.0555; and to convert creatinine values to µmol/L, multiply
by 88.4.
DISCUSSION
surgical group (Table 3) and nonsurgical group (data not Our population-based study shows that MetS is a largely
shown) for percentage of excess weight lost as our primary reversible phenomenon in patients with class II to III
predictor revealed no differences between these values af- obesity and that reversibility of MetS depends more on the
ter adjustment for follow-up time. All the above analyses percentage of excess weight lost than on other clinical or
suggest that follow-up time was not a significant contribu- demographic characteristics. Although the reversibility
tor to MetS resolution. could be influenced by or associated with factors such as
age, baseline serum TG levels, and baseline diabetes status,
SURGICAL METS RESPONDERS VS METS NONRESPONDERS these factors, although significant in our univariate analy-
Of the 156 patients who underwent bariatric surgery and sis at follow-up, were not as strongly predictive for MetS
had MetS at baseline, 13 (8%) with a follow-up of less than resolution as percentage of excess weight lost. This asso-

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 EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME

TABLE 3. Multivariate Logistic Regression Models Identifying Predictors of MetS Resolution

in Patients With a Follow-up Greater Than 1 Year a,b
Surgical responders vs nonresponders
Overall cohort with MetS at baseline with MetS at baseline
Model 1 Model 1Ac Model 2 Model 2Ac Model 1 Model 1Ac
P P P P P P
OR value OR value OR value OR value OR value OR value
Age 0.94 .001 0.94 .001 0.95 .003 0.95 .003 0.93 .009 0.93 .009
Male sex 1.07 .86 1.09 .83 0.87 .69 0.85 .66 1.24 .71 1.23 .73
Triglycerides 0.28 .001 0.28 .001 0.35 .002 0.35 .002 0.33 .03 0.33 .03
Diabetes (yes/no) 0.32 .003 0.32 .003 0.26 <.001 0.26 <.001 0.41 .06 0.41 .06
ACEI/ARB 0.40 .02 0.40 .02 0.54 .11 0.55 .11 0.34 .03 0.34 .03
HDL-C NA NA NA NA NA NA NA NA 1.02 .37 1.02 .38
% EWLd 1.05 <.001 1.05 <.001 1.03 <.001 1.03 <.001 1.05 <.001 1.05 <.001
5% change in % EWL 1.26 <.001 1.26 <.001 1.17 <.001 1.18 <.001 1.28 <.001 1.28 <.001
Follow-up time NA NA 0.98 .75 NA NA 1.03 .65 NA NA 1.01 .92
a
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; EWL = excess weight lost; HDL-C = high-density lipoprotein
cholesterol; MetS = metabolic syndrome; NA = not applicable; OR = odds ratio.
b
Separate models were constructed for the overall cohort consisting of both surgical and nonsurgical patients with MetS at baseline and for patients
undergoing bariatric surgery who had MetS at baseline. All patients had a follow-up of greater than 1 year. MetS was defined as 3 or more of 5 components
of American Heart Association/National Heart, Lung, and Blood Institute–defined MetS in Model 1. Model 2 consists of 2 or more of 4 components
(excluding the obesity component). Covariates in the overall cohort for Models 1 and 2 were age, sex, baseline serum triglyceride levels, presence of
diabetes mellitus at baseline (yes/no), use of ACEIs or ARBs at baseline (yes/no), and percentage of EWL. For the surgical cohort alone (MetS responders
and MetS nonresponders), HDL-C was added as a covariate in the multivariate analysis for Model 1. Follow-up time was included as a covariate in the
multiple logistic regression models labeled with the suffix “A.”
c
Models including time as a covariate.
d
Per 1% unit change in excess weight lost.

ciation persisted even in the BMI-independent definition of
MetS, suggesting its importance in relation to the other
MetS components. Patients in the structured, multidis-
ciplinary, nonsurgical program showed minimal weight
changes associated with improvements in systolic blood
pressure and lipid parameters; however, many of these
improvements may have been related to more aggressive
pharmacotherapy, given that a considerably greater num-
ber of nonsurgical patients were taking statins or antihyper-
tensive agents at follow-up.
Relatively few studies have used established MetS crite-
ria in evaluating outcomes after bariatric surgery.15,16 All
confirm our results, showing marked reductions in the
prevalence of MetS and in the number of MetS compo-
nents. Several studies have examined non-American popu-
lations,16-19 in whom RYGB often is not used. Of studies
performed in the United States with RYGB, Madan et al20
showed a decrease in MetS as defined by Adult Treatment
Panel (ATP) III from 78% to 2%; however, this study was
relatively small, did not have a nonsurgical group, and had
a limited follow-up of 1 year. A study by Mattar et al21
found a decrease from 70% to 14% in a series of 70 pa-
tients. Although their follow-up was somewhat longer,
their study had limitations similar to those of the Madan
study. Morinigo et al22 examined RYGB using criteria from
the ATP III, showing a decrease in MetS prevalence from
55% to 36% at 6 weeks and to 11% at 52 weeks, but their
study was limited to 36 patients with no control group. Our
study confirms and expands these findings with the use of
state-of-the-art epidemiologic methods supporting these
conclusions.
To our knowledge, our study is the first to assess predic-
tors of MetS resolution in patients with class II to III
obesity, showing that percentage of excess weight lost is
the main predictor of whether a patient will be cured of
MetS at follow-up. The use of an obesity-independent defi-
nition of MetS confirmed the importance of excess weight
lost on resolution of MetS. Our study provides robust data
to practicing clinicians about the benefits of counseling
weight reduction in MetS patients.
Our results have important clinical implications because
they further our understanding of the possible reversibility
of MetS with weight loss. Does this reduction in MetS
prevalence after bariatric surgery, and specifically after
RYGB, reduce CV disease? No studies have used risk-
prediction functions in patients with MetS after bariatric
surgery. However, in the past year, several studies 23,24 have
projected significant reductions in CV risk and death, in-
cluding our own study that used risk modeling derived
from the National Health and Nutrition Examination Sur-
vey and applied it to this specific cohort,25 estimating that 4
overall deaths and 16 CV events would be prevented by
bariatric surgery per 100 patients at 10 years. The few
studies that have examined specifically the decrease of
actual CV events and overall mortality likely underesti-
mate the value of bariatric surgery because of lack of

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EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME

TABLE 4. Baseline Characteristics of 143 Roux-en-Y Gastric study of 9949 patients who had undergone RYGB showed
Bypass Patients With MetS at Baseline, Stratified by
MetS Responders vs Nonresponders a 40% survival benefit for them compared with obese
With a Follow-up of Greater Than 1 Yeara,b,c control patients;29 cause-specific mortality due to coro-
MetS
nary artery disease was reduced by 56%. Furthermore, the
Responders Nonresponders P
Swedish Obesity Study showed a risk reduction of 29% at
(n=98) (n=45) valued 10 years.30 Mortality rates could decrease after bariatric
surgery in part because of the total or partial resolution of
Age (y) 43±10 48±10 .009
Female sex (%) 77 (79) 35 (78) .91 MetS.
Body mass index 49±8 52±11 .05 Bariatric surgery decreases fat stores31 and offers an
Excess weight (kg) 76±24 82±25 .20 opportunity to better understand the reversibility of MetS
Excess weight lost (%) 63±20 49±18 <.001
Blood pressure (mm Hg) with profound weight loss. Weight loss is known to re-
Systolic 134±16 135±16 .82 duce blood leptin and ghrelin levels, increase adiponectin
Diastolic 80±10 79±11 .74 levels, improve insulin sensitivity, and reduce fatty acid
Serum biochemical
parameters (mg/dL)e turnover; it is also associated with a decrease in systemic
Total cholesterol 199±41 199±37 .62 inflammation and improved endothelial function.32 Fur-
LDL-C 119±33 110±28 .12 ther investigation is needed to determine whether incretin
HDL-C 44±9 41±11 .07
Triglycerides 177±88 254±169 <.001 levels, insulin sensitivity, and glucose intolerance are af-
Glucose 118±38 133±40 .03 fected differently by a duodenal bypass procedure vs gas-
Creatinine 1± 0.2 1±0.2 .71 tric banding.
Diabetes (%) 28 (29) 28 (62) <.001
Ever smoker (%) 18 (18) 5 (11) .27 The main strength of our study is its use of the Roches-
Cardiovascular ter Epidemiology Project to ascertain the outcomes of all
disease (%) 15 (15) 9 (20) .49 patients referred for RYGB in Olmsted County, Minne-
Medications
Statins 16 (16) 7 (16) .91 sota. By using a population-based cohort, we minimized
β-Blockers 19 (19) 12 (27) .33 the selection and referral bias often observed at tertiary
Calcium channel care institutions performing this surgery. Previous studies
blockers 10 (10) 6 (13) .58
ACEI/ARB 15 (15) 16 (36) .006 have shown reasonable extrapolation of data to other
Diuretics 26 (27) 14 (31) .57 parts of the United States using this population.12 The
Insulin 16 (16) 10 (22) .40 ability to abstract a patient’s entire medical record en-
Oral diabetes
medications 13 (13) 7 (16) .71 sured that all information and outcomes relevant to this
MetS component study were available. Although a few studies have exam-
Obesity 98 (100) 45 (100) >.99 ined the effect of bariatric surgery in patients with MetS,
Hypertriglyceridemia 65 (66) 34 (76) .27
Low HDL-C 72 (73) 37 (82) .25 none have had a nonsurgical group whose characteristics
Elevated blood were similar to surgical patients, and many have been
pressure 85 (87) 41 (91) .45 performed in Europe, where alternative techniques, in-
Impaired fasting
glucose 65 (66) 36 (80) .10 cluding biliopancreatic bypass and gastroplasty, are used.
a
No recent studies have used the most updated MetS crite-
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin
receptor blocker; HDL-C = high-density lipoprotein cholesterol; LDL- ria published by the AHA/NHLBI. Most studies of MetS
C = low-density lipoprotein cholesterol; MetS = metabolic syndrome. parameters after RYGB examine outcomes up to 1 year,
b
Responders are defined as patients undergoing Roux-en-Y gastric by- whereas our study provided follow-up of more than
pass who have MetS at baseline and are cured of MetS at follow-up.
c
All variables are mean ± SD for continuous variables or number (per- 3 years. The use of an obesity-independent definition also
centage) of patients for categorical variables and are rounded to the lends credence to our results. The sensitivity analysis
nearest integer, unless otherwise indicated. we performed to determine the effect of missing pa-
d
The 2-sample t test with unequal variances and Wilcoxon rank sum test
were used for continuous data; the χ2 test or Fisher exact test was used tients on our intragroup results ensures that, in a worst
for categorical data. P values are testing the differences in baseline case scenario in which these missing patients had no
parameters between MetS responders and MetS nonresponders. metabolic improvements, the effect on our study results
e
SI conversion factors: To convert cholesterol values (total, HDL-C, LDL-C)
to mmol/L, multiply by 0.0259; to convert triglyceride values to mmol/L, would be minimal, allowing adequate generalization of
multiply by 0.0113; to convert glucose values to mmol/L, multiply by these results.
0.0555; and to convert creatinine values to µmol/L, multiply by 88.4. As with any retrospective study, recording and measure-
ment bias are inherent issues in the study design. We had
follow-up information or use of hospital controls.26-28 Re- no control over when patients had their laboratory or clini-
cently, 2 studies have confirmed our previously published cal assessment. Information was unavailable regarding
estimated risk reduction after bariatric surgery.29,30 One known confounders, such as exercise, dietary habits, diag-

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For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.

nosis or management of obstructive sleep apnea, and leptin
or insulin sensitivity. However, these issues would be
present in both groups and at both points in time. The
variability in the follow-up time created inherent chal-
lenges in analyzing our data. As a rule, Cox proportional
hazards models should be used in inception cohorts in
which time to last follow-up is variable, patients are ex-
posed to the predictor of interest from the beginning of the
follow-up, the risk is proportional to the time of follow-up,
and the timing of the outcome is well known. In our study
group, none of the last 3 assumptions were met. Weight
loss, particularly with bariatric surgery, usually occurs in a
nonlinear fashion within the first year,11 and subsequent
weight regain is minimal. However, once it was shown that
the length of follow-up did not affect the association be-
tween percentage of excess weight lost and the resolution
of MetS, logistic regression appeared to be more appropri-
ate than the Cox proportional hazards model. Acknowl-
edging the limitations of both approaches, we attempted to
prove that percentage of excess weight lost remained sig-
nificant in each of these analyses by eliminating patients
with less than 1 year of follow-up and stratifying the re-
maining cohort by follow-up time. Adjusting our models
by follow-up time also confirmed these results. This ap-
proach suggests that percentage of excess weight lost re-
mains the main predictor of MetS resolution at 1-year
follow-up.
The decision to undergo bariatric surgery cannot be
allocated randomly. We made no attempt to match our
nonsurgical group to our bariatric surgery group. Ideally, in
a matched analysis we would have required a greater num-
ber of nonsurgical patients, which was not possible in this
retrospective study. In addition, our nonsurgical group
should not be considered a true control group but instead a
population-based cohort of patients referred for surgical
intervention who did not undergo operative treatment.
Therefore, our results may not be generalizable to all
patients attempting weight loss with nonsurgical ap-
proaches. Furthermore, very few of the nonsurgical pa-
tients achieved a weight loss that exceeded the mean
weight loss of the surgical group, suggesting that our
results would not be significantly affected if we elimi-
nated specific groups of patients, such as the
underinsured. Our findings can be applied only to patients
with class II to III obesity who have undergone evaluation
for RYGB bariatric surgery—the patient population that
is most eligible for bariatric procedures10—and hence
cannot be extrapolated to nonobese patients with MetS or
to patients treated with other types of bariatric proce-
dures, including gastric banding.
Although MetS is thought to lead to the development of
both type 2 diabetes mellitus and CV disease, we included
Mayo Clin Proc. • August 2008;83(8):897-906
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EFFECT OF BARIATRIC SURGERY ON THE METABOLIC SYNDROME
patients with both these diagnoses. One of the primary
controversies in the MetS literature is the inclusion of
diabetes mellitus in ATP definition criteria. Our study
showed that results were not altered after excluding pa-
tients with preexisting diabetes mellitus or CV disease at
baseline in our sensitivity analysis.
CONCLUSION
Bariatric surgery is an effective means of reversing or
controlling MetS in patients eligible for surgically induced
weight loss. This current study provides strong evidence
that percentage of excess weight lost after RYGB is a
primary contributor to reduced MetS prevalence and is
independent of the obesity component. We suggest that
RYGB should be considered as a treatment option in pa-
tients with MetS that has not responded to conservative
measures.
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