ONE YEAR RESULTS OF AN ENDOSCOPIC, DUODENAL-JEJUNAL EXCLUSION DEVICE FOR WEIGHT LOSS AND CONTROL OF TYPE
2 DIABETES

1Gastrointestinal Endoscopy Unit, Department of Gastroenterology, University of Sao Paulo Medical School,Sao Paulo, Brazil

2

Gastro Obeso Center, Sao Paulo, Brazil

3

Digestive Surgery, Department ofGastroenterology, University of Sao Paulo Medical School, Sao Paulo, Brazil 4Endocrinology and Metabolism
Department; University of Sao Paulo Medical School; Brazil
Eduardo G H de Moura1,Bruno C Martins1,Guilherme S Lopes1,Ivan R B Orso1,Suzana L Oliveira1,Manoel P
Galvao-Neto2,Marco

Aurelio

Santo3,Marcio

C

Mancini4,Paulo

Sakai1,AlminoC

Ramos2,Arthur

B

Garrido-Junior3,Alfredo Halpern4,Ivan Cecconello3

Background:

The duodenal-jejunal bypass liner (DJBL, GI Dynamics, Inc., Lexington, MA) is an endoscopic

implant that mimics the intestinal bypass component of the Roux-en-Y gastric bypass.

Previously reported

studies have shown promising improvements in type 2 diabetes (T2D) and weight loss for up to 6 months.
This report describes improvements in T2D and metabolic changes in subjects with T2D who were implantedwith the DJBL for one year. Methods:

This is a prospective, non-randomized, open label study with 22

patients enrolled. Inclusion criteria:

Age higher 18 years and less 65 years, BMI higher 35 kg/m; andtype 2 diabetes with or without other co-morbidities, unsuccessful history with nonsurgical weight
reduction methods, candidates to bariatric surgery.

There were 9 early endoscopic removals due to device

movement (3), nausea/vomiting (1), abdominal pain (1), GI hemorrhage (1), non-device related abdominal
neoplasm (1) and Principal Investigator request (2).Results:

At one year (n=13 patients), observed

absolute weight loss of 20.4 kg (p less 0.0001), excess weight percentage loss of 35.3% (p less 0.0001),
body mass index of 7.4 kg/m2 (p less 0.0001) and waist circumference of 10.1cm (p=0.0001) was observed.
Likewise, glucose levels decreased from 175.6 to 126.7 mg/dL (p less 0.0001) and glycosilated hemoglobinfrom 8.8 to 6.4% (p less 0.0001). The use of diabetic medications, except metformin was reduced and 19.2%of patients no longer required any anti-diabetic drugs.

Insulin (p=0.02) and C-peptide (p=0.015),

cholesterol (p=0.001), LDL (p=0.01), and triglycerides (p=006) levels were normalized at 1 year.
Conclusions: The endoscopic DJBL has a durable effect on glucose control, weight loss and metabolic
function for one year, suggesting this new device is a suitable option for the treatment of T2D and obesity.

Enteropeptidase: a gene associated to a starvation human phenotype as a novel target for the treatment
obesity and type II diabetes1ObeTherapy, Drug Discovery, Evry, FranceItzik Harosh1,Sandrine Braud1- Many obesity related genes have been proposed as targets for the treatment of obesity. However, theseobesity genes did not provide efficient drug therapy for obesity treatment. This is mainly due to theredundancy of the biochemical pathway involved in obesity and the lack of specificity of the gene targets.
It is therefore a challenge to identify crucial gene(s) targets involved in energy metabolism associatedwith lean or starvation phenotype. Congenital Enteropeptidase defficiency is an extremly rare pathology
which answer to all these criteria. Enteropeptidase catalyzes the conversion of inactive trypsinogen
into active trypsin via the cleavage of the acidic propeptide from trypsinogen We have generated knockout transgenic mice for enteropeptidase which shows the same phenotype like in human. These data andin vivo preclinical data using per os small molecule for long term treatment (9 weeks) will be presented.

Newly developed profiling of lipoproteins by PAGE to determine the heterogeneity of low-density
lipoproteins (LDLs)

1Department of Rehabilitation,Kamagarya General Hospital, Chiba, Japan 2Department of Diabetes andEndocrinology, Saitama Medical University, Saitama , Japan 3Department of Biochemistry, Saitama MedicalUniversity, Saitama , Japan 4ASKA Special Laboratory CO.,LTD., Kanagawa, Japan
Yuichi Shinoda1,Ikuo Inoue2,Takanari Nakano3,Makoto Seo3,Seiichiro Takahashi4,Takuya Awata2,Shigehiro
Katayama2

Aim: To explore the potential of newly developed polyacrylamide-gel disc electrophoresis (PAGE) for
lipoprotein profiling in clinical practice. Design and Methods: Blood samples were collected from 95
patients with metabolic syndrome. Lipid parameters were assayed by commercial (Lipophor) and newly
developed PAGE (Lipophor AS), including small, dense low-density lipoprotein (LDL) (n = 41), andtriglyceride-rich lipoprotein remnant cholesterol (n = 37). We also used a commercial kit to measuresmall, dense LDL (n = 41). Resutts: By PAGE, we obtained the percentage of the area under the curve (AUC %)of each peaks and calculated respective AUC% x total cholesterol (AUC%xTC) values. The calculated valuesof LDL-AUC%xTC, small LDL-AUC%xTC, and HDL-AUC%xTC values were correlated well with values fromhomogeneous assay for LDL-cholesterol, small, dense LDL-cholesterol, and HDL-cholesterol assays (r =0.94, 0.81, and 0.89, respectively). Lipophor AS is better corelation between TG and VLDL than Lipophor(r= 0.77, and 0.85, respectively). Conclusions: PAGE combined with measurement of total cholesterol andtriglycerides provides a rapid evaluation of anti- or pro-atherogenic lipoproteins and a simple profilingsystem for both the "quantity" and "quality" of lipoproteins, allowing a better assessment of the riskof coronary artery diseases.

leal interposition improves Glucose Tolerance and Insulin Resistance in Otsuka Long-Evans Tokushima Fattyrats.

1

Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Graduate Schoolof Medicine, Sendai,Japan 2Department of Surgery, Sendai City Medical Center
Fumie Ikezawa1,Chikashi Shibata1,Hirofumi Imoto1,Daisuke Kikuchi1,Takeshi Naitoh1,Takashi Tsuchiya2,Iwao
Sasaki1

Backgrounds:

Ileal interposition (IT) is an operative procedure in which the distal ileum istransposed isoperistaltically into the proximal jejunum and considered as a procedure for metabolic oranti-diabetic surgery.

Our aim was to study the effects of IT on glycemic control, fat metabolism, andhormonal changes in obese rats with spontaneous diabetes (OLETF rats).Methods:
into either an IT or a sham (SH) group.
and 8 weeks after the operation.

Animals were divided

They underwent oral glucose tolerance test (OGTT) before, 4,All animals were killed 10 weeks after operation for analyses of tissue

weight (liver, pancreas, epididymal fat, brown fat) and fasting plasma levels of glucose, insulin,
glucagon-like peptide (GLP)-1, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP),and leptin.

Results:

After operation, body weight increased in both groups compared to theirpreoperative weight, but it did not differ between IT and SH.

A 8 weeks postoperatively, integrated

blood glucose levels during the OGTT were decreased in IT compared to SH (p<0.05).

Ten weeks after

operation, fasting plasma levels of insulin, GLP-1, and GIP did not differ between the two groups, but
PYY levels were greater in the IT group (P<0.01).

Weight of epididymal and brown adipose tissues,

homeostasis model assessment insulin resistance, and fasting plasma leptin levels were decreased in theIT group (p<0.05).

Conclusions:

These results suggest that IT improves glucose and lipid metabolism

by decreasing blood glucose, insulin resistance, and epididymal fat, increases in plasma PYY might be
one of the mechanisms of these changes.

The effects of duodeno-jejunal bypass on glucose metabolism in obese type2 diabetic rat model.

1

Department of surgery, Division of biological-regulation and oncology, Tohoku university graduate schoolof medicine, Sendai, Japan
Hirofumi Imoto1,Shibata Chikasi1,Takeshi Naitoh1,Fumie Ikesawa1,Masayuki Kakyo1,Makoto Kinouchi1,NaokiTanaka1,Koh Miura1,Hitoshi Ogawa1,Iwao Sasaki1

BACKGROUNDS: Bariatric surgery, especially gastric bypass or duodenal switch, has been shown to improvetype 2 diabetes. However, its detail mechanisms are not well comprehended yet. There are two hypotheses
that are advocated to explain effects of bariatric surgery on glucose metabolism: the foregut hypothesis
and the hindgut hypothesis. The former theory is considered to depend on exclusion of duodenum and proximal
jejunum from the nutrients transit, possibly enhancing secretion of anti-incretin factors, while thelatter one is thought to be results from more rapid delivery of nutrients to the ileum, thereby enhancing
the release of hormones such as glucagon-like peptide-1 (GLP-1). Duodeno-jejunal bypass (DJB) might
include both theories, but it is still controversial which theory is dominant.METHODS: Male 20-week-old
OLETF rats were divided into 3 groups and they underwent sham operation or two types of DJB, which aredefined as DJB-J and DJB-I. These are differentiated by the length of alimentary limb (AL). In DJB-J,
the biliopancreatic limb (BPL) was anastomosed to the side of distal limb to make 2.5cm AL and it canbe considered as pure foregut model.

In DJB-I, the BPL was anastomosed to the distal limb 25cm proximal

to the ileum-end, and it can be thought as foregut plus hindgut model. All rats underwent OGTT at baseline,
4 and 8 weeks after surgery.RESULTS: There was some weight controlling effect in DJB-I group, but notin other groups. Regarding OGTT, DJB-I group demonstrated lower plasma glucose curve at 4 and 8weeks
after surgery comparing to other groups, but there were no significant difference between DJB-J and shamgroup. CONCLUSION: The improvement of glucose metabolism in DJB mainly depends on an inflow of bile andpancreatic juice to the ileum, and the exclusion of the duodenum may not contribute to the anti-diabeticeffect.

Differential increase in HDL-c post bariatric surgery for Singaporean Patients according to GlucoseStatus.

1

Department of Endocrinology, Singapore General Hospital, Singapore 2Department of Surgery, Singapore

General Hospital
Daniel C. Wai1,Shanker Pasupathy2,Sonali Ganguly1,Kwang W. Tham1

Background: HDL-c is negatively correlated with cardiovascular risk. Patients with diabetes andpre-diabetes or abnormal glucose tolerance (AGT) have low HDL-c. Few studies have compared the changeof HDL-c post bariatric surgery between patients with normal glucose tolerance (NGT) and AGT.Aims ofStudy: To compare the change of HDL-c post bariatric surgery between patients with NGT and AGT.

Methods:HDL-c levels at 0, 3 and 6 months were transformed using the multivariate repeated measures model, withglucose tolerance being the between-subject factor.Results: 46 patients (61% females) underwent
laparoscopic bariatric surgery from September 2008 to November 2010. 78% had sleeve gastrectomy, 20%
gastric bypass, and 2% bilio-pancreatic diversion. The mean age was 39 years (+/-10.6) with a mean BMIof 43.6kg/m2 (+/-9.8). 54% had NGT versus 46% with AGT. Only 1 patient (4%) in the NGT group was on afibrate pre-op but none in the AGT group. Average weight loss at 6 months was 25.5kg and 22.2kg for NGTand AGT respectively. HDL-c rose significantly in both groups (mean HDL-c for NGT were 1.06, 1.49 and1.68 mmol/L at 0, 3 and 6 months; mean HDL-c for AGT were 0.89, 0.92 and 1.08 mmol/L; within-subjectp=0.006). Thus HDL-c increased 58% in the NGT but only 21% in the AGT. HDL-c in the NGT was significantly
higher than in the AGT group throughout the 6 months (between-subject p=0.009).