Long-term Metabolic Effects of Laparoscopic Sleeve Gastrectomy

Abstract

The prevalence of laparoscopic sleeve gastrectomy (LSG) is increasing, but data on its long-term effect on obesity-related comorbidities are scarce. Because the population of bariatric patients is young, long-term results of those comorbidities are highly relevant.
To investigate the long-term effects of LSG on weight loss, diabetes mellitus, hypertension, dyslipidemia, and hyperuricemia.
Cohort study using a retrospective analysis of a prospective cohort at a university hospital. Data were collected from all patients undergoing LSGs performed by the same team between April 1, 2006, and February 28, 2013, including demographic details, weight follow-up, blood test results, and information on medications and comorbidities.
Excess weight loss, obesity-related comorbidities, and partial and complete remission at 1, 3, and 5 years of follow-up.
A total of 443 LSGs were performed. Complete data were available for 241 of the 443 patients (54.4%) at the 1-year follow-up, for 128 of 259 patients (49.4%) at the 3-year follow-up, and for 39 of 56 patients (69.6%) at the 5-year follow-up. The percentage of excess weight loss was 76.8%, 69.7%, and 56.1%, respectively. Complete remission of diabetes was maintained in 50.7%, 38.2%, and 20.0%, respectively, and remission of hypertension was maintained in 46.3%, 48.0%, and 45.5%, respectively. Changes in high-density lipoprotein cholesterol level (mean [SD] level preoperatively and at 1, 3, and 5 years, 46.7 [15.8], 52.8 [13.6], 56.8 [16.0], and 52.4 [13.8] mg/dL, respectively) and triglyceride level (mean [SD] level preoperatively and at 1, 3, and 5 years, 155.2 [86.1], 106.3 [45.3], 107.2 [53.4], and 126.4 [59.7] mg/dL, respectively) were significant compared with preoperative and postoperative measurements (P < .001). The decrease of low-density lipoprotein cholesterol level was significant only at 1 year (P = .04) and 3 years (P = .04) (mean [SD] level preoperatively and at 1, 3, and 5 years, 115.8 [33.2], 110.8 [32.0], 105.7 [25.9], and 110.6 [28.3] mg/dL, respectively). The changes in total cholesterol level did not reach statistical significance (mean [SD] level preoperatively and at 1, 3, and 5 years, 189.5 [38.2], 184.0 [35.4], 183.4 [31.2], and 188.1 [35.7] mg/dL, respectively). No changes in comorbidity status correlated with preoperative excess weight. Hypertriglyceridemia was the only comorbidity whose remission rates at 1 year of follow-up (partial/complete, 80.6%; complete, 72.2%) correlated with percentage of excess weight loss (76.8%) (P = .005).
Undergoing LSG induced efficient weight loss and a major improvement in obesity-related comorbidities, with mostly no correlation to percentage of excess weight loss. There was a significant weight regain and a decrease in remission rates of diabetes and, to a lesser extent, other comorbidities over time.

Full text

Copyright 2015 American Medical Association. All rights reserved.
Long-term Metabolic Effects of Laparoscopic
Sleeve Gastrectomy
Inbal Golomb, BSc; Matan Ben David, MD; Adi Glass, BSc; Tamara Kolitz, MD; Andrei Keidar, MD
IMPORTANCE The prevalence of laparoscopic sleeve gastrectomy (LSG) is increasing, but data
on its long-term effect on obesity-related comorbidities are scarce. Because the population of
bariatric patients is young, long-term results of those comorbidities are highly relevant.
OBJECTIVE To investigate the long-term effects of LSG on weight loss, diabetes mellitus,
hypertension, dyslipidemia, and hyperuricemia.
DESIGN, SETTING, AND PARTICIPANTS Cohort study using a retrospective analysis of a
prospective cohort at a university hospital. Data were collected from all patients undergoing
LSGs performed by the same team between April 1, 2006, and February 28, 2013, including
demographic details, weight follow-up, blood test results, and information on medications
and comorbidities.
MAIN OUTCOMES AND MEASURES Excess weight loss, obesity-related comorbidities, and
partial and complete remission at 1, 3, and 5 years of follow-up.
RESULTS A total of 443 LSGs were performed. Complete data were available for 241 of the
443 patients (54.4%) at the 1-year follow-up, for 128 of 259 patients (49.4%) at the 3-year
follow-up, and for 39 of 56 patients (69.6%) at the 5-year follow-up. The percentage of
excess weight loss was 76.8%, 69.7%, and 56.1%, respectively. Complete remission
of diabetes was maintained in 50.7%, 38.2%, and 20.0%, respectively, and remission of
hypertension was maintained in 46.3%, 48.0%, and 45.5%, respectively. Changes in
high-density lipoprotein cholesterol level (mean [SD] level preoperatively and at 1, 3, and 5
years, 46.7 [15.8], 52.8 [13.6], 56.8 [16.0], and 52.4 [13.8] mg/dL, respectively) and
triglyceride level (mean [SD] level preoperatively and at 1, 3, and 5 years, 155.2 [86.1], 106.3
[45.3], 107.2 [53.4], and 126.4 [59.7] mg/dL, respectively) were significant compared with
preoperative and postoperative measurements (P< .001). The decrease of low-density
lipoprotein cholesterol level was significant only at 1 year (P= .04) and 3 years (P= .04)
(mean [SD] level preoperatively and at 1, 3, and 5 years, 115.8 [33.2], 110.8 [32.0], 105.7 [25.9],
and 110.6 [28.3] mg/dL, respectively). The changes in total cholesterol level did not reach
statistical significance (mean [SD] level preoperatively and at 1, 3, and 5 years, 189.5 [38.2],
184.0 [35.4], 183.4 [31.2], and 188.1 [35.7] mg/dL, respectively). No changes in comorbidity
status correlated with preoperative excess weight. Hypertriglyceridemia was the only
comorbidity whose remission rates at 1 year of follow-up (partial/complete, 80.6%; complete,
72.2%) correlated with percentage of excess weight loss (76.8%) (P= .005).
CONCLUSIONS AND RELEVANCE Undergoing LSG induced efficient weight loss and a major
improvement in obesity-related comorbidities, with mostly no correlation to percentage of
excess weight loss. There was a significant weight regain and a decrease in remission rates of
diabetes and, to a lesser extent, other comorbidities over time.
JAMA Surg. 2015;150(11):1051-1057. doi:10.1001/jamasurg.2015.2202
Published online August 5, 2015.
Invited Commentary
page 1057
Author Affiliations: Bariatric Clinic,
Rabin Medical Center, Beilinson
Hospital, Petah Tikva, Israel (Golomb,
Glass, Keidar); Department of
Surgery, Rabin Medical Center,
Beilinson Hospital, Petah Tikva, Israel
(Ben David, Keidar); Department of
Internal Medicine, Rabin Medical
Center, Beilinson Hospital, Petah
Tikva, Israel (Kolitz).
Corresponding Author: Andrei
Keidar,MD, Bariatric Clinic, Rabin
Medical Center, Beilinson Hospital,
Petah Tikva 4959208,Israel
(keidar66@yahoo.com).
Research
Original Investigation
(Reprinted) 1051
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Obesity was recognized as a global epidemic by the World
Health Organization 15 years ago
1
and rates of obesity
have since been increasing. Obesity is currently con-
sidered a severe health hazard and a risk factor for diabetes melli-
tus, hypertension, dyslipidemia, heart failure, and many other
related comorbidities.
2
Obesity causes increased risk for car-
diovascular disease, even after eliminating other risk factors.
3
It is also a significant independent predictor of renal failure, in-
flammation, and many other comorbidities.
3-5
Bariatric procedures are reportedly the most effective strat-
egy to induce weight loss compared with nonsurgical
interventions.
6,7
Laparoscopic sleeve gastrectomy (LSG) is a
common and efficient bariatric procedure with increasing
popularity in the Westernworld during the last few years.
8
Both
intermediate and long-term data on LSGremain limited.
9
Most
of the earlier analyses had focused on weight loss and the re-
mission of diabetes,
6
even though hypertension, dyslipid-
emia, and hyperuricemia are also comorbidities commonly re-
lated to obesity. Moreover, most of the information on
dyslipidemia is based on records from follow-up of 2 years or
less,
10
and there are relatively few data on the long-term ef-
fects of LSG on these and other comorbidities.
In this study, we aimed to determine the effect of LSG on
diabetes, hypertension, hypercholesterolemia, hypertriglyc-
eridemia, and hyperuricemia after 1, 3, and 5 years. We also
sought to establish whether the remission of any of those obe-
sity-related comorbidities is correlated with weight loss and
which patients would be most likely to benefit from this pro-
cedure. The choice of bariatric procedure currently depends on
the surgeon’s preference, and there are few objective data to
compare the different approaches and their impact on spe-
cific comorbidities. This information is crucial to allow pa-
tients and physicians to choose the most appropriate proce-
dure according to the specific needs of each patient. The primary
end points of this study were excess weightloss and partial and
complete remission of obesity-related comorbidities.
Methods
This cohort study is a retrospective analysis of prospectively col-
lected data. Between April 1, 2006, and February 28, 2013, 1098
obese patients underwent bariatric surgery by the same surgical
team. Of these, 443 underwent LSG. All patientshad fulfilled the
criteria for undergoing bariatric surgery established by the
National Institutes of Health Consensus Conference.
11
They were
assigned to undergo an LSG based on clinical criteria, patient
choice, and the consensus of the bariatric clinic team. Potential
advantages, disadvantages, and risks of all procedures wereex-
plained in detail. The study was approved by the Rabin Medical
Center Institutional Review Board. Owing to the retrospective
nature of the study, a waiver of informed consent was granted.
Surgical Technique
All the LSGs were performed by the same surgical team. The gas-
tric tube was created using a 32Fr to 40Fr bougie. Stomach re-
section started 2 to 4 cm from the pylorus. Sleeve volume ranged
from 60 to 100 mL. Selective inversion of the staple line by se-
roserosal continuous suture (bougie in) was performed. Only the
areas of bleeding or staples crisscrossing or where the staples
seemed to not fit perfectly were oversutured.
The methylene blue dye leak test was used to ensure an
intact staple line. The percentage of excessweight loss (%EWL)
was calculated by assuming a normalized body weight at a body
mass index (BMI; calculated as weight in kilograms divided by
height in meters squared) of 25 and determined by dividing
the postoperative weightloss by the preoperative excess weight
and multiplying the result by 100.
Patient Care
Demographic data and the results of baseline blood tests were
collected. Type 2 diabetes mellitus (T2DM) was defined as a fast-
ing glucose level higher than 126 mg/dL (toconvert to millimoles
per liter, multiply by 0.0555) and glycated hemoglobin greater
than 6% of total hemoglobin (to convertto proportion of total he-
moglobin, multiply by 0.01), or any levelsin a patient receiving
antihyperglycemictreatment. Impaired fasting glucose (IFG) was
defined as a fasting glucose level higher than 100 mg/dL and
lower than 126 mg/dL in patientsw ith no use of antihyperglyce-
mic treatment. Hypercholesterolemiawas defined as a total cho-
lesterol level higher than 200 mg/dL (toconvert to millimoles per
liter, multiply by0.0259). Hypertriglyceridemia was defined as
a triglyceride level higher than 150 mg/dL (to convert to milli-
moles per liter, multiply by 0.0113). Hypertension was defined
as blood pressure higher than 140/90 mm Hgon more than 3 oc-
casions or the use of medications to treat hypertension. Hyper-
uricemia was defined as a plasma uric acid level higher than 6.8
mg/dL (to convert tomic romoles per liter, multiply by 59.485).
Preoperative and postoperativelaboratory assessments included
a complete blood cell count and ferritin, albumin, fasting glucose,
glycated hemoglobin, lipid profile, serum folate, vitamin B
12
,vi-
tamin D, and parathyroid hormone analyses. Information on
medication use was also collected prior to the surgery.
The postoperative follow-up was scheduled to take place
at 1, 3, 6, and 12 months and every year thereafter. Data were
gathered from hospital medical records, postoperative office
visit findings, and telephone interviews. Remissions of T2DM
and IFG were defined as a normal fasting glucose level (<100
mg/dL) and a normal glycated hemoglobin level (<6% of total
hemoglobin), respectively, with no use of insulin or oral medi-
cations. Partial remission for T2DM was defined as a reduc-
tion of medication dosage or cessation of medication use de-
spite abnormal laboratory results. No partial remission was
defined for IFG. Forarterial hypertension, normal blood pres-
sure without medication was considered remission and a de-
crease of medication dosage was considered partial remis-
sion. Remission of hyperlipidemia was defined as cessation of
medication use with normal laboratory results. Partial remis-
sion was defined as reduction of medication dosage or cessa-
tion of medication use despite abnormal laboratory results.
Statistical Analysis
The statistical analysis was performed using SAS version 9.4
statistical software (SAS Institute, Inc). Continuous variables
are presented as mean (standard deviation). Categorical vari-
ables are presented as number (percentage). The ttest was used
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to compare the value of continuous variables between study
groups, and the χ
2
test was used to compare categorical vari-
ables between study groups. The paired ttest was used to as-
sess changes in clinical measures for patients at differenttimes.
Statistical significance was reached at P< .05.
Results
Of the total of 1098 patients who underwent bariatric surgery
between April 1, 2006, and February 28, 2013, 443 under-
went LSG. Complete data were available for 241 of the 443pa-
tients (54.4%) at the 1-year follow-up, for 128 of 259 patients
(49.4%) at the 3-year follow-up, and for 39 of 56 patients
(69.6%) at the 5-year follow-up. The study patients’ mean (SD)
age was 42.2 (12.4) years (range, 13-72 years), and their rel-
evant characteristics are listed in Table 1.
Prior to undergoing the surgery, 82 patients had been diag-
nosed as having T2DM, 65 as having IFG, 110 as having hyper-
tension, 155 as having hypercholesterolemia, 109 as having hy-
pertriglyceridemia, and 55 as having hyperuricemia. The rates
of patients who had partial or complete remission at 1, 3, and 5
years of follow-upare shown in Table 2. The rates of patients who
stopped using medications for T2DM were 64.5% at 1 year of
follow-up, 48.3% at 3 years, and 55.5% at 5 years. In patients with
preoperative insulin use, ratesof cessation of medic ationuse were
drastically lower than in the general T2DM population: 36.8%,
9.1%, and 0.0%at 1, 3, and 5 years, respectively.Complete remis-
sion of diabetes was maintained in 50.7%,38. 2%, and 20.0%, re-
spectively, and remission of hypertension was maintained in
46.3%, 48.0%, and 45.5%, respectively.
Effect on Weight Loss
The mean (SD) preoperative excessweight was 51.2 (18.4) kg, and
the mean (SD) preoperative BMI was 43.9 (6.6). At1 year of follow-
up, the mean (SD) body weight was 81.4 (16.7)kg, the mean (SD)
BMI was 29.9 (5.1),and the %EWL was 76.8%. At 3 years of follow-
up, the mean (SD) body weight was 84.1 (17.2) kg, the mean BMI
was 30.8 (5.3), and the %EWL was 69.7%. At 5 years of follow-
up, the mean (SD) weight was 88.6(15.7) kg, the mean (SD) BMI
was 32.3 (5.1), and the %EWL was 56.1%.There was a signific ant
decrease in %EWL between patients with 1 and 3 years of follow-
up or patients with 1 and 5 years of follow-up(−4.8%, P= .007;
and −16.3%, P< .001, respectively). The decrease in %EWL be-
tween 3 and 5 years was not statistically significant (P= .07). The
failure rates, determined as the percentage of patients with a
%EWL less than 50%, were 13.3%, 21.1%, and 38.5% at 1, 3, and
5 years, respectively. There was no mortality, and the leak rates
were 1.3% and 3.1% in the primary and conversion procedures,
respectively. Eighteen patients underwent conversionto another
bariatric procedure and were excluded from follow-up follow-
ing the conversion.
Postoperative Changes in Lipid Profiles
The changes in the high-density lipoprotein (HDL) choles-
terol and triglyceride levels were significant compared with the
Table 1. Baseline PatientCharacteristics for Patients at Each Follow-up Period
Characteristic
Follow-up, y
1
(n = 241)
3
(n = 128)
5
(n = 39)
Age, mean (SD), y 42.9 (12.5) 41.5 (13.4) 44.5 (12.5)
Female, No. (%) 172 (71.4) 95 (74.2) 24 (61.5)
Weight, mean (SD), kg 119.4 (21.4) 118.2 (20.0) 117.5 (22.6)
Excess weight, mean (SD), kg 51.2 (18.4) 49.9 (16.3) 48.6 (18.3)
BMI, mean (SD) 41.9 (6.7) 43.4 (5.8) 42.6 (6.5)
Patients with previous bariatric surgery, No. (%) 26 (10.8) 9 (7.0) 4 (10.3)
Type 2 diabetes mellitus, No. (%) 71 (29.5) 34 (26.6) 10 (25.6)
Impaired fasting glucose, No. (%) 52 (21.6) 27 (21.1) 7 (17.9)
Hypertension, No. (%) 108 (44.8) 50 (39.1) 10 (25.6)
Hypercholesterolemia, No. (%) 153 (63.5) 68 (53.1) 21 (53.8)
Hypertriglyceridemia, No. (%) 106 (44.0) 53 (41.4) 18 (46.2)
Hyperuricemia, No. (%) 52 (21.6) 23 (18.0) 8 (20.5)
Abbreviation: BMI, body mass index
(calculated as weight in kilograms
divided by height in meters squared).
Table 2. Remission Rates at 1,3, and 5 Years of Follow-up
Comorbidity
Remission, %
1y 3y 5y
Partial/Complete Complete Partial/Complete Complete Partial/Complete Complete
Type 2 diabetes mellitus 93.2 50.7 91.2 38.2 80.0 20.0
Hypertension 77.8 46.3 80.0 48.0 54.5 45.5
Hypercholesterolemia 56.8 40.0 57.4 45.6 52.2 26.1
Hypertriglyceridemia 80.6 72.2 73.6 66.0 83.3 72.2
Hyperuricemia 76.9 71.2 82.6 73.9 100.0 87.5
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preoperative and postoperativemeasurements (P< .001). The
decrease of low-density lipoprotein (LDL) cholesterol levelwas
also significant at 1 year (P= .04) and 3 years (P= .04), but the
effect at 5 years did not reach statistical significance (P= .33).
Changes in total cholesterol levels failed to reach statistical sig-
nificance for any of the follow-up groups (Table 3). There was
no significant difference between the change of total choles-
terol, LDL cholesterol, HDL cholesterol, and triglyceride lev-
els in patients with 1 and 3 years of follow-upor in patients with
1and5yearsoffollow-up.
Relationship Between Changes in Comorbid Conditions,
Preoperative Characteristics, and Weight Loss
Correlations of changes in obesity-related comorbid conditions
with age and preoperative excessweight, sex, other comorbidi-
ties, and postoperative %EWL were analyzed by the ttest. Par-
tial and complete remission of hypertension at 1 year of follow-
up correlated with age (youngerpatients had a higher chance of
partial or complete remission; P= .004) and with preoperative
T2DM (P= .02) and hypertriglyceridemia (P= .04). Hypercho-
lesterolemia, hyperuricemia, age, sex, preoperative excess
weight, and %EWL did not show any significant effect on the
change of hypertension. Partial and complete remission of hy-
pertriglyceridemia at 1 year of follow-upcorrelated with preop-
erative T2DM (P= .03) and %EWL (P= .005). Partial or complete
remission of T2DM, hypercholesterolemia, and hyperuricemia
showed no correlations with age; sex; preoperativehypertension,
hypercholesterolemia, hypertriglyceridemia,or hyperuricemia;
or %EWL. The %EWL was not significantly related to preopera-
tive obesity-related comorbidities, age, sex, or excess weight.
Discussion
The increasing prevalence of obesity and the consensus that
bariatric procedures are the most effective methods of weight
loss have led to the spiraling growth of these procedures. In-
deed, they are among the most commonly performed gastro-
intestinal operations worldwide.
8
Initially LSG had been de-
scribed as part of the duodenal switch, but its success led to
the suggestion that it could be used as a single and definitive
procedure for morbid obesity. In 2012, the American Society
for Metabolic and Bariatric Surgery noted that several matched-
cohort, prospective, and case-control studies demonstrated
that LSG was equivalent to or exceeded Roux-en-Y gastric by-
pass (RYGB) surgery as well as laparoscopic adjustable gastric
bypass surgery in terms of weight loss outcomes and improve-
ments in a variety of obesity-relatedcomorbidities after a short-
term follow-up.
12
Some of the advantages of LSG include tech-
nical cost efficiency and easy learnability, lack of an intestinal
anastomosis, normal intestinal absorption, and pylorus
preservation.
13
Long-term follow-up data on the statusof those
comorbidities following LSG, however, are sparse.
14
Reports on long-term results of LSG usually focused on
weight loss. In 2004, Sjöström et al
15
reported a significant re-
gain of body weight after 2 and 10 years following bariatric op-
erations. Long-term %EWL reportedly varied widely (46%-
86%), with a decline at longer follow-ups.
16-24
Our findings
agree with those results. The %EWL in our study groups de-
creased from 76.8% at 1 year to 69.7% at 3 years and 56.1% at
5 years of follow-up. The difference in %EWL between1 and 3
years as well as between 1 and 5 years were statistically sig-
nificant, but the difference in %EWL between 3 and 5 years was
not. This might imply that a major part of the weight regain
occurs in the first few years following the surgery. Further-
more, the failure rate, defined as the percentage of patientsw ith
a %EWL less than 50%, increased from 13.3% at 1 year of fol-
low-up to 21.1% at 3 years and 38.5% at 5 years.
The success of bariatric surgery is usually defined by long-
term weight loss, enduring improvement in comorbidities, and
low mortality and morbidity rates.
25
Rather than being consid-
ered a priority, the effect of those procedures on obesity-related
comorbidities is usually not taken into consideration when ana-
lyzing the results. Because the mean age of patients undergoing
bariatric surgery is usually 40 to 50 years, long-term results of
those comorbidities are both attainable and highly relevant.
Vest et al
26
performed a meta-analysis of different types
of bariatric surgery and cardiovascular outcomes. Ten of the
73 articles they reviewed included information on LSG, and the
length of follow-up rangedfrom 3 months to 14.5 years (mean,
4.8 years). The rates of partial or complete remission were73%
for diabetes, 63% for hypertension, and 73% for hyperlipid-
emia. Gill et al
27
systematically reviewed the effect of sleeve
gastrectomy on diabetes mellitus and reported that the com-
plete and partial remission rates at 13 months of follow-up were
66% and 27%, respectively. Sarkhosh et al
28
reviewed the ef-
fect of LSG on hypertension and found that 58% of patients
showed remission at a mean of 17 months. The effect of LSG
on hyperlipidemia was recently reviewed by Al Khalifa et al,
10
who reported that the partial and complete remission rate at
17 months was 83.5% and that the mean (SD) preoperative and
postoperative cholesterol levelswere 194.4 (12.3) mg/dL (range,
178-213 mg/dL) and 181 (16.3) mg/dL (range, 158-200 mg/dL),
respectively.
Table 3. Changesin Lipoprotein Prof ile
Measure
Mean (SD)
Preoperative
Follow-up, y
135
Cholesterol, mg/dL
Total 189.5 (38.2) 184.0 (35.4) 183.4 (31.2) 188.1 (35.7)
HDL 46.7 (15.8) 52.8 (13.6) 56.8 (16.0) 52.4 (13.8)
LDL 115.8 (33.2) 110.8 (32.0) 105.7 (25.9) 110.6 (28.3)
Triglycerides, mg/dL 155.2 (86.1) 106.3 (45.3) 107.2 (53.4) 126.4 (59.7)
Abbreviations: HDL, high-density
lipoprotein; LDL, low-density
lipoprotein.
SI conversion factors: Toconvert
total, HDL, and LDL cholesterol to
millimoles per liter, multiply by
0.0259; to convert triglycerides to
millimoles per liter, multiply by
0.0113.
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Reports on partial and complete remission of obesity-
related comorbidities after 3 or more yearsof follow-up after LSG
are scarce. In a systematic review by Brethauer et al,
29
only 1 of
the 10 studies on postoperative comorbidity statushad data from
follow-up longerthan 2 4 months.The range of partial and com-
plete remission is quite wide in the studies on the effect of sur-
gery on such comorbidities with a longer follow-up. In their
randomized trial, Schauer et al
30
compared the remission rates
of T2DM after LSG, RYGB, and medical therapy at 3 years of fol-
low-up and found that 24%of the patients who underwent LSG
had complete remission compared with 38% who underwent
RYBGand 5% who under wentmedic al therapy. Atkins et al
31
de-
scribed remission rates of 74.5%, 49.5%, and 26.5% for T2DM,
hypertension, and hyperlipidemia, respectively, at 4 years of fol-
low-up. Other studies with medium-term follow-up reported re-
mission rates of 67% to 86% for T2DM, hypertension, and
hyperlipidemia.
32-34
Our complete remission rates were lower:
38.2% for T2DM, 48.0% for hypertension, 45.6% for hypercho-
lesterolemia, and 66.0% for hypertriglyceridemia at 3 years of
follow-up. Lower remission ratescould be attributed to stricter
criteria, definition of remission, and interpretation of the labo-
ratory results. Studies also use different end points, making it
difficult to compare data. The definition of remission is espe-
cially important in the current context. A consensus statement
of the American Diabetes Association defined complete remis-
sion of diabetes as normal glycemic measures without the use
of pharmacologic therapy for 1 year or longer.
35
In this study,
however,we defined remission as normal postoperative glyce-
mic measures without medications, as reported in several other
studies.
36,37
One major additional drawback is the definition of
the term partial remission. Some studies define it as the reduc-
tion of medication, some as reduced severity of associated symp-
toms, and some as the normalization of laboratory results.
Clearly, different definitions cause vagueness of data. In this
study, we defined partial remission as the reduction of medi-
cation dosage or the cessation of medication use despite ab-
normal laboratory results. Moreover, our study showed that
64.5% of patients with preoperative use of antidiabetics stopped
using medications after 1 year of follow-up, with the rates at
3 and 5 years decreasing to 48.3% and 55.5%, respectively.
The majority of the patients with preoperative insulin use
did not require insulin treatment postoperatively: 63.2%
and 54.5% of patients stopped using insulin or were treatedw ith
oral diabetic agents only at 1 and 3 years of follow-up, respec-
tively. These results are lower than the rates of reduction of
insulin and oral diabetic agents reported by Schauer et al
38
fol-
lowing RYGB.
Complete remission rates in patients with preoperativein-
sulin use were much lower than complete remission rates in
the general T2DM population. This demonstrates the effect of
preoperative characteristics on remission rates. It is well known
that the severity of diabetes prior to surgery affects the remis-
sion rates. Therefore, diabetic patients with a long-standing
disease who are referred to the bariatric clinic as a last resort
cannot be compared with patients who undergo surgery shortly
after being diagnosed as having diabetes. As such, the differ-
ences between the reported remission rates may reflect the dif-
ferences in the levels of awareness of diabetologists.
The influence of LSG on hyperlipidemia warrants special
attention. Hyperlipidemia comprises 4 variables: total choles-
terol, LDL cholesterol, HDL cholesterol, and triglycerides. In
a recent analysis of changes in lipid profile in patientsafter LSG,
Zhang et al
39
noted that only HDL cholesterol and triglycer-
ide levels changed significantly. We also observed a signifi-
cant change in LDL cholesterol, HDL cholesterol, and triglyc-
eride levels, but the change in total cholesterol level did not
reach statistical significance. In addition, there was no signifi-
cant difference between the changes in the different fol-
low-up points, which means that the improvement in HDL cho-
lesterol and triglyceride levels did not deteriorate significantly
over time. A confounding factor of these results could be the
cessation of use of antihyperlipidemic agents.
Many authors have focused their studies on the compari-
son of different bariatric procedures. In a recent meta-
analysis, RYGB and LSG were found to have an equivalent ef-
fect on hypertension and dyslipidemia, although RYGB was
found to achieve better control of T2DM.
40
It should be noted
that most studies included in that meta-analysis reported data
that were retrieved after a follow-up of 2 years or less. Schauer
et al
30
also found RYGB to be superior to LSG in terms of the
likelihood of achieving a glycated hemoglobin level of 7% of
total hemoglobin or less with no use of diabetes medications
after 3 years of follow-up. Another study that compared the
improvement of the lipid profile followingLSG and RYGB found
that RYGB had a clear benefit in all lipid fractions.
41
Surprisingly, our results showed that none of the changes in
obesity-relatedcomorbidity status correlated with excess weight
prior to the surgery. Patients with preoperative T2DM were less
likely to show a remission of hypertension and hypertriglyceri-
demia. As described by others,
27
age was a negative predictive
factor for partial or complete remission of hypertension in our
study.Partial and complete remission of hypertension also cor-
related with preoperative hypertriglyceridemia.Hypertriglyceri-
demia was the only comorbidity whose remission rates correlated
with %EWL. Finally,there was a decline in the rates of remission
of diabetes at 1, 3, and 5 years of follow-up.
In our opinion, the presence of obesity-related comorbidi-
ties should play a major role when choosing the appropriatepro-
cedure for a specific patient. Forexample, performing an opera-
tion that yields a low resolution rate of hyperlipidemia translates
into lifelong medical treatment in a young patient with signifi-
cant hyperlipidemia. In that case, a malabsorptive procedure
might be more beneficial than an LSG procedure. If the recurrence
of obesity is known to be followed by the remittanceof an exist-
ing comorbidity in a specific procedure, an alternative procedure
should be considered. Forexample, the weight loss durability fail-
ure of almost 40% at 5 years of follow-up of the LSG should be
one of the deciding factors in such cases.
Our study has several limitations. First, patients lost to fol-
low-up may cause a bias because their characteristics and rea-
sons for not arriving at follow-up visits are unknown. How-
ever, the follow-up rates in this study are comparable to those
in other long-term studies
42
and our data included all pa-
tients’ relevant laboratory results. Another limitation is that
the follow-up was not continuous for all patientsand some fol-
low-up data were available for only 1 time. Also, the small
Metabolic Effects of Laparoscopic Sleeve Gastrectomy Original Investigation Research
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sample size at 5 years of follow-up precludes arriving at firm
conclusions regarding the changes in their obesity-related co-
morbidities.
Conclusions
The results of this analysis demonstrated that %EWL
decreased with longer follow-up. Furthermore, partial and
complete remission rates of T2DM were significantly lower
when follow-up was longer. Undergoing LSG induced a
reduction in %EWL and a major improvement in obesity-
related comorbidities in the short-term. The longer follow-up
data revealed weight regain and a decrease in remission rates
for T2DM and other obesity-related comorbidities. These
data should be taken into consideration in the decision-
making process for the most appropriate operation for a
given obese patient.
ARTICLE INFORMATION
Accepted for Publication: April 16, 2015.
Published Online: August 5, 2015.
doi:10.1001/jamasurg.2015.2202.
Author Contributions: Dr Keidar had full access to
all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
data analysis.
Study concept and design: Golomb, Ben David,
Keidar.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: Golomb, Glass, Kolitz,
Keidar.
Critical revision of the manuscript for important
intellectual content: Ben David, Kolitz,Keidar.
Statistical analysis: Golomb.
Administrative, technical, or material support: All
authors.
Study supervision: Ben David, Kolitz, Keidar.
Conflict of Interest Disclosures: None reported.
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Invited Commentary
No Rush to Judgment for Bariatric Surgery
Anita P. Courcoulas, MD, MPH
It is unclear whether current studies will address critical ques-
tions about the long-term outcomes of bariatric surgery, in-
cluding the sustainability of weight loss and comorbidity con-
trol and long-term complication rates.
1
These critical gaps in
knowledge pose a significant
problem for people consider-
ing a potential surgical op-
tion to treat severe obesity.
Contributing to these deficits are the paucity of comparative
trials, incomplete follow-up, a lack of standardized defini-
tions for changes in health status (eg, diabetes mellitus remis-
sion), and the tendency to a rush to judgment in favor of sur-
gical treatment options.
Laparoscopic sleeve gastrectomy is a good case in point,
evolving very quickly during the last several years into the
dominant procedure in use
2
despite a complete void of infor-
mation about the longer-term effects. Golomb et al
3
trytoad-
dress this by documenting 1-, 3-, and 5-year results in a co-
hort of 443 sleeve gastrectomy cases but clearly raise more
issues than they can answer. They show that both weight loss
and type 2 diabetes remission degrade substantially over time:
excess weight loss from 77% to 56% and complete remission
of diabetes from 51% to 20% between 1 and 5 years. Those re-
sults are from only 56 people available for 5-year followup and
with rates of loss to follow-up of 50%, on average, at 1 and 3
years. One must assume that people lost to follow-upmay dif-
fer in important ways. In addition, there are no standards to
report comorbid health changes following bariatric surgery,
which limits the ability to compare results across studies.
Golomb and colleagues do an excellent job of outlining the
study’s own specific definitions of prevalence, incidence, and
remission of type 2 diabetes and other health outcomes, but
these are neither standard nor shared between members of the
research community.
How can these problems be addressed? Large, prospec-
tive observational studies such as the Longitudinal Assess-
ment of Bariatric Surgery Consortium study report standard-
ized definitions and do better with long-term retention,
4
but
the burden of work and subsequent high cost are problematic
in a highly competitive funding environment.The issues of cost
and feasibility also make a large randomized trial that could
compare surgical procedures across heterogeneous popula-
tions impractical. There is hope for the use of large electronic
databases to contribute to these knowledge gaps, but the han-
dling of large amounts of missing data is a critical feature that
is often not well articulated by the authors or well under-
stood by the readers. The answers will likely be generated over
time not only by a few of these large-scale efforts but also by
thoughtful inference that will be made through pooled analy-
ses of data like that from Golomb and colleagues and from
many other disparate randomized and nonrandomized stud-
ies of bariatric surgery.
5
It will take time, patience, and a will-
ingness to avoid a rush to judgment. In the meantime, clini-
cians and prospective patients will need to discuss and weigh
the evidence in a dynamic exchange driven not always by
final conclusions but by the most current available data.
ARTICLE INFORMATION
Author Affiliation: Department of Surgery,
University of Pittsburgh Medical Center,Pittsburgh,
Pennsylvania.
Corresponding Author: Anita P. Courcoulas, MD,
MPH, Department of Surgery, University of
Pittsburgh Medical Center, 3380 Blvdof the Allie s,
Ste 390, Pittsburgh, PA 15213 (courcoulasap@upmc
.edu).
Published Online: August 5, 2015.
doi:10.1001/jamasurg.2015.2222.
Conflict of Interest Disclosures: Dr Courcoulas
reported receiving grants from Nutrisystem,
Ethicon, and Covidien and serving as a project
consultant for Ethicon and Apollo Endosurgery.
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