Article

Cardiovascular Events After Bariatric Surgery in Obese Subjects With Type 2 Diabetes

Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Diabetes care (Impact Factor: 8.42). 08/2012; 35(12). DOI: 10.2337/dc12-0193
Source: PubMed

ABSTRACT

OBJECTIVE
Obese individuals with type 2 diabetes have an increased risk of cardiovascular disease. The effect of bariatric surgery on cardiovascular events in obese individuals with type 2 diabetes remains to be determined. The Swedish Obese Subjects (SOS) study is a prospective, controlled intervention study that examines the effects of bariatric surgery on hard end points. The aim of the present study was to examine the effect of bariatric surgery on cardiovascular events in the SOS study participants with type 2 diabetes.RESEARCH DESIGN AND METHODS
All SOS study participants with type 2 diabetes at baseline were included in the analyses (n = 345 in the surgery group and n = 262 in the control group). Mean follow-up was 13.3 years (interquartile range 10.2-16.4 years) for all cardiovascular events.RESULTSBariatric surgery was associated with a reduced myocardial infarction incidence (38 events among the 345 subjects in the surgery group vs. 43 events among the 262 subjects in the control group; log-rank P = 0.017; adjusted hazard ratio (HR) 0.56 [95% CI 0.34-0.93]; P = 0.025). No effect of bariatric surgery was observed on stroke incidence (34 events among the 345 subjects in the surgery group vs. 24 events among the 262 subjects in the control group; log-rank P = 0.852; adjusted HR 0.73 [0.41-1.30]; P = 0.29). The effect of surgery in reducing myocardial infarction incidence was stronger in individuals with higher serum total cholesterol and triglycerides at baseline (interaction P value = 0.02 for both traits). BMI (interaction P value = 0.12) was not related to the surgery outcome.CONCLUSIONS
Bariatric surgery reduces the incidence of myocardial infarction in obese individuals with type 2 diabetes. Preoperative BMI should be integrated with metabolic parameters to maximize the benefits of bariatric surgery.

Full-text

Available from: Peter Jacobson
Cardiovascular Events After Bariatric
Surgery in Obese Subjects With
Type 2 Diabetes
STEFANO ROMEO, MD, PHD
1
CRISTINA MAGLIO, MD
1
MARIA ANTONELLA BURZA, MD
1
CARLO PIRAZZI, MD
1
KAJSA SJÖHOLM, PHD
1
PETER JACOBSON, MD, PHD
1
PER-ARNE SVENSSON, PHD
1
MARKKU PELTONEN, PHD
2
LARS SJÖSTRÖM, MD, PHD
1
LENA M.S. CARLSSON, MD, PHD
1
OBJECTIVE dObese individuals with type 2 diabetes have an increased risk of cardiovascular
disease. The effect of bariatric surgery on cardiovascular events in obese individuals with ty pe 2
diabetes remains to be determined. Th e Swedish Obese Subjects (SOS) study is a prospective ,
controlled intervention study that examines the effects of b ariatric surgery on hard end points.
The aim of the present study was to examine the effect of bariatric surgery on cardiovascular
events in the SOS study participants with type 2 diabetes.
RESEARCH DESIGN AND METHODSdAll SOS stud y participants with type 2 diabetes
at baseline were included in the analyses (n = 345 in the surg ery group and n = 262 in the control
group). Mean follow-up was 13.3 years (interquartile range 10.216.4) for all cardiovascular
events.
RESULTSdBariatric surgery was associa ted with a reduced myocardial infarction incidence
(38 events among the 345 subjects in the surgery group vs. 43 events among the 262 subjects in
the control group; log-rank P = 0.017; adjusted hazard ratio [HR] 0.56 [95% CI 0.3 40.93]; P =
0.025). No effect of bariatric surgery was observed on stroke incidence (34 events among the 345
subjects in the surgery group vs. 24 events among the 262 subjects in the control group; log-rank
P = 0.852; adjusted HR 0.7 3 [0.411.30]; P = 0.29). The effect of surgery in reducing myocardial
infarction incidence was stronger in individuals with higher serum total cholesterol and triglyc -
erides at baseline (interaction P value = 0.02 for both traits). BMI (inter action P value = 0 .12) was
not related to the surgery outcome.
CONCLUSIONSdBariatric surgery reduces the incidence of myocardial infarction i n obese
individuals with type 2 diabetes. Preoperative BMI should be integrated with metabolic param-
eters to maximize the benets of bariatric surgery.
Diabetes Care 35:2613 2617, 2012
O
besity is a growing burden for
Western countries with approxi-
mately one-third of the population
being affected in the U.S. (1). Excess body
weight is associated with increa sed inci-
dence of type 2 diabetes and cardiovascu-
lar disease (24). To dat e, bariatric
surgery is the most effective treatment to
achi eve wei ght loss in obese individuals
(5). The Swedish Obese Subjects (SOS)
study is a nonr andomized but controlled,
prospective, interventional trial on the ef-
fect o f b ariatric surgery on mortal ity and
morbidity compared with conventional
obesity treatment (6). We recently reported
that bariatric surgery was assoc iated
with a decreased incidence of cardiovas-
cular events in the overall SOS study (7).
In individuals with type 2 diabetes,
bariatric surgery results in sustained weight
loss and also reduces blood glucose values
(810). The American Diabetes Association
(11), International Diabetes Federation
(12), and other organizations (13,14) rec-
ommend bariatric surgery for adults with
type 2 diabetes and BMI $35 kg/m
2
,espe-
cially for those whose diabetes is difcult to
control with a lifestyle and pharmacologi-
cal approach. However, data on the long-
term benets of bariatric surgery on hard
end points in individuals with type 2 dia-
betes are not available. Whether the meta-
bolic improvement results in a reduced
number of cardiovascular events in obese
individuals with type 2 diabetes remains to
be determined. Therefore, the aim of the
present report was to examine the effect
of bariatric surgery on cardiovascular
events in SOS study participants with
type 2 diabetes at baseline.
RESEARCH DESIGN AND
METHODS
Study design
The SOS study has been previously de-
scribed in detail (57,15). In brief, the SOS
study is a prospective, nonrandomized,
controlled interventional trial on the effect
of bariatric surgery on mortality and mor-
bidity compared with conventional obesity
treatment. A total of 4,047 obese individu-
als were enrolled from 1 September 1987
to 31 January 2001. Among these subjects,
2,010 underwent bariatric surgery, and
a contemporaneously matched control
group of 2,037 individuals was created us-
ing18matchingvariables.Writtenin-
formed consent has been obtained by all
study participants. All clinical investiga-
tions have been conducted according to
the principles expressed in the Declaration
of Helsinki. Seven local ethics review
boards approved SOS study protocol. In-
clusion and exclusion criteria were identi-
cal for both study groups. Inclusion
criteria were between 37 and 60 years of
age and BMI $34 kg/m
2
for men and $38
kg/m
2
for women. The exclusion criteria
ccccccccccccccccccccccccccccccccccccccccccccccccc
From the
1
Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic
Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and the
2
Chronic Dis-
ease Epidemiology and Prevention Unit, Department of Chronic Disease Prevention, National Institute for
Health and Welfare, Helsinki, Finland.
Corresponding author: Stefano Romeo, stefano.romeo@wlab.gu.se.
Received 30 January 2012 and accepted 30 May 2012.
DOI: 10.2337/dc12-0193. Clinical trial reg. no. NCT01479452, clinicaltrials.gov.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10
.2337/dc12-0193/-/DC1.
L.S. and L.M.S.C. contributed equally to this work.
© 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly
cited, the use is educational and not for prot, and the work is not altered. See http://creativecommons.org/
licenses/by-nc-nd/3.0/ for details.
See accompanying commentary, p. 2424.
care. diabetesjournals.org DIABETES CARE, VOLUME 35, DECEMBER 2012 2613
Cardiovascular and Metabolic Risk
ORIGINAL ARTICLE
Page 1
were earlier surgery for gastric or duode-
nal ulce r, earlier bariatric surgery, gastric
ulcer during the past 6 months, ongoing
malignancy, active malignancy during the
past 5 years, myoc ardial infarction during
the past 6 months, bulimic eating pattern,
drug or alcohol abuse, psychiatric or coop-
erative problems contraindicating bariatric
surgery, and other contraindicating condi-
tions (such as chronic glucocorticoid or
anti-inammatory treatment) (6). Subjects
with hypertension, diabetes, dyslipidemia,
or myocardial infarction and stroke .6
months before recruitment were not ex-
cluded. Participants were examined at
matching, at baseline, and after 0.5, 1, 2,
3, 4, 6, 8, 10, 15, and 20 years. Biochemical
parameters were measured at the matching
and baseline examinations and at 2-, 10-,
15-, and 20-year follow-up. Fasting blood
samples were obtained in the morning after
an overnight fast as previously described
(6). Type 2 diabetes was dened as fasting
blood glucose $6.1 mmol/L (when using
fasting plasma glucose, the cutoff values are
$7.0 mmol/L or 126 mg/dL) (16,17) and/
or self-reported therapy with glucose-
lowering medications at baseline.
The current report is based on 607
subjects with type 2 diabetes a t baseline:
345 subjects underwent bariatric surgery
(227 vertical-banded gastroplasty, 61 gas-
tric banding, and 57 gastric bypass), and
262 sub jects in the control group received
the standard obesity and diabetes treat-
ment at their centers of registration.
Study end points
The end points analyzed in the current
report were fatal and nonfatal cardiovas-
cular events (myocardial infarction and
stroke, whichever came rst) as well as
myocardial infarction and cerebral stroke
analyzed separately. These end points,
which were predened in the original
study protocol from 1987 for the total
SOS study population, are analyzed here
in the SOS participants with type 2 di-
abetes at baseline. The following ICD-9/
ICD-10 codes were used: myocardial in-
farction, 410/I21, I22; intracerebral bleed-
ing, 431/I61; cerebral artery occ lusion,
433, 434/I63, I65, and I66; and acute
but nondened stroke in terms of bleeding
or occlusion, 436/I64. Angina pectoris,
claudication, transitory ischemic attack,
and subarachnoid hemorrhage were not in-
cluded in the analyses. Information about
the end points was obtained by cross-
checking social security numbers from
the SO S database with the Swedish Na-
tional Patient Register, the Cause of Death
Register, and the Register of the Total Pop-
ulation. The information in the health reg-
istries was completed until 31 December
2009. On this cutoff date of the analysis,
the median follow-up time was 13.3 years
(interquartile range 10.216.4 years).
Statistical analysis
Base line characteristics and changes over
time were described as mean 6 SD. Base-
line continuous variables and 2-year
follow-up changes in the treatment
groups were compared by using a linear
regression model adjusted for age, sex,
and BMI. A x
2
test was used to compare
categorical variables.
Time of progression to end points was
compared between the surgery and control
groups with Kaplan-Meier estimates of
cumulative incidence rates. Survival distri-
butions in the two treatment groups were
compared using a log-rank test. Cox pro-
portional hazards models based on baseline
data were also used to evaluate time to
cardiovascular event. Hazard ratios (HRs)
were also adjusted for cardiovascular dis-
ease risk factors. Continuous traits HRs
have been expressed per 1-SD difference
at baseline in the SOS population with type
2 diabetes.
For baseline risk factortreatm ent in-
teractio n analysis, dichotomous variables
could have one of two values (for exam-
ple, sex: men/women), where as for the
other parameters, the interaction test
was calculated using the original conti n-
uous variables. N o adjustment for multi-
ple testin g was performed. The number of
surgical proc edures needed to prevent
one myocardial infarction was calculated
as the reciprocal of the absolute risk dif-
ference between subjects from the surgery
and control gro ups, and it was estimated
in a 15-year follow-up.
Statistical analyses were carried out
using the Statistical Package for Social
Science (version 18.0.0, SPSS, Inc., Chi-
cago , IL). Intention-to-trea t principle was
applied in all calculations. Two-sided P
values ,0.05 were considered as statisti-
cally signicant.
RESULTS
Baseline characteristics
All SOS participants with type 2 diabetes at
baseline (n = 607) were included in the
analysis. Characteristics of the 345 surgi-
cally treated subjects and the 262 matched
controls that had type 2 diabetes at baseline
are shown in Table 1. The mean age of the
surgery group was lower compared with
the control group. The surgery group had
higher BMI, systolic blood pressure, dia-
stolic blood pressure, and total cholesterol
compared with the control group. No dif-
ferences in other parameters, including
blood glucose, insulin, HDL cholesterol,
triglycerides, smoking status, an d lipid-,
glucose-, and blood pressurelowering
medications, were observed. F urther-
more, at baseline, the proportion of sub-
jects previously affected by myocardial
infarction or cerebral stroke was not dif-
ferent between groups.
Weight and metabolic changes after
bariatric surgery
At 2 years, the proportion of individuals
with clinical and biochemical follow-up
was 89 and 79% in the surgery and
control groups, respectively. Mean 2-year
follow-up changes in weight and meta-
bolic parameters are described in Supple-
mentary Fig. 1. Bariatric surgery was
associated wi th a signicant decrease in
body weight, blood glucose, serum triglyc-
erides, and systolic and diastolic blood
pressure (P value for each tra it was
,0.001) and a signicant increase in
HDL cholesterol (P , 0.001) compared
with usual care. No signicant difference
in total cholesterol changes between the
surgery and control groups was observed.
Effect of bariatric surgery on
cardiovascular disease
Bariatric surgery was associated with re-
duced incidence of fatal and nonfatal car-
diovascular events. During the follow-up
period, 63 rst-time cardiovascular events
(myocardial infarction or stroke, whichever
came rst) occurred among 345 individu-
als in the surgery group compared with 65
events among 262 individuals in the con-
trol group (log-rank P = 0.010; unadjusted
HR 0.63 [95% CI 0.450.90]; P =0.010)
(Fig. 1A). After adjustment for baseline an-
thropometrical and clinical characteristics,
the HR for cardiovascular events was 0.53
(0.350.79; P = 0.002) (Table 2). In the
adjusted analyses, classical cardiovascular
risk factors (age, smoking, systolic blood
pressure, total cholesterol, and diabetes du-
ration) remained sign icantly associated
with an increased risk of cardiovascul ar
events (Table 2). Results were virtually
identical after excluding individuals in
whom myocardial infarction or stroke oc-
curred within 2 years from baseline (data
not shown).
Next, the incidence of myocardial in-
farction and stroke were assessed sepa-
rately. Bariatric surgery was associated with
2614 DIABETES CARE, VOLUME 35, DECEMBER 2012 care.diabetesjournals.org
Bariatric surgery, diabetes, and cardiovascular events
Page 2
lower incidence of myocardial infarction.
A total of 38 of the 345 individuals in the
surgery group and 43 of the 262 individ-
uals in the control group had myocardial
infarction during follow-up (log-rank P =
0.017; HR = 0.59 [95% CI 0.380.92]; P =
0.018) (Fig. 1B). After adjustment for base-
line anthropometrical and clinical charac-
teristics, the HR for myocardial infarction
was 0.56 (0.340.93; P =0.025)(Table2).
No signicant differences in the incidence
of myocardial infarction were found be-
tween the different surgical procedures
(vertical gastroplasty, gastric banding, and
gastric bypass) (Supplementary Fig. 2).
A total of 34 of the 345 individuals from
the surgery group and 24 of the 262 in-
dividuals from the control group had stroke
during follow-up. Bariatric surgery was not
associated with changes in the incidence of
cerebral stroke in unadjusted (log-rank P =
0.85; HR 0.95 [95% CI 0.561.61]; P =
0.85) (Fig. 1C) or adjusted analyses (HR
0.73 [0.411.30]; P = 0.29) (Table 2).
Risk factortreatment interaction
analyses and number needed to treat
To test if baseline characteristics were re-
lated to the treatment benetofbariatric
surgery with respect to myocardial
infarction, a subgroup analysis on baseline
risk factortreatment interaction was per-
formed. Specically, the relative treatment
effect and the trea tment interaction on
myocardial infarction incidence were as-
sessed after st ratifyi ng by sex, previo us
myocardial infarction, smoking, and glu-
cose-lowering medication and by the me-
dian of baseline age, BMI, weight, waist,
insulin, t otal cholesterol, triglycerides,
HDL cholesterol, blood pressure, and dia-
betes duration (Supplementary Table 1). In
diabetic subjects, the surgical treatment
benet with respect to myocardial infarction
events was signicantly associated with
baseline serum total c holesterol and
triglycerides (interaction P =0.02for
both), with a greater relative treatment
benet in subjects with higher total
cholesterol and triglycerides. In contrast,
the treatment benet of bariatric surgery
was not related to other clinical and meta-
bolic parameter traits, i nc l u d i n g B M I
(Supplementary Table 1). Still, when indi-
viduals were stratied by median of BMI
(40.6 kg/m
2
), a signicant protec tive ef-
fect of bariatric surgery was found in in-
dividuals below the median (HR 0.43
[95% CI 0.22 0.84]; P = 0.010) (Supple-
mentary Table 1).
Finally, the numb er needed to treat
(NNT) was calculated to estimate the
number of obese diabetic subj ects needed
Figure 1dCumulative incidence of cardiovas-
cular events in SOS subjects with diabetes at
baseline. A: There were 63 cardiovascular events
(CVEs) among the 345 subjects in the surgery
group (median follow-up = 13.9 years [10.716.9
years]), compared with 65 events among the 262
subjects in the control group (median follow up =
12.2 years [9.915.8 years]). CVEs: myocardial
infarction and stroke combined, whichever came
rst. B: Among the 345 subjects in the surgery
group, there were 38 myocardial infarctions
(MIs), compared with 43 among the 262 subjects
in the control group. C: Out of 345 subjects in the
surgery group, 34 had stroke, compa red with 24
of the 262 subjects in the control group.
Table 1dCharacteristics of SOS study participants with type 2 diabetes at baseline
Surgery Control
n 345 262
Male (%) 41 40
Age (years) 49 (6) 50 (6)*
Weight (kg) 123 (19) 116 (17)*
BMIx (kg/m
2
) 42 (5) 40 (5)*
SBP (mmHg) 151 (19) 144 (19)*
DBP(mmHg) 93(11) 87(11)*
Blood glucose (mg/dL) 156 (48) 156 (49)
Insulin (mU/L) 29 (19) 26 (18)
Total cholesterol (mg/dL) 229 (48) 222 (45)*
HDL cholesterol (mg/dL) 48 (12) 48 (11)
Triglycerides (mg/dL) 257 (193) 256 (211)
Smoking s tatus (%) 25 21
Lipid-lowering medications (%) 5 6
Blood pressurelowering medica tions (%) 48 49
Glucose-low ering medica tions (%) 48 53
Diabetes duration (years) 3 (5) 3 (5)
Previous myocardial infarction (%) 5 4
Previous cerebral stroke (%) 1 2
Surgical procedure (%) 100 0
Vertical gastr oplasty 66 d
Gastric banding 18 d
Gastric bypass 16 d
Data are shown as means (SD) or proportion. Baseline continuous variables in the treatment groups were
compared by using a linear regression model adjusted for age, sex, and BMI. A x
2
test was used to compare
categorical variables. To convert glucose to mmol/L, multiply by 0.0555; total and HDL cholesterol to mmol/L,
multiply by 0.0259; triglycerides to mmol/L, multiply by 0.0113. DBP, diastolic blood pressure; SBP, systolic
blood pressure. xBMI is calculated as weight in k ilograms div ided by the square of height in meters. *P value
,0.05, surg ery vs. control group.
care. diabetesjournals.org DIABETES CARE, VOLUME 35, DECEMBER 2012 2615
Romeo and Associates
Page 3
to undergo bariatric surgery to prevent one
myocardial infarction over 15 years (Sup-
plementary Table 1). The estimated NNT
in the overall diabetic SOS population was
16 (Supplementary Table 1). No signicant
difference in NNT after stratifying the pop-
ulation by baseline characteristics was
found (Supplementary Table 1).
CONCLUSIONS dThis is the rst
prospective report showing that bariatric
surgery reduces the incidence of myocar-
dial infarction in obese subjects with type
2 d iabetes. In obese subjects with type 2
diabetes, bariatric surgery was associated
with a lower incidence of cardiovascular
events, and the benecial effect of the
surgical treatment was also prese nt after
adjustment for baseline parameters.
When analyzed separately, bariatric sur-
gery was associated with a reduced in-
cidence of myocardial infarction, but no
effect was observed on stroke incidence.
We have recentl y shown bariatric surgery
in the overall SOS study cohort was
associated with reduced incidence of car-
diovascular events and myocardial
infarction or stroke when analyzed sepa-
rately; however, the eff ect size on stroke
was modest (7). The absence of an effect
on stroke incidence in subjects w ith type
2 diabetes at baseline co uld be explained
by low statistical power given that only
15% (only those with ty pe 2 diabetes at
baseline) of the overall SOS study partic-
ipants wer e included.
Several metabolic variables (blood glu-
cose, circulating lipids, and blood pressure)
were markedly improved in the surgery
group. These data are in line with previous
reports on the metabolic changes after
bariatric surgery (5,9,18,19). However,
this is the rst study to demonstrate that
the benecial eff ects of b ariatric surgery
on cardiovascular risk factors are also
followed by reduced risk of myocardial in-
farction in individuals with type 2 diabe-
tes. The NNT shows that 16 individuals
with type 2 diabetes need to be operated to
prevent one myocardial infarction over a
period of 15 years. In the surgery group,
no difference in the incidence of myocar-
dial infarction was observed across the
three different surgical procedures; how-
ever, our study was not statistically pow-
ered to detect such difference.
Interestingly, in our study, bariatric
surgery was associated with a reduction of
myocardial infarction incidence in dia-
betic individuals with BMI below the
median (40.6 kg/m
2
). This result corrob-
orates the guidelines from the American
Diabetes Association (11), International
Diabetes Federation (12), and other or-
ganizations (13,14) in which bariatric sur-
gery is considered as a therapeutic option
in diabetic subjects with BMI ,40 kg/m
2
.
Furthermore, the risk factortreatme nt in-
teraction analysis showed that the effect of
surgery on myocardial infarction was
greater in participants with higher total cho-
lesterol and triglyceride levels, possibly sug-
gesting that, in obese diabetic individuals,
those with dyslipidemia should be priori-
tized. Moreover, in the previously reported
analyses on the overall SOS study cohort
(7), baseline fasting insulin levels rather
than BMI predicted the surgery treatment
benet on cardiovascular event. Taken to-
gether, these results suggest that to maxi-
mize the benets, metabolic p arameters
should be used to select obese patients for
surgery (7,20).
A limitation of the current report is that
the SOS study intervention was not ran-
domized for ethical reasons due to high
postoperative mortality in the 1980s. An-
other limitation of our study is that we
performed a post hoc analysis, selecting
only individuals with type 2 diabetes at
baseline. However, myocardial infarction
and stroke were predened secondary end
points for the overall SOS population in
the original study protocol. Ideally, longi-
tudinal, randomized, controlled trials (e.g.,
obese diabetic individuals selected by
circulating triglyceride levels) should be
performed to conrm these results. How-
ever, a long follow-up is needed to docu -
ment effects on hard cardiovascular end
points, and conrmatory data are not
likely to be available for many years.
In conclusion, this is the rst prospec-
tive study showing that bariatric surgery is
associated with reduced incidence of myo-
cardial infarction in obese individuals with
type 2 diabetes. It also provides support for
the recommendations of the international
guidelines regarding bariatric surgery in
obese individuals with type 2 diabetes.
Acknowledgmentsd This study was sup-
ported by grants from the Swedish Research
Table 2dMultivariable Cox proportional hazards models for fatal plus nonfatal cardiovascular events in SOS subjects with
diabetes at baseline
CVE (63 + 65 ev ents) MI (38 + 43 events) Stroke (34 + 24 events)
HR (95% CI) P value HR (95% CI) P value HR (95% CI) P value
Surgery, yes/no 0.53 (0.350.79) 0.00 2 0.56 (0.340.93) 0.025 0.73 (0.411.30) 0.29
Male, yes/no 1.56 (0.972.52) 0.07 1.46 (0.792.69) 0.22 1.54 (0.773.07) 0.23
Age, per 6 .2 years 1.29 (1.051.60) 0.02 1.34 (1.021.77) 0.03 1.22 (0 .891.65) 0.21
Previous event, yes/no* 3.71 (2.036.79) ,0.001 4.49 (2.119.58) ,0.001 2.54 (0.5910.9) 0.21
Smoking, yes/no 2.46 (1.623.74) ,0.001 2.55 (1.514.30) ,0.001 1.95 (1.053.62) 0.03
BMI, per 4 .8 kg/m
2
1.16 (0.841.59) 0.35 1.09 (0.741.63) 0.65 1.09 (0 .691.74) 0.70
Waist, per 9.8 cm 0.94 (0.681.29) 0.71 0.99 (0.661.49) 0.96 0.95 (0 .591.54) 0.84
SBP, per 19.3 mmHg 1.34 (1.111.61) 0.00 2 1.38 (1.091.76) 0.008 1.37 (1.041.79) 0.02
Total cholesterol, per 46.9 mg/dL 1.54 (1.251.89) ,0.001 1.73 (1.332.24) ,0.001 1.14 (0.821.57) 0.44
HDL cholesterol, per 11.5 mg/dL 0.90 (0.711.14) 0.39 0.69 (0.500.94) 0.02 1.16 (0.841.59) 0.37
Triglycerides, per 200.9 mg/dL 0.85 (0.681.07) 0.17 0.78 (0.581.04) 0.08 0.99 (0.681.46) 0.99
Diabetes duration, per 4.9 years 1.36 (1.191.57) ,0.001 1.45 (1.231.72) ,0.001 1.27 (1.041.56) 0.02
Cox proportio nal hazards models based on baseline data were used to evaluate time to cardiovascular event (CVE). HRs were also adjusted for cardiovas cular disease
risk factors. Continuous traits HRs are expres sed per one-SD difference at base line in the population. Number of events is given in the headings for surgery + control
group. MI, myocardial infarction; SBP, systolic blood pressure. Including MI and stroke combined, whichever came rst. *Event indicates presence of previous CVE,
MI, and stroke.
2616 DIABETES CARE, VOLUME 35, DECEMBER 2012 care.diabetesjournals.org
Bariatric surgery, diabetes, and cardiovascular events
Page 4
Council (K2012-55X-22082-01-3, K2010-55X-
11285-13, and K2008-65x-20753-01-4), the
Swedish Foundation for Strategic Research to
Sahlgrenska Centre for Cardiovascular and
Metabolic Research, and the Swedish federal
government under the LUA/ALF agreement.
No potential conicts of interest relevant to
this article were reported.
S.R. designed and conducted the analyses,
interpreted the data, contributed to discus-
sion, and wrote, reviewed, and edited the
manuscript. C.M. performed the analyses, con-
tributed to discussion, and wrote and reviewed
the manuscript. M.A.B. performed the analyses,
contributed to discussion, and reviewed the
manuscript. C.P., K.S., P.J., and P.-A.S. contrib-
uted to discussion and reviewed the manuscript.
M.P. contributed to the analyses and reviewed
the manuscript. L.S. contributed to discussion
and wrote, reviewed, and edited the manuscript.
L.M.S.C. interpreted the data, contributed to
discussion, and wrote, reviewed, and edited the
manuscript. All the authors read and approved
the nal version of the manuscript. S.R. is the
guarantor of this work and, as such, had full ac-
cess to all the data in the study and takes re-
sponsibility for the integrity of the data and the
accuracy of the data analysis.
The authors thank the staff members at 480
primary health care centers and 25 surgical
department s in Sweden that participated in the
study. Gerd Bergmark, Christina Toref alk, and
Lisbeth Eriksson (Sahlgr enska Academy,
University of Gothenburg) are acknowledged
for invaluable administrative su pport.
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Romeo and Associates
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    • "In addition to the improvement in glycemic control, surgery significantly improved lipid profile. It is likely that this improvement may further contribute to the decreased cardiovascular disease risk associated with bariatric surgery [24,25]. The main disadvantages of this procedure that should be mentioned are the technically challenging nature of the procedure, risks of leaks, mesenteric internal hernias, future bowel obstruction, inability to assess the common bile duct, unknown long-term results, unknown revisions schemes, and unknown long-term nutritional deficiencies. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Bariatric surgery is an effective intervention for morbidly obese individuals, and it normalizes the level of glycemia in the majority of patients with type 2 diabetes mellitus (T2DM). Objectives: The primary aim of the study was to examine the efficacy of diverted sleeve gastrectomy with ileal transposition on weight loss and glycemic control in overweight, obese, and morbidly obese T2DM patients. The secondary aim was to examine the relationship between the effect of surgery and body mass index (BMI). Setting: Metabolic surgery clinic. Methods: This study was performed between October 2011 and August 2014, and mean duration of follow-up was 1 year. A total of 131 patients with T2DM were included. Ileal transposition with sleeve gastrectomy were performed in all patients. Each patient received a standard mixed meal tolerance test; plasma glucose, C-peptide, and insulin concentrations were measured before and 1 hour after the test. Postoperative alterations in BMI were noted. Results: Mean BMI decreased from 33.1±.5 to 23.5±.2 kg/m(2) at 1 year, with the magnitude of weight loss correlating with baseline weight (P<.0001). There were marked decreases in fasting plasma glucose concentration and mean glycosylated hemoglobin levels at 1 year. Neither the decrease in fasting plasma glucose or glycosylated hemoglobin correlated with the decrease in weight. The homeostasis model assessment index decreased from 9.6±1.2 to 2.2±.2, P<.0001, and the Matsuda index for insulin sensitivity increased from 2.2±.2 to 7.8±.4, P<.0001. Despite the improvement in insulin sensitivity, surgery caused a 4-fold increase in insulin secretion (P<.01). Conclusion: Diverted sleeve gastrectomy with ileal transposition is effective in glycemic control in patients with T2DM; however, this was not dependent on preoperative BMI values.
    Full-text · Article · Oct 2015 · Surgery for Obesity and Related Diseases
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    • "Several short-term studies have shown that weight reduction improves cardiovascular function [ Farb and Gokce: Adiposopathy and vascular function 131 surgery currently represents the most effective and durable weight loss intervention. It is also the sole weight reduction method shown to reduce long-term ( > 10 year) cardiovascular mortality, largely owning to decreased myocardial infarction risk [100, 121, 122]. Specific mechanisms for this improvement in cardiovascular health remains largely unclear, though recent data from the Swedish Obesity Study identified plasma insulin levels as the primary predictor of risk reduction [100]. "
    [Show abstract] [Hide abstract] ABSTRACT: Obesity has emerged as one of the most critical health care problems globally that is associated with the development of insulin resistance, type 2 diabetes mellitus, metabolic dysfunction and cardiovascular disease. Central adiposity with intra-abdominal deposition of visceral fat, in particular, has been closely linked to cardiometabolic consequences of obesity. Increasing epidemiological, clinical and experimental data suggest that both adipose tissue quantity and perturbations in its quality termed "adiposopathy" contribute to mechanisms of cardiometabolic disease. The current review discusses regional differences in adipose tissue characteristics and highlights profound abnormalities in vascular endothelial function and angiogenesis that are manifest within the visceral adipose tissue milieu of obese individuals. Clinical data demonstrate up-regulation of pro-inflammatory and pro-atherosclerotic mediators in dysfunctional adipose tissue that may support pathological vascular changes not only locally in fat but also in multiple organ systems, including coronary and peripheral circulations, potentially contributing to mechanisms of obesity-related cardiovascular disease.
    Full-text · Article · Feb 2015 · Hormone molecular biology and clinical investigation
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    • "In recent years, research demonstrated new evidence for cell cycle-dependent, rapamycin-resistant phosphorylation of ribosomal protein S6 at S240/244 (Rosner et al., 2010). Furthermore, RSK (90 kDa ribosomal S6 kinase) was found to contribute to rpS6 phosphorylation in response to agonists or oncogenes that activate the MAPK pathway (Romeo et al., 2012). Understanding the RSK-and S6K-specific phosphorylation events on S6 will be necessary to determine the complexities of S6 regulation and function. "
    [Show abstract] [Hide abstract] ABSTRACT: Ribosomal protein (rp) S6 is the substrate of ribosomal protein S6K (S6 kinase) and is involved in protein synthesis by mTOR/S6K/S6 signaling pathway. Some S6 cDNA have been cloned in mammals in recent years but has not been identified in the goat. To facilitate such studies, we cloned the cDNA encoding Cashmere goat (Capra hircus) S6 (GenBank accession GU131122) and then detected mRNA expression in seven tissues by real time PCR and protein expression in testis tissue by immunohistochemisty. Sequence analysis indicated that the obtained goat S6 was a 808 bp product, including a 3' untranslated region of 58 bp and an open reading frame of 750 bp which predicted a protein of 249 amino acids. The predicted amino acid sequence was highly homologous to cattle, human, mouse and rat S6. Expression analysis indicated S6 mRNA was expressed extensively in detected tissues and S6 protein was expressed in testis tissue.
    Full-text · Article · Nov 2013 · Asian Australasian Journal of Animal Sciences
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