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Advances in Surgery 51 (2017) 29–40
ADVANCES IN SURGERY
Sleeve Gastrectomy and

Diabetes: Is Cure Possible?
Amin Andalib, MD, MSca, Ali Aminian, MDb,*
a
Department of Surgery, Montreal General Hospital, McGill University, 1650 Cedar Avenue,
Room E16-152, Montreal, Quebec H3G 1A4, Canada; bBariatric and Metabolic Institute,
Department of General Surgery, Cleveland Clinic, 9500 Euclid Avenue, M61, Cleveland, OH
44195, USA
Keywords
Sleeve gastrectomy Bariatric Diabetes Metabolic Remission Cure
Weight loss
Key points
Sleeve gastrectomy is the most commonly performed bariatric procedure in North
America.
Sleeve gastrectomy is shown to be highly effective in treating diabetes at
medium-term follow-up. Outcomes are comparable to those after gastric bypass.
Continued diabetes remission after sleeve gastrectomy decreases as follow-up
time increases. Long-term relapse of diabetes is reported to be 30% to 50%.
Nearly 75% of patients achieve long-term improvement to complete remission of
their diabetes after sleeve gastrectomy but cure remains infrequent, which sup-
ports performing surgery earlier on in the course of diabetes.
Precise antidiabetic mechanisms of sleeve gastrectomy are not well understood;
weight-independent neurohormonal pathways involving changes to gut hor-
mones, bile acids, and microbiota are all implicated.
B
ariatric-metabolic surgery is the cornerstone of definitive treatment of se-
vere obesity and related comorbidities [1]. Worldwide, sleeve gastrec-
tomy (SG) has become the most commonly performed bariatric and
metabolic procedure [2]. Despite the rising trend over the past decade, the ques-
tion of whether the resolution of comorbidities, especially type 2 diabetes
Disclosure Statement: The authors have nothing to disclose.
*Corresponding author. E-mail address: aminiaa@ccf.org
http://dx.doi.org/10.1016/j.yasu.2017.03.003
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30 ANDALIB & AMINIAN
mellitus (T2D) after SG, is as profound and durable as that of gastrointestinal

bypass procedures still remains.
DIABETES BURDEN
According to estimates from the International Diabetes Federation (IDF), 285
million adults suffered from diabetes in 2010 worldwide, a figure that is set
to increase to 438 million by 2030 [3]. In 2012, the estimated economic cost
of diabetes had increased by more than 40% in less than a decade and was
found to be $245 billion [4]. This estimate clearly underlines the significant so-
cietal burden of diabetes and is likely an underestimation that does not consider
indirect costs.
Obesity is also a global epidemic and by 2025, if current trends continue,
global obesity prevalence will rise to 18% [5]. Furthermore, obesity is strongly
associated with diabetes, along with several other major conditions [6]. Patients
with body mass index (BMI) greater than 35 kg/m2 have a 40-fold increased
risk of developing T2D than people with a normal BMI [7]. Nearly one-third
of patients undergoing bariatric surgery are known to have T2D [8].
Bariatric surgery, which has evolved into metabolic surgery, is the most
effective long-term treatment for obesity [9]. There is now also extensive clin-
ical and mechanistic evidence in favor of bariatric-metabolic surgery as an anti-
diabetes treatment of obese people with T2D and is formally endorsed by 45
international societies, including the American Diabetes Association (ADA)
and the IDF [10].
SLEEVE GASTRECTOMY
In 2003, Regan and colleagues [11] reported a 2-stage approach to the surgical
management of the high-risk patients with extreme obesity (BMI 60 kg/m2)
using SG as the initial procedure. Simplicity, safety, and outcomes of SG as
a stand-alone operation, coupled with dissatisfaction from adjustable gastric
banding, has turned it into the predominant bariatric procedure in North
America [2,12,13].
Laparoscopic SG achieves restriction via a tabularized stomach after near
80% of stomach is removed (Fig. 1) [14]. Resection starts within 3 to 6 cm of
the pylorus along the greater curvature of stomach and ends with removal
of the fundus calibrated using a bougie (size 32–60 French [Fr]).
Safety and postoperative morbidity

Laparoscopic SG is considered to be very safe with a 30-day mortality and
composite morbidity of 0.05% and 2.4%, respectively [15]. In a large nation-
wide study, SG was also found to be safe in overweight and class I obese pa-
tients with T2D [16]. Another recent large study on the Metabolic and
Bariatric Surgery Accreditation and Quality Improvement Program registry
analyzed the impact of different surgical techniques on outcomes of SG [17].
Two of the most troubling postoperative complications are postoperative
staple-line leaks (0.6%–1%) and hemorrhage (0.7%–1.4%) [15,17,18]. Bougie
SLEEVE GASTRECTOMY AND DIABETES 31
Fig. 1. Schematic diagram of SG. (Courtesy of Cleveland Clinic Center for Medical Art &
Photography, Cleveland Clinic, Cleveland, Ohio; with permission.)
size 38 Fr or greater was associated with lower leaks, and staple-line reinforce-
ment was found to be associated with lower postoperative bleeding requiring
transfusion, readmission, or reoperation [17].
Other rare perioperative complications pertinent to the patients with severe
diabetes undergoing SG, such as diabetic ketoacidosis and hypoglycemia, are
also reported and must be taken into consideration for prompt initiation of
therapy [19,20].
Long-term weight loss

Despite SG evolving into the most prominent stand-alone procedure over the
course of the past decade, the long-term data on postoperative clinical out-
comes are still rare. Himpens and colleagues [21] reported 57% excess weight
loss (EWL) at 6 years after SG in a cohort of 30 subjects. In a larger cohort, Eid
and colleagues [22] have reported a 48% EWL at a mean follow-up time of
more than 6 years, with an excellent retention rate of 93%. Moreover, in a
recent study of 134 diabetic subjects following SG, at a median follow-up of
6 years there was a 43% EWL, corresponding to 8 kg/m2 mean reduction in
BMI [23].
Although more long-term studies are needed, the approximate long-term
EWL of 40% to 60%, or a mean BMI reduction of 8 to 10 kg/m2 after SG, are
likely realistic estimates [21–24]. Heterogeneity of studies in terms of technical de-
tails, including bougie size and resection of gastric antrum, along with various
follow-up time and rate, can significantly affect the reported weight loss estimates.
Furthermore, as is the case for all weight loss procedures, SG is subject to long-
term weight regain in some patients primarily due to compensatory behavioral
and physiologic adaptations, and less likely due to surgical causes such as a large
sleeve or retained fundus. The marked suppression of ghrelin (appetite hormone)
after SG, among several proposed mechanisms of weight loss after SG, can disap-
pear long-term. Compensatory ghrelin secretion from the dilated stomach or
from extragastric ghrelin-producing glands can possibly explain long-term loss
of the appetite suppression effect of SG in some patients [21,25].
Long-term weight loss after SG may be less than other bypass-type proced-
ures. A recent meta-analysis comparing medium (3–5 years) and long-term
(5 years) postoperative outcomes between gastric bypass and SG demon-
strated that, although the medium-term weight loss is comparable between
the 2 procedures, SG has significantly lower weight loss after 5 years compared
with gastric bypass [26].
SLEEVE GASTRECTOMY AND TYPE 2 DIABETES

Short-term glycemic outcomes
At short-term follow-up and similar to gastric bypass, SG has repeatedly been
shown to be highly effective in the treatment of T2D [9,27,28]. In the Laparoscopic
Gastric Bypass versus Sleeve Gastrectomy to Treat Morbid Obesity (SLEEVE-
PASS) trial, SG resulted in 84% resolution or improvement of T2D at 6 months
after surgery, although the study did not use a widely accepted definition for dia-
betes remission [27]. The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS)
trial has shown similar results at 1 year postoperatively [29]. The Surgical Therapy
and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial
demonstrated that 37% subjects achieved glycated hemoglobin A1c
(HbA1c) lower than 6% and 27% were in complete remission with HbA1c lower
than 6% and without any use of diabetes medication 1 year after surgery [28].
SG has also been shown to be very effective in treatment of T2D at
medium-term follow-up with resolution rates of 20% to 70% at 3 years after
surgery [30–32]. However, the rate of persisting resolution of T2D decreases
as follow-up time increases. Results from the STAMPEDE trial revealed that
3 years after SG, 24% of subjects had HbA1c lower than 6%, whereas 20%
continued to be in remission with HbA1c lower than 6% and without any
use of diabetes medication [31].
Long-term glycemic outcomes

The 5-year outcomes from the SLEEVEPASS [27], and SM-BOSS [29] trials are
still not reported. Recently, the STAMPEDE trial revealed that 5 years after
SG, 23% of subjects had HbA1c lower than 6%, whereas 15% continued to
be in remission with HbA1c lower than 6% and without any use of diabetes
medication [33]. Other studies reporting long-term glycemic outcomes in dia-
betic patients after SG are scarce and limited to small case series [22,34–39].
Also recently, in the largest series yet, the outcomes of SG in subjects with
T2D with at least 5 years of follow-up are reported [23]. In a cohort of 134
diabetic subjects following SG (87% follow-up rate), it was found that after
5 years T2D was improved in 73% of subjects and ADA glycemic goals
were achieved in nearly two-thirds [23]. Although complete remission
(HbA1c <6% and no diabetes medications) was obtained in 11%, cure, defined
as continuous complete remission for 5 years after surgery [40], was achieved
in only 3% of the cohort (Figs. 2 and 3) [23].
Despite the short-term to medium-term effectiveness, results from recent
studies indicate a late relapse rate of 30% to 50% in subjects with T2D after
bariatric surgery [23,31,41]. Reported relapse rates vary depending on the defi-
nition of relapse, subject population, type of surgery performed, and length and
completeness of follow-up. The risk factors for T2D relapse, particularly after
SG, are not well described. Older age, longer course of T2D, worse preopera-
tive glycemic control, 2 or more diabetic medications at baseline, insulin-
dependence, and weight regain after surgery have been linked to relapse of dia-
betes after bariatric surgery [23,31,42,43]. Nonetheless, relapse of T2D years
after bariatric surgery should not be viewed as a failure because the trajectory
of metabolic and cardiovascular risk factors is significantly improved by sur-
gery [23]. Furthermore, large diabetes trials have demonstrated a phenomenon
called metabolic memory or legacy effect after a transient period of aggressive
glycemic control. Long-term follow-up of subjects after the trials ended showed
a reduction in incidence of end-organ complications of T2D, even when the
tight control relented [44–46]. In a similar way, patients after SG may experi-
ence a sustained long-term benefit from this metabolic memory phenomenon.
Fig. 2. Long-term changes in BMI and glycated HbA1c after sleeve gastrectomy. D:
Mean SD at the last follow-up point—baseline at time of surgery. (Adapted from Aminian
A, Brethauer SA, Andalib A, et al. Can sleeve gastrectomy cure diabetes? Long-term metabolic
effects of sleeve gastrectomy in patients with type 2 diabetes. Ann Surg 2016;264(4):676;
with permission.)
Fig. 3. Short-term and long-term diabetes remission rates and late relapse rate after initial post-
surgical remission (left), meeting the ADA glycemic goal HbA1c <7% (middle), and long-term
remission rates (complete and partial) of diabetes based on various baseline predictive factors
(right) following sleeve gastrectomy. (Adapted from Aminian A, Brethauer SA, Andalib A,
et al. Can sleeve gastrectomy cure diabetes? Long-term metabolic effects of sleeve gastrectomy
in patients with type 2 diabetes. Ann Surg 2016;264(4):677; with permission.)
Predictors of long-term diabetes remission

Higher weight loss after SG, and a combination of shorter duration of diabetes
(5 years) and taking 2 or fewer diabetes medications have been found as impor-
tant predictors of long-term remission of T2D [23,43]. These observations are likely
attributed to the patients improved lifestyle habits and a surrogate for the presence
of more functional ß-cell reserve, suggesting that an earlier metabolic surgery in pa-
tients with T2D is likely more successful in achieving remission [23,43,47]. The
importance of an earlier metabolic surgery in the course of T2D on long-term dia-
betes remission has also been shown after gastric bypass [42,43,48].
Multiple prediction models for T2D remission after gastric bypass surgery
have been reported but only 2 (DiaRem score [48] and ABCD score [49]) have
been externally validated [50]. Unfortunately, none of these models are derived
based on prediction of T2D remission at long-term. ABCD score is the only pre-
diction model that has been tested on SG patients [51]. Four baseline categorical
variables, including BMI, C-peptide level, duration of T2D, and age, are used to
calculate the ABCD score and predict remission of T2D [49,51]. These predictors
underscore the importance of an earlier surgical intervention at a time with higher
ß-cell reserve to increase the likelihood of curing T2D.
Comparison with medical treatment

Superiority of bariatric surgery over intensive lifestyle and medical therapy has
been shown repeatedly in several high-quality randomized control trials
[33,52,53]. Only the STAMPEDE trial has officially compared the outcomes
of SG with intensive medical therapy [33]. Five years after surgery, SG is found
to be far superior than intensive medical therapy for improving glycemic
control (23% vs 5% HbA1c <6%, respectively), other cardiovascular risk fac-

tors, and quality of life of patients (Fig. 4) [33].
The clear advantage of bariatric surgery over medical or lifestyle interven-
tions has led to the formal endorsement of metabolic surgery, including SG,
as a treatment for T2D in obese patients by important international societies,
including the ADA and the IDF [10].
Comparison with other bariatric procedures
In a meta-analysis of 33 studies, including randomized control trials, prospec-
tive, and retrospective studies, Yip and colleagues [54] reported no significant
difference in T2D remission at 3 years between SG and gastric bypass (80%
vs 81%). In another meta-analysis, gastric bypass was found to be more effec-
tive in resolution of T2D compared with SG at 5-year follow-up [55]. However,
both these meta-analyses have pooled data from significantly heterogeneous
studies using different HbA1c thresholds and definitions for T2D remission.
Although there are multiple ongoing randomized controlled trials
comparing outcomes of SG with gastric bypass [27,29] only one has published
long-term outcomes for 5 or more years [33]. In the STAMPEDE trial, 5 years
after surgery, 23% subjects had HbA1c lower than 6% following SG
compared with 29% after gastric bypass; moreover, 15% continued to be in
remission with HbA1c lower than 6% and without any diabetes medications
after SG versus 22% after gastric bypass [33]. Neither of these differences was
found to be statistically significant, although the trial was not adequately pow-
ered to detect modest differences between these procedures. The percentage
of patients who were not taking any diabetes medications was significantly
higher in the gastric bypass group than in the sleeve gastrectomy group.
Fig. 4. The percentage change in glycated hemoglobin levels during the study period over a
5-year period among subjects receiving intensive medical therapy only, sleeve gastrectomy, or
gastric bypass in the STAMPEDE trial. (Adapted from Schauer PR, Bhatt DL, Kirwan JP, et al.
Bariatric surgery versus intensive medical therapy for diabetes–5-year outcomes. N Engl J
Med 2017;376(7):646; with permission.)
ANTIDIABETIC MECHANISM OF ACTION

The precise antidiabetic mechanisms after SG are not well described. Weight
loss and caloric restriction have been shown to improve glycemic control
[56]. It seems that improvement in glucose homeostasis is also achieved by
weight-independent mechanisms [25,56,57]. SG is shown to modify gut hor-
mone levels, such as ghrelin, peptide YY, and glucagon-like peptide (GLP)-1,
similar to bypass-type bariatric procedures [25,42,58,59]. Long-term remission
of T2D after SG has been shown to be associated with an elevated postprandial
GLP-1 response [42]. Circulating bile acids are also shown to be vital regulators
of energy balance, mainly via modulating farnesoid X receptors, and are
clearly increased after SG. They also affect the gut microbiome by changing
it into a leaner bacterial flora [56,60,61]. An overview of the proposed antidia-
betic mechanisms of action after SG is shown in Fig. 5.
SLEEVE GASTRECTOMY AND TYPE 1 DIABETES

The body of literature evaluating the impact of bariatric surgery on patients
with type 1 diabetes mellitus (T1D) is scarce. The evidence on the effect of
SG on T1D is even more limited. In a recent review of 17 studies that included
more than 100 obese patients with T1D, it was shown that bariatric surgery
significantly improves the glycemic control in these patients, reduces weight-
Fig. 5. Proposed mechanisms of action of sleeve gastrectomy in obese patients with type 2
diabetes. IL-6, interleukin-6; TG, triglycerides; TNF, tumor necrosis factor. (Adapted from Kir-
wan JP, Aminian A, Kashyap SR, et al. Bariatric surgery in obese patients with type 1 diabetes.
Diabetes Care 2016;39(6):945; with permission.)
adjusted daily doses of insulin, and decreases HbA1c [62]. Because SG is asso-
ciated with more predictable absorption of carbohydrates and fat-soluble nutri-
ents compared with diversionary procedures, it might be a reasonable surgical
option in patients with T1D who are at risk for development of postoperative
hypoglycemia [62,63]. Attention must be given to certain adverse events in the
early postoperative period, such as diabetic ketoacidosis, hypoglycemia, and
gastrointestinal dysmotility symptoms (prolonged ileus and acute gastric
remnant dilation) [20,62,64].
SUMMARY
SG is the most commonly performed metabolic procedure in North America.
In addition to being an efficient weight loss procedure, SG is very effective
in improving cardiometabolic risk factors, including glycemic state up to
medium-term follow-up. Studies on long-term outcomes of SG, especially
regarding treatment of T2D, are rare. Long-term complete remission and
cure of T2D after SG is not common, especially in patients with prolonged
and poorly controlled diabetes. Hence, SG in early stages of T2D would
more likely lead to sustained improved glycemic outcomes. Because late relapse
of T2D is frequent, continued monitoring of glycemic status is highly recom-
mended. Better predictive models for long-term diabetes remission using base-
line characteristics are also needed to better guide timing and type of metabolic
surgery. In addition, more high-quality studies evaluating long-term antidia-
betic effects of SG, especially with regard to impact on end-organ dysfunction
such as nephropathy, retinopathy, cardiovascular outcomes, overall survival,
and quality of life, are warranted.
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Advances in Surgery 51 (2017) 29–40

Sleeve Gastrectomy and

Disclosure Statement: The authors have nothing to disclose.

*Corresponding author. E-mail address: aminiaa@ccf.org

mellitus (T2D) after SG, is as profound and durable as that of gastrointestinal

Safety and postoperative morbidity

Long-term weight loss

SLEEVE GASTRECTOMY AND TYPE 2 DIABETES

Long-term glycemic outcomes

Predictors of long-term diabetes remission

Comparison with medical treatment

control (23% vs 5% HbA1c <6%, respectively), other cardiovascular risk fac-

ANTIDIABETIC MECHANISM OF ACTION

SLEEVE GASTRECTOMY AND TYPE 1 DIABETES

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