OBES SURG (2009) 19:307–312DOI 10.1007/s11695-008-9759-5
Jejunal Exclusionin the Treatment of Type 2 Diabetes Mellitusin Patients with BMI < 30 kg/m2 (LBMI)
Almino C. Ramos & Manoel P. Galvão Neto &Yglésio Moyses de Souza & Manoela Galvão &Abel H. Murakami & Andrey C. Silva &Edwin G. Canseco & Raúl Santamaría &Trino A. Zambrano
Received: 30 May 2008 / Accepted: 15 October 2008 / Published online: 6 November 2008
Springer Science + Business Media, LLC 2008
Results There was a BMI decrease up to the third month
Background The association between medical and dietetic–
and a weight stabilization between the third and sixth
behavioral treatments of type 2 diabetes mellitus (T2DM)
months. There was a significant reduction in fasting
has demonstrated to have variable results. The surgical
glycemia (43.8%) and HbA1c (22.8%) up to the sixth
treatment of T2DM is justifiable after the observation of a
month (p<0.001). C-peptide did not show any significant
successful glycemic control in patients submitted to Roux-
alteration until the third month, although there was a
en-Y gastric bypass and biliopancreatic diversion. Experi-
considerable increase (25%) between the third and the sixth
ments have shown an important role of the proximal
months (p < 0.001). Only two patients were on oral
intestine in glycemia decrease and diabetes control.
Methods Twenty diabetic patients underwent laparoscopic
Conclusions Preliminary results have shown an important
duodenal–jejunal exclusion. The variables studied were
effect of the laparoscopic duodenal–jejunal exclusion in the
body mass index (BMI), fasting glycemia, glycosylated
treatment of T2DM. Studies with longer follow-up and a
hemoglobin (HbA1c), and C-peptide, in the preoperative
larger number of patients are necessary to better define the
role of this new and promising procedure.
Dr. Almino Ramos and Dr. Manoel P. Galvão Neto are international
Keywords Diabetes mellitus . Duodenal–jejunal exclusion .
consultants for Ethicon Endo-Surgery® and GI Dynamics®.
A. C. Ramos Y. M. de Souza M. Galvão A. H. Murakami
A. C. Silva E. G. CansecoGastrointestinal, Bariatric and Metabolic Surgery,Gastro Obeso Center,
Diabetes mellitus affects nearly 150 million people all over
the world. This number may double by 2025 . In the
Gastrointestinal, Bariatric and Metabolic Endoscopy,Gastro Obeso Center,
USA, it is the leading cause of blindness, chronic renal
insufficiency, and amputations, multiplying by three therisks of heart diseases and by two the risks of a stroke. The
annual health system expenditures amount to 100 billion
Division of Bariatric and Metabolic Surgery, San Obeso Center,Guayaquil, GU, Ecuador
American dollars It is type 2 diabetes mellitus (T2DM)that predominates in about 90% of patients, usually
associated with intolerance to glucose and overweight.
Rua Barata Ribeiro, 237-cj. 83/84, Cerqueira Cesar,
The treatment of T2DM in the past few years has been
São Paulo, SP CEP: 01308-000, Brazile-mail: firstname.lastname@example.org
based upon a combination of dietetic–behavioral proce-
dures and medical therapy with oral hypoglycemiants and,
shears, Ethicon Endo-Surgery, Cincinnati, OH, USA),
in more severe cases, insulinotherapy with variable success
preserving the gastroepiploic vessels until the head of the
rates . The large variability in clinical treatment results
pancreas is reached. Once in the retrocavity, the dissection
and the growing economic impact of the DM treatment and
is extended to the lesser curvature for freeing the first
its complications worldwide justify the search for new and
duodenal portion (about 2 cm distal to the pylorus), where a
efficient treatment methods, whether clinical or surgical. In
45-mm linear stapler (ETS-Flex Endoscopic Articulating
the past two decades, with the advancement of bariatric
Linear Cutter, Ethicon Endo-Surgery) with a vascular white
surgery and the observation of a successful glycemia
load is fired (Fig. ). Pyloric artery ligation is always
control in patients who underwent Roux-en-Y gastric
performed to achieve a tension-free duodenojejunostomy.
bypass and biliopancreatic diversion (Scopinaro & Duode-
A jejunal omega isoperistaltic loop 200 cm from the
nal Switch), many groups have been trying to elucidate the
Treitz ligament is shown in an antecolic isoperistaltic
mechanisms associated with glycemia control [–]. At
fashion. A 45-mm linear stapler (vascular) performs the
first, it was thought that glycemia stabilization would be a
terminolateral duodenojejunostomy. The stapled hole is
direct consequence of weight loss induced by surgery.
closed by a layer of continuous suture with PDS 3.0®
Rubino et al. carried out a study with non-obese diabetic
rats which underwent duodenal–jejunal exclusion, having
By mobilizing the alimentary limb on the surgeon’s left
found a significant glycemia decrease in about 40% of them
side, a side-to-side enteroenterostomy is performed with a
and an improvement in tests of glucose oral tolerance
45-mm vascular stapler 100 cm distal from the duodeno-
(better result than clinical treatment with rosiglitazone).
jejunostomy. Roux-en-Y reconstruction is completed
Independent from any ponderable weight loss, this effect
through stapling between the duodenojejunostomy and the
was confirmed within a 3-week postoperative observation
enteroenterostomy with a 45-mm vascular stapler (Fig.
]. In this setting, a study protocol of 20 patients with
Mesenteric defects are closed with an Ethibond® 3.0
low body mass index (LBMI) was designed in which they
running suture. A tubolaminar drain is left next to the
underwent laparoscopic duodenal–jejunal exclusion, under
duodenojejunostomy until the seventh postoperative day.
informed consent, aiming to control glycemia and to
A hypoglycemic/hypolipidemic diet is started on the first
improve the conditions associated with T2DM.
postoperative day. Patients are stimulated to walk, beingdismissed from the hospital on the second postoperativeday. Dosages of fasting glycemia, HbA1c, C-peptide, and
BMI calculation are taken at postoperative days 30, 90, and180. Glycemic control at home is maintained as in the
From August 2006 to October 2007, we started aprospective study in patients with BMI between 20 and30 kg/m2, aged between 18 and 60 years old, with diabetesbeing diagnosed later than two and earlier than 8 years,without a history of insulinotherapy and with C-peptidelevels >1.0 ng/ml. All patients were explained the risks andbenefits of this new technique and have provided informedconsent term approved by the local Institutional ReviewBoard.
Patients taking hypoglycemiants different from metfor-
min, glimepiride, and glitazones, with a previous history ofdifficult glycemic control or ketoneacidosis, with a weightloss of more than 5 kg in the last 3 months or with HbA1c>11% were excluded from this protocol.
Positioning of patient, surgical team, and punctures aresimilar to that in a five-trocar antireflux procedure. Thegreater omentum is divided at the greater gastric curvaturewith the use of a harmonic scalpel (Harmonic ACE 5 mm
Fig. 1 Transection of the first duodenal portion
sary. It was necessary to use the logarithmic transformationin the variable fasting glycemia. Values of p<0.05 wereconsidered significant . The statistical analysis weremade by the software “Statistical Package for SocialSciences” version 11.0 for Windows.
Twenty patients were included in the study (11 men and ninewomen). Mean age was 43 (29–60) years old. The meanT2DM diagnosis time was 5.3 (2–8) years. Mean preoperativeBMI was 27.1 (25–30). Mean BMI in the third and sixthpostoperative months were respectively 25 (22–29) and 24.4(20.2–28.3). A statistically significant difference was ob-served between BMI in the preoperative period and in thethird month (p<0.001). However, there was no differencebetween the third and the sixth months (p=0.732), showing aweight loss stabilization, around 7.8% below the initialweight (Fig.
Preoperative fasting glycemia level was 171.3 (127–242).
After the third and the sixth postoperative months, there was a
Fig. 2 Creation of the duodenoenterostomy 200 cm from the Treitz
reduction of 37.5% and 43.8% (p<0.001), respectively.
Comparing the third and the sixth postoperative months,there was a significant difference (p=0.047; Fig. ).
Concerning HbA1c, the mean value in the preoperative
1c, fasting glycemia, and C-peptide data were
checked using analysis of variance, together with multiple
period was 8.8% (7.5–10.2). There was a decrease to 7.8
comparisons through the Bonferroni method when neces-
Fig. 3 Formation of the enteroenterostomy, 100 cm from the previous
Fig. 4 BMI evolution up to the sixth postoperative month. PRE
anastomosis and the jejunal section for the final bypass positioning
preoperative data, 3M 3 months, 6M 6 months
Fig. 7 C-peptide up to the sixth postoperative month. C PEP C-
Fig. 5 Fasting glycemia up to the sixth postoperative month. PRE
peptide, PRE preoperative data, 3M 3 months, 6M 6 months
preoperative data, 3M 3 months, 6M 6 months
(6.7–9.6) and 6.8 (5.8–7.9) in the third and sixth postop-
and 2.5 (1.7–3.2). However, there was no statistical
erative months, respectively (p<0.00l; Fig.
significance up to the third month (p=0.247). In the sixth
The mean value of C-peptide levels in the preoperative
month, there was an increase of 25% in the C-peptide levels
period was 2.0 ng/ml (1.2–3.4). In the third and sixth
(p<0.001; Fig. ). Results are summarized in Table .
postoperative months, there was an increase to 2.1 (1.5–2.9)
Only two patients (10%) included in this study were kept
on oral medication (metformin) after the sixth postoperativemonth. Patients are still on clinical follow-up aiming along-term analysis. There have been no postoperativecomplications, such as fistulae or abscesses in this groupof patients. No mortality was observed.
Table 1 Comparative results between BMI, HbA1c, glycemia, and C-peptide in different collection moments
PRE > 3M (p<0.001a)PRE > 6M (p<0.001a)3M = 6M (p=0.732a)
PRE > 3M (p<0.001a)PRE > 6M (p<0.001a)3M > 6M (p<0.001a)
PRE > 3M (p<0.001a)PRE > 6M (p<0.001a)3M > 6M (p=0.047a)
PRE = 3M (p=0.848a)PRE < 6M (p<0.001a)3M < 6M (p<0.001a)
Fig. 6 HbA1c up to the sixth postoperative month. PRE preoperative
PRE preoperative data, 3M 3 months, 6M 6 months
in the regulation of glucose metabolism , TheHbA1c reduction was the result of a better glycemic control
In recent years, some procedures have been proposed in the
and the C-peptide increase was the result of improvement
literature for the treatment of T2DM in non-obese and
of the pancreatic function, probably as a consequence of
obese patients, as the duodenal–jejunal exclusion and
the ileal interposition ]. We have chosen the duodenal–
The idea of bypassing the duodenum and proximal
jejunal exclusion based on the consistent results on
jejunum as a means of achieving glycemic control was first
glycemia control reported by Rubino et al. in an experi-
developed in animal models [, ]. This concept has
mental protocol in Goto–Kakizaki non-obese diabetic rats
evolved leading to the pioneers well-succeeded attempts of
The option for creating a biliopancreatic limb ranging
surgical ] and endoscopic ] duodenal–jejunal exclu-
200 cm from Treitz and an alimentary limb of 100 cm was
sions. In the former study , which included two
based in the literature data [and our group’s experience
patients, by the fifth week after surgery, both were
in bariatric surgery with the Roux-en-Y gastric bypass in
euglycemic and free of all antidiabetic medications. The
morbidly obese patients who also had hyperlipidemia and
HbA1c levels were <6% at the last follow-up visit, 9 months
T2DM or glucose intolerance. We have observed a
postoperatively. In the latter trial [glycemia control
reduction in blood levels of glucose and cholesterol and
occurred already 24 h after the initial procedure. De Paula et
the resolution of T2DM in most of our cases (unpublished
al. proposed a procedure combining an ileal interposition
data). The choice for the laparoscopic method was due to its
with sleeve gastrectomy in the treatment of T2DM. An
benefits in terms of postoperative recovery, surgical
important reduction in antidiabetic medications was ob-
served. Nearly 87% of the patients permanently discontinued
The inferential results showed that the BMI behavior
preoperative oral hypoglycemic agents, insulin, or both. A
(p<0.001), HbA1c (p<0.001), fasting glycemia (p<0.001),
rapid normalization of fasting plasma glucose was achieved
and C-peptide (p<0.001) are not statistically the same in
by 29% of the patients on the first 2 weeks. However, it is a
the different moments of postoperative follow-up. We
technically challenging procedure, with major morbidity and
verified a weight loss of approximately 7.8% of the total
mortality rates of 10.3% and 2.6%, respectively .
body weight up to the third month and stabilization from
Generally, the goals to be reached in the clinical
the third to the sixth months. There was an important
treatment of T2DM are a fasting glycemia around 100–
decrease in fasting glycemia up to the third month,
110 mg/dl and HbA1c at the most 1% above the upper limit
followed by a lower reduction after the sixth month. The
of the reference value ]. In the present study, the
reduction of HbA1c levels was more stable, 11.4% and
duodenal–jejunal exclusion was efficient by achieving these
22.8% in the third and the sixth postoperative months,
goals. Despite having no clinical randomization or sample
respectively. C-peptide levels increased in the sixth month
pairing for comparison with a group of patients submitted
dosage, probably reflecting a slower recovery of the
to clinical treatment in the same institution, the present
pancreatic function and insulinic activity in the postopera-
study showed a remarkable hypoglycemiant effect of
laparoscopic duodenal–jejunal exclusion in the treatment
Six months after the duodenal–jejunal exclusion, only
10% of the patients were still taking oral hypoglycemiants.
One of those has had the diagnosis of T2DM for 8 years,the longest in our series. The other patient, although after
only 4 years of his T2DM diagnosis, showed no improve-ment in the C-peptide levels, demonstrating a lack of
The laparoscopic duodenal–jejunal exclusion is a safe
improvement in insulinic secretion. Cohen et al. pointed
procedure with low postoperative complication rates and
the better response to surgery in a subset of patients
an incretinic effect, shown through the reduction of
with shorter disease time and higher pre-operative levels of
glycemia and HbA1c and the increase of C-peptide
secretion in a subset of patients. Further studies with larger
Concerning the association between weight loss and
samples, randomization, and longer follow-up are necessary
glycemic reduction and the improvement in the levels of
to clarify its role in the treatment of T2DM.
HbA1c and C-peptide, it can be said that weight loss andglycemic reduction were combined events up to the thirdmonth. However, there was no combination up to the sixth
month, showing a possible hypoglycemiant effect throughthe increase of incretins. Many publications have pointed
1. Zimmet P, Alberti K, Shaw J. Global and societal implications of
the importance of these gut hormones (GLP-1, PYY, GIP)
the diabetes epidemic. Nature 2001;414:782–7.
2. Greenway SE, Greenway FL, Klein S. Effects of obesity surgery
of the proximal small intestine in the pathophysiology of type 2
on non-insulin-dependent diabetes mellitus. Arch Surg
diabetes. Ann Surg 2006;244:741–9.
11. Neter J, Kutner MH, Nachtsheim CJ, et al. Applied linear
3. Eliasson B, Eeg-Olofsson K, Cederholm J, et al. Antihypergly-
statistical models. 4th ed. Chicago: Irwin; 1996.
caemic treatment of type 2 diabetes: results from a national
12. Cohen R, Schiavon C, Pinheiro J, et al. Duodenal–jejunal bypass
diabetes register. Diabetes Metab. 2007;33:269–276.
for the treatment of type 2 diabetes in patients with body mass
4. Pories WJ, Macdonald KG, Flickinger EG, et al. Is type II
index of 22–34 kg/m2: a report of 2 cases. Surg Obes Relat Dis
diabetes mellitus (NIDDM) a surgical disease? Ann Surg 1992;
13. de Paula AL, Macedo A, Prudente L, et al. Laparoscopic sleeve
5. Pories WJ, Macdonald KG, Long SB, et al. Who would have
gastrectomy with ileal interposition (“neuroendocrine brake”)—
thought it? An operation proves to be the most effective therapy
pilot study of a new operation. Surg Obes Relat Dis 2006;2:464–7.
for adult-onset diabetes mellitus. Ann Surg 1995;222(3):339–52.
14. Leifsson BG, Gislason HG. Laparoscopic Roux-en-Y gastric
6. Lee WJ, Huang MT, Wang W, et al. Effects of obesity surgery on
bypass with 2-metre long biliopancreatic limb for morbid obesity:
the metabolic syndrome. Arch Surg 2004;139:1088–92.
technique and experience with the first 150 patients. Obes Surg
7. Madan AK, Orth W, Ternovits CA, et al. Metabolic syndrome: yet
another comorbidity gastric bypass helps cure. Surg Obes Relat
15. Näslund E, Backman L, Holst JJ, et al. Importance of small bowel
peptides for the improved glucose metabolism 20 years after
8. Mottin C, Padoin AV, Schroer C, et al. Behavior of type 2 diabetes
jejunoileal bypass for obesity. Obes Surg 1998;8(3):253–60.
mellitus in morbid obese patients submitted to gastric bypass.
16. Rodriguez-Grunert L, Galvão-Neto MP, Alamo M, et al. First
human experience with endoscopically delivered and retrieved
9. Rubino F, Marescaux J. Effect of duodenal–jejunal exclusion in
duodenal–jejunal bypass sleeve. Surg Obes Relat Dis 2008;4
non-obese animal model of type 2 diabetes: a new perspective for
an old disease. Ann Surg 2004;239:1–11.
17. Chobanian AV, Bakris GL, Black HR. The seventh report of the joint
10. Rubino F, Forgione A, Cummings DE, et al. The mechanism of
national committee on prevention, detection, evaluation and treat-
diabetes control after gastrointestinal bypass surgery reveals a role
ment of high blood pressure (JNC 7). JAMA 2003;289:2560–71.
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