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Oral Presentations

WCIDT-0134
Clinical Outcomes of Metabolic/Diabetes Surgery

FIVE-YEAR OUTCOMES AFTER SURGERY AND MEDICAL THERAPY FOR TYPE


2 DIABETES: A RANDOMIZED CLINICAL TRIAL
S. Panunzi1, G. Mingrone2,3, A. De Gaetano1, C. Guidone2, A. Iaconelli2, G. Nanni4,
M. Castagneto4, S. Bornstein3,5, F. Rubino6
1
BioMatLab, CNR-Institute of Systems Analysis and Computer Science IASI, Rome,
Italy
2
Università Cattolica S. Cuore, Department of Internal Medicine, Rome, Italy
3
King’s College London, Diabetes and Nutritional Sciences- Hodgkin Building-
Guy’s Campus, London, United Kingdom
4
Università Cattolica S- Cuore, Department of Surgery, Rome, Italy
5
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden,
Department of Medicine III, Dresden, Germany
6
King’s College London and King’s College Health Partners,
Chair of Metabolic and Bariatric Surgery, London, United Kingdom

Background: Randomized-clinical trials (RCT) have shown that bariatric surgery is


more effective than conventional treatments in the short-term control of type-2
diabetes-mellitus (T2DM).

Methods: Sixty T2DM subjects (BMI>35kg/m2, diabetes history>5 years) were


randomized to either medical therapy (MT) or surgery (Roux-en-Y Gastric-Bypass –
RYGB- or Biliopancreatic Diversion -BPD). The primary endpoint (2-year remission of
hyperglycemia defined as HbA1c≤6.5%+fasting glycemia≤ 5.6mmol/l without ongoing
pharmacologic treatment for one year) was achieved by 95%, 75% and 0% of
subjects in the BPD, RYGB and MT groups, respectively. We analyze here glycemic
and metabolic control, cardiovascular risk, medication usage, quality of life (QoL) and
long-term complications at 5 years after randomization.

Findings: Overall, 50% of surgical patients (63% BPD and 37% RYGB) and 0% of
subjects undergoing MT maintained remission at 5-year (P<0.001). Diabetes relapse
was 37% for BPD and 53% for RYGB. Fifty-four percent of surgical patients had
HbA1c≤6.5% with or without medications compared with 27% of MT subjects
(P<0.05). Surgical patients lost more weight but weight changes did not predict
diabetes remission or relapse after surgery. Both surgical procedures were
associated with significantly lower plasma lipids, cardiovascular risk and medication
usage. QoL was better in surgical patients and best in RYGB subjects (p<0.01).
Medically-treated patients had more diabetes-related complications, including one
fatal myocardial infarction. No late surgical complications or mortality were observed.
Nutritional side effects were noted mainly after BPD.

Interpretation: Surgery is more effective than medical treatment in the long-term


control of obese T2DM and should be considered in the treatment algorithm of this
disease. Continued monitoring of glycemic control, however, is warranted due to
potential relapse of hyperglycemia. ClinicalTrials.gov number, NCT00888836
WCIDT-0149
Clinical Outcomes of Metabolic/Diabetes Surgery

SAFETY PROFILE AND HEALTHCARE USAGE OF BARIATRIC-METABOLIC


SURGERY COMPARED TO COMMONLY PERFORMED ELECTIVE
PROCEDURES
D. Tassinari1, S. Panagiotopoulos1, E. Giorgakis1, L. Castagneto-Gissey1,
J. Casella Mariolo1, A. Salerno1, A. Chang1, A. Patel1, A. Haq2, S. Ramar1,
G. Galata2, K.M. Schulte2, F. Rubino1
1
Metabolic and Bariatric Surgery, Division of Diabetes and Nutritional Sciences,
James Black Centre, King's College London, Denmark Hill Campus, London, UK
2
Department of Surgery, King's College Hospital, Denmark Hill, London

Introduction: Bariatric/metabolic surgery is widely perceived as an effective but high-


risk and costly intervention. We compared peri-operative safety and healthcare usage
after bariatric surgery and other commonly performed elective procedures.

Methods: Data were obtained from a prospective database of a newly established


metabolic surgery program and retrospective electronic chart review of elective
procedures at the same hospital. Bariatric/metabolic surgery was compared to hernia,
gallbladder, neck, adrenal, gastro-esophageal (GE) and colorectal surgery. One
hundred consecutive cases for each surgery were analysed. Emergency, acute
illnesses, day-surgery and cancer cases were excluded. Outcome measures included
demographics, baseline surgical risk (assessed by ASA and CCI score), hospital stay
(LoS), 30-day major complications, reoperations and readmissions.

Results: The study included 700 patients. Bariatric/metabolic surgery patients were
younger (mean age 46.5yo) but had the highest baseline surgical risk. Mean LoS for
metabolic/bariatric surgery was 2.3+1.2 days (range 1-8), similar to gallbladder
(2.3+3.3 days; range 1-30) and hernia (2.2+2.2 days; range 2-18) but significantly
lower than colorectal surgery (10.9+7.8 days). Major 30-day complication rate was
16, 8, 2% for colorectal, GE and gallbladder surgery respectively, 1% for neck and
adrenal surgery and 0% for hernia and metabolic/bariatric surgery (ANOVA p<0.01).
There were no 30-day readmissions for bariatric/metabolic surgery. Reoperations rate
was 10, 3, and 1% for colorectal, GE, gallbladder, neck and hernia surgery
respectively and 0% for both adrenalectomy and bariatric/metabolic surgery. There
was no mortality in any group.

Conclusion: Contrary to widespread perceptions, bariatric/metabolic surgery is


associated with high safety profile and low healthcare usage.
WCIDT-0032
Clinical Outcomes of Metabolic/Diabetes Surgery

VASOPROTECTIVE PROPERTIES OF HDL IMPROVE EARLY AFTER ROUX-EN-


Y GASTRIC BYPASS BUT NOT AFTER DIET TREATMENT: THE SUPERIOR
CARDIOMETABOLIC BENEFITS OF RYGB
E. Osto1, E. McLoughlin2, P. Doytcheva3, J. Manz3, M. Charakida2, N. Finer4,
L. Van Gaal5, J. Deanfield2, T. Lüscher3
1
Center for molecular cardiology,
Center for molecular cardiology and cardiology department- university of zurich,
Schlieren-Zurich, Switzerland
2
Institute of Cardiovascular Science- University College London,
Institute of Cardiovascular Science- University College London, London,
United Kingdom
3
Center for molecular cardiology,
Center for molecular cardiology and cardiology department- university of zurich,
Zurich, Switzerland
4
National Centre for Cardiovascular Prevention and Outcomes-
UCL Institute of Cardiovascular Science,
National Centre for Cardiovascular Prevention and Outcomes-
UCL Institute of Cardiovascular Science, London, United Kingdom
5
Department of Endocrinology- Diabetology and Metabolism-
Antwerp University Hospital, Department of Endocrinology-
Diabetology and Metabolism- Antwerp University Hospital, Antwerp, Belgium

Roux-en-Y gastric bypass (RYGB) reduces cardiometabolic risk through different


potential mechanisms. High density lipoprotein cholesterol (HDL) changes might
explain part of this benefit. We assessed the effect of RYGB on HDL vasoprotective
properties in comparison with a hypocaloric diet. HDL was isolated from serum of
obese patients (BMI > 35 kg/m2) before and 6 months after RYGB (n=32) or diet
(n=32). In endothelial cells stimulated with HDL, we quantified nitric oxide (NO)
production by DAF-2 fluorescence and paraoxonase-1 antioxidant activity (PON-1).
Total cholesterol, low density lipoprotein (LDL-C), HDL-C, and triglycerides (TG) were
also measured. At baseline there was no significant difference in mean body weight
(BW) and BMI between RYGB and diet patients (119.9 Kg; 42kg/m2 vs. 110.9 kg;
37.4 kg/m2, respectively, p=0.06). At 6 months, BW and BMI were not different
(RYGB: 94kg; 33 kg/m2; diet: 99kg; 33.4 kg/m2, p=ns). In both groups, mean total
cholesterol and TG were reduced; LDL-C decreased only after RYGB. Although total
HDL-C increased 6 months after both interventions, only RYGB improved the
vasoprotective HDL-stimulated NO production (RYGB: 234.2±178.0 vs diet 98.8±76.4
arbitrary units, p<0.0001) and HDL-associated PON-1 activity (RYGB: 40% vs diet:
9% increase compared to baseline; p<0.0001). Our study shows that although HDL
concentration increased after RYGB or diet-induced BW loss, endothelial protective
HDL properties were restored only after RYGB even though patients were still obese.
This suggests that BW loss is not sufficient or critical to improve the protective
properties of HDL, unless accompanied by yet unknown surgery-specific effects.
WCIDT-0013
The Science Behind Metabolic Surgery - The Mechanisms of Action of
Metabolic Surgery

ATTENUATION OF DIABETIC KIDNEY DISEASE IN THE ZUCKER DIABETIC


FATTY RAT FOLLOWING ROUX EN Y GASTRIC BYPASS
N. Docherty1, K. Neff1, J. Elliott1, S. Jackson1, D. Higgins1, C. Corteville2, T. Lutz2,
M. Bueter2, C. Godson1, C. le Roux1,3,4
1
University College Dublin, Diabetes Complications Research Centre-
School of Medicine, Dublin, Ireland
2
University of Zurich, Institute of Veterinary Physiology- Vetsuisse Faculty-, Zurich,
Switzerland
3
Imperial College London, Investigative Science, London, United Kingdom
4
University of Gothenburg, Gastrosurgical laboratory- University of Gothenburg,
Gothenburg, Sweden

Background- In patients with baseline proteinuria, Roux-en-Y Gastric Bypass


(RYGB) leads to early and sustained reductions in both urinary albumin and pro-
inflammatory chemokine excretion.

Aim-To interrogate in the Zucker Diabetic Fatty rat (ZDF) model of Diabetic Kidney
Disease (DKD), the correlates of the anti-proteinuric effects of RYGB and their
dependence on weight loss.

Methods-Eighteen week old ZDF fa/fa rats underwent RYGB (n = 7) sham surgery
(SS) alone (n = 6) or SS with body weight matching to the RYGB group (BWM n=8).
Zucker fa/+ rats (n = 5) acted as healthy controls. Urinary protein-creatinine ratios,
focal segmental glomerulosclerosis (FSGS), macrophage infiltration, renal MCP-1
expression and urinary MCP-1 excretion levels were assessed at follow up.

Results- RYGB reduced proteinuria, renal MCP-1 expression and urinary MCP-1
excretion in fa/fa rats. The percentage of glomeruli showing signs of FSGS was also
significantly reduced in RYGB fa/fa rats relative to SS fa/fa rats as was glomerular
hypertrophy and renal macrophage infiltration. BWM attenuated proteinuria to a
similar extent to RYGB early (4 weeks) but not at study end. BWM and RYGB were
equally effective at reducing renal inflammation.

Conclusions- RYGB induced remission of proteinuria is paralleled by structural


improvements in the kidney. BWM effectively decreases renal inflammation but does
not sustainably improve glycaemic control or proteinuria. Improvements in factors in
the metabolic milieu or renal insulin sensitivity by RYGB may dynamically influence
urinary protein excretion. These data support further evaluation of a role for RYGB as
a treatment modality for patients with DKD.
WCIDT-0067
The Science Behind Metabolic Surgery - The Mechanisms of Action of
Metabolic Surgery

PET-CT SCANNING REVEALS INCREASED INTESTINAL GLUCOSE UPTAKE IN


PATIENTS WITH PRIOR GASTRIC SURGERY
E. Franquet1, G.M. Kolodny1, A. Goldfine2, M.E. Patti2
1
Beth Israel Deaconess Medical Center, Department of Nuclear Medicine, Boston,
USA
2
Joslin Diabetes Center, Research Division, Boston, USA

Intestinal glucose uptake is increased after gastric bypass in rodents, potentially


contributing to reduced blood glucose and type 2 diabetes remission. To determine
whether intestinal glucose uptake is also increased in humans, we performed a
retrospective analysis of PET-CT performed clinically. We identified 19 patients over
age 18 with prior gastric surgery (roux-en-Y gastric bypass (n=10), sleeve
gastrectomy (n=1), or Billroth I (n=2) and II gastrectomy (n=6)). We identified 43
controls without gastric surgery, matched for age, gender, and indication for PET-CT.
Patients with gastrointestinal malignancy or metformin treatment were excluded.

Patients were instructed to fast for 3-5 hours prior to 18F-fluorodeoxyglucose injection
(4.2 MBq/Kg). Images were obtained 60 minutes later, and corrected by attenuation;
noncontrast low-dose CT was obtained. Fused and non-fused images were analyzed
blindly; standardized uptake values (SUV) were calculated for each region by
volumes of interest (VOI) at the region of highest activity. Both SUVmax (Table,
mean+SD) and SUVmean were significantly increased in jejunum, ascending, and
transverse colon by 41-98% in patients with prior gastric surgery. *p<0.05 vs.
controls.

We conclude that intestinal glucose uptake is increased in patients with prior gastric
surgery, potentially contributing to insulin-independent glucose uptake and reduced
glycemia. Prospective studies will be important to dissect the contributions of weight
loss, dietary factors, and systemic metabolism.
WCIDT-0106
The Science Behind Metabolic Surgery - The Mechanisms of Action of
Metabolic Surgery

DIFFERENCES IN REGIONAL BRAIN RESPONSES TO FOOD INGESTION


AFTER ROUX-EN-Y GASTRIC BYPASS (RYGB) AND THE ROLE OF GUT-
PEPTIDES: A NEUROIMAGING STUDY
K. Hunt1, J. Dunn2, P. Marsden2, C. le Roux3, A. Patel4, A. Pernet1, B. Wilson1,
S. Amiel1
1
King's College London, Diabetes Research Group, London, United Kingdom
2
King's College London, Division of Imaging Sciences & Biomedical Engineering,
London, United Kingdom
3
University College Dublin, Department of Pathology, Dublin, Ireland
4
King's College Hospital NHS Foundation Trust,
Department of Bariatric and Metabolic Surgery, London, United Kingdom

Improved appetite control, perhaps via exaggerated gut-peptide responses to eating,


may contribute to weight loss post-RYGB.

Aim: To compare brain responses to eating between post-RYGB, normal-weight


(NW) and obese non-operated (Ob) subjects and investigate effects of inhibiting gut-
peptide responses (using somatostatin) post-RYGB.

Methods: Twelve NW (BMI22.3±1.4kg/m2), 21 Ob (BMI34.1±2.6kg/m2) and 9 post-


RYGB (18±12months post-surgery, BMI34.0±3.3kg/m2) subjects underwent [18F]-
fluorodeoxyglucose positron emission tomography (FDG-PET) neuroimaging: once
FED, once FASTED. Post-RYGB were restudied with somatostatin. Regional brain
FDG uptake, a neuronal activation marker, was compared using Statistical
Parametric Mapping. Satiety was assessed using analogue scales and post-scan ad-
libitum meal.

Results: Fullness scores were higher post-RYGB vs NW or Ob (p=0.003, p=0.015)


and ad-libitum consumption lower (p=0.004, p=0.005). Brain responses to eating
were different (voxel-wise p<0.01, cluster-size threshold 100 voxels) in:
hypothalamus and pituitary (energy balance: similar activation in NW and Ob, greater
post-RYGB, p<0.001); right dorsolateral frontal cortex (inhibitory-control: deactivation
in NW and RYGB, absent in Ob, p<0.001); posterior cingulate, precuneus, angular
gyrus (default mode network: exaggerated deactivation post-RYGB versus NW and
Ob, p<0.001); and left medial orbital cortex (MOC) (reward salience: NW
deactivation, Ob no response, post-RYGB activation). Somatostatin in post-RYGB
inhibited gut-peptide responses and abolished MOC activation with no impact on
other responses.

Conclusions: In relation to eating, RYGB augments normal brain responses of


energy balance regions; restores lost inhibitory responses; and turns NW hedonic
responses, absent in obesity, to aversion. These altered responses may contribute to
weight loss. Gut-peptides may mediate the aversive response post-RYGB, but not
other differences in brain responses.
E-Poster Oral Presentations

WCIDT-0028
E-Poster Session

ACCELERATED PROTEIN DIGESTION AND AMINO ACID ABSORPTION AFTER


ROUX-EN-Y GASTRIC BYPASS
K. Bojsen-Moller1, S. Jacobsen2, C. Dirksen2, N. Jorgensen2, S. Reitelseder3,
J.E. Jensen2, V. Kristiansen4, J. Holst5, G. van Hall6, S. Madsbad2
1
Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
2
Copenhagen University Hospital Hvidovre, Dept. of Endocrinology, Hvidovre,
Denmark
3
Copenhagen University Hospital Bispebjerg,
Institute of Sports Medicine Copenhagen, Copenhagen, Denmark
4
Copenhagen University Hospital Hvidovre, Dept of Surgical Gastroenterology,
Hvidovre, Denmark
5
University of Copenhagen, Dept of Biomedical Sciences, Copenhagen, Denmark
6
Copenhagen University Hospital Rigshospitalet, Dept of Clinical Metabolomics,
Copenhagen, Denmark

Background: Roux-en-Y gastric bypass (RYGB) excludes the stomach from nutrient
passage and changes the admixture of gastro-pancreatic enzymes, which could
impair protein digestion.

Methods: Nine obese glucose tolerant subjects (BMI 39.2 [35.2, 43.3] kg/m2 (mean
[95%CI]), HbA1c 5.3 [4.9, 5.6] %) were studied before and 3 months after RYGB.
Leucine kinetics were determined under basal conditions and 4 hours postprandially
by intravenous infusions of [3,3,3-2H3]-leucine combined with ingestion of [1-13C]-
leucine intrinsically labeled casein as the sole protein source of the meal. Fat free
mass (ffm) was assessed by DEXA.

Results: After RYGB, basal plasma leucine concentration did not change, but
marked postprandial changes were seen: 1.7-fold increased peak concentrations
(217 [191,243] µmol/L, 377 [252,502], p=0.012) and 2-fold increased iAUC (4.1 [2.7,
5.5] mmol∙min/L, 9.5 [4.9, 14.2], p=0.03). However, the postprandial hyperleucinemia
was transient and concentrations were significantly below basal in the 4th hour.
Concentration differences were mainly caused by changes in leucine appearance
rate from orally ingested casein: Peak rate increased 3-fold (0.5 [0.4, 0.5] µmol/(kg
ffm∙min), 1.4 [0.8, 1.9], p<0.001) and time to peak was much shorter (173 [137, 209]
min, 65 [46, 84], p<0.001). Only minor changes were seen in endogenous leucine
release after RYGB.

Conclusion: RYGB accelerates protein digestion and amino acid absorption


resulting in faster and higher but more transient postprandial elevation of plasma
amino acids. Changes are likely mediated by accelerated intestinal nutrient entry and
clearly demonstrate that protein digestion is not impaired after RYGB.
WCIDT-0051
E-Poster Session

JNK INHIBITION RESTORES OBESITY-INDUCED ENDOTHELIAL DYSFUNCTION


MIMICKING THE VASOPROTECTIVE EFFECTS OF ROUX-EN-Y GASTRIC
BYPASS SURGERY
E. Osto1, P. Doytcheva2, T. Baechler3, E. Tarasco3, G. Pellegrini4, C. Matter2,
T. Lutz3, T. Luscher2
1
Center for Molecular Cardiology University of Zurich,
Center for Molecular Cardiology-Cardiology University of Zurich, Zurich, Switzerland
2
Center for Molecular Cardiology University of Zurich,
Center for Molecular Cardiology-Cardiology University of Zurich, Schlieren,
Switzerland
3
Institute of Veterinary Physiology- University of Zurich,
Institute of Veterinary Physiology- University of Zurich, Zurich, Switzerland
4
Institut für Veterinary Pathology- Laboratory for Animal Model Pathology,
Institut für Veterinary Pathology- Laboratory for Animal Model Pathology, zurich,
Switzerland

RYGB reduces cardiometabolic risk. We previously demonstrated that improved


endothelial-mediated vasorelaxation in diet-induced obese (DIO) rats 8 days after
RYGB was associated with reduced phosphorylation of JNK. Here we assessed
whether the in vivo inhibition of JNK activity in sham-operated rats (sham) mimics the
beneficial endothelial effects of RYGB. DIO rats undergoing RYGB were compared to
sham receiving vehicle (sham-V) or the unspecific JNK inhibitor SP600125
40mg/kg/day s.c. (sham-SP) for 8 days post-surgery. Second, sham rats received
control peptide TAT (sham-TAT) or the specific JNK peptide inhibitor D-JNKi-1
(sham-DJNK) for 8 days post-surgery. Thoracic aortic rings were isolated and
subjected to ex vivo isometric tension recordings. After submaximal contraction with
norepinephrine, cumulative relaxation responses were performed to GLP-1-(7–36)-
amide (10-12 to 10-6mol/L) or insulin (10-11 to 10-5mol/L). Western blot of JNK and
eNOS was performed on aortic tissue lysates. Body weight did not differ between
sham-SP and sham-V, while weight loss of RYGB was significant 8 days after
surgery. GLP-1- and insulin-induced vasorelaxation responses improved in RYGB
and showed a tendency for improvement in sham-SP compared to sham-V rats.
Sham-DJNK completely mimicked the effects of RYGB on endothelial function. JNK
protein phosphorylation was decreased and eNOS activation was increased in aortic
lysates of RYGB, sham-SP and sham-DJNK rats compared with respective controls.
We show a crucial role of JNK activation in obesity-induced endothelial dysfunction.
Chronic in vivo JNK inhibition mimics the endothelial protection of RYGB, suggesting
a novel JNK-dependent mechanism for the cardiovascular beneficial effects of RYGB.
WCIDT-0073
E-Poster Session

INCIDENCE AND PREDICTORS OF HYPOGLYCAEMIA AFTER LAPAROSCOPIC


SLEEVE GASTRECTOMY
L. Busetto, A. Belligoli, R. Serra, R. Fabris, C. Dal Pra', P. Fioretto, M. Sanna,
L. Prevedello, M. Foletto, R. Vettor
University of Padova,
Center for the Study and the Integrated Management of Obesity, Padova, Italy

Introduction: Hypoglycaemia is a known adverse event following gastric by-pass.


The incidence of hypoglycaemia after laparoscopic sleeve gastrectomy (LSG) is still
under investigation. The aim of our study is to verify the presence of OGTT-related
hypoglycemia after LSG and to identify any baseline predictors of its occurrence.

Methods: We analysed 66 consecutive non-diabetic morbid obese patients treated


with LSG. All patients were studied before and 12 months after LSG. Evaluation
included anthropometric parameters, 3-hour OGTT for blood glucose (BG), insulin
plasma levels, c-peptide, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and
highly sensitive C-reactive protein (hsCRP). Hypoglycaemia was defined as BG ≤ 3.3
mmol/L and severe hypoglycaemia as BG ≤ 2.7 moml/l.

Results: After surgery, 37/66 (56.1%) patients had one OGTT-related hypoglycaemia
and 15/66 (22.7%) had one severe hypoglycaemia. The highest frequency of
hypoglycaemic events and severe hypoglycaemic events occurred 150’ after load.
There were no baseline differences between patients with or without hypoglycaemia
in terms of age, BMI, waist, fasting glycaemia, HOMA-IR, glucose and insulin AUC,
total-cholesterol, triglycerides, IL-6 and hs-PCR. Before LSG, patients with
hypoglycaemia had higher levels of fasting insulin (p<0,05) and lower levels of blood
glucose 30-60 minutes after load (p<0.05), TNF-α (p<0.01), and HDL-cholesterol
(p<0.05). Independent predictors of the occurrence of an hypoglycaemia after surgery
were: low baseline blood glucose and TNF-α levels.

Conclusion: These findings confirm the high incidence of post-prandial


hypoglycaemia 1-year after LSG. Hypoglycaemic events are more frequent in
patients having lower glucose and TNF-α levels before surgery.
WCIDT-0114
E-Poster Session

REACTIVE HYPOGLYCEMIA (HYPO) AFTER RYGB IN TYPE 2 DIABETES


(T2DM)
M. Nannipieri
Santa Chiara University Hospital, Clinical and Experimental Medicine, Pisa, Italy

Background: Hypo is a complication of RYGB in non-diabetic subjects. In T2DM,


RYGB improves glucose metabolism, but whether this improvement is related to the
later development of Hypo is not known.

Aim: To investigate presence and mechanisms of postprandial Hypo in T2DM post-


RYGB.

Methods: 32 obese-T2DM subjects treated with RYGB received a 5-hr-OGTT before


and 12-18 months post-surgery. Insulin sensitivity was assessed by Matsuda-index
and ß-cell function by mathematical modelling analysis.

Results: Hypo occurred in 10 of 32 RYGB patients. Presurgery BMI was lower in


Hypo than non-Hypo (NH) (p=0.03), fasting glycaemia, mean plasma glucose, mean
insulin and insulin secretion rate were similar in both groups. Post-surgery, mean
insulin was reduced in both groups (p=0.003), whereas insulin secretion was
unchanged. Baseline insulin sensitivity was higher in Hypo than NH and post-surgery
it improved more in Hypo than in NH (4.3±2.3 vs 9.0±3.1 and 2.8±1.1 vs 5.5±2.6
mL.min-1.m-2,p=0.05). Baseline ß-cell glucose-sensitivity was similar in the two
groups (29±22 vs 25±34 pmol.min-1.m-2.mM-1); post-surgery increased more in Hypo
than NH (82±49 vs 34±23 pmol.min-1.m-2.mM-1, p=0.0018). Baseline insulin clearance
was similar, but post-surgery it improved in Hypo (p=0.004). No differences in
fasting/post-glucose GLP1 and glucagon were found between Hypo and NH; fasting
plasma PYY concentrations pre-surgery were significantly higher in Hypo compared
to NH (p=0.04). In logistic regression, pre-surgery insulin sensitivity and fasting PYY
were the only predictors of Hypo after surgery.
Conclusions: A better insulin sensitivity and higher fasting PYY concentrations
before surgery are associated with a higher risk of post-surgery Hypo in T2DM
subjects.
WCIDT-0078
E-Poster Session

IMPROVED GLUCOSE METABOLISM AFTER GASTRIC BYPASS. EVOLUTION


OF THE PARADIGM
D.J. Pournaras1, J. Nygren2,3, E. Hagström-Toft4, P. Arner4, C.W.(. Le Roux5,6,7,
A. Thorell2,3
1
The Norfolk and Norwich Oesophagogastric Cancer Centre,
Norfolk and Norwich University Hospital, Colney Lane, Norwich, UK
2
Department of Surgery, Ersta Hospital, Stockholm, Sweden
3
Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital,
Stockholm, Sweden
4
Department of Medicine, H7, Karolinska Institutet, Stockholm, Sweden
5
Diabetes Complication Research Centre, UCD Conway Institute,
School of Medicine and Medical Science, University College Dublin, Ireland
6
Department of Gastrosurgical Research and Education,
Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg,
Sahlgrenska University Hospital, Gothenburg, Sweden
7
Investigative Science, Imperial College London, UK

Aims/hypothesis

To quantify the relative contribution of calorie restriction, rerouting of nutrients and


adipose tissue reduction on improved glucose metabolism in type 2 diabetes after
Roux-en-Y gastric bypass (RYGB).

Methods

Fifteen diabetic patients, (47±9 years, BMI 41.3±4.2kg/m2) were randomised to a


two-week very low-calorie diet (VLCD) regimen or normal diet (ND) before RYGB. A
euglycaemic-hyperinsulinaemic clamp, indirect calorimetry and a standard meal test
were performed a) pre-diet, b) post-diet (preoperatively), c) two weeks and d) 12
months postoperatively. The primary outcome was M at two weeks postoperatively.

Results

In the VLCD group, after two weeks of calorie restriction M improved (2.9±1.3 to
4.2±1.1mg/kg/min, p=0.005) with no further change at two weeks postoperatively. In
the ND group two weeks postoperatively M was similar to the VLCD group (4.7±1.7
vs. 4.2±1.1, p=0.61). One year postoperatively M improved further in both groups.
The improvement in insulin-stimulated glucose uptake after VLCD and RYGB was
entirely accounted for by non-oxidative glucose disposal (NOGD), whereas weight
loss at one year postoperatively was associated with an increase in NOGD and
glucose oxidation. Postprandial glucose improved after VLCD (p<0.05) and even
more (p<0.05) two weeks after RYGB with no further change after one year.
Conclusion

Improved insulin sensitivity and postprandial glucose response occur early after
RYGB. Low calorie intake and rerouting of nutrients contribute through distinct
mechanisms. Weight loss contributes by increasing insulin sensitivity including
glucose oxidation and NOGD. These data suggest that combination of different
mechanisms is what makes RYGB an effective intervention for type 2 diabetes.
WCIDT-0157
E-Poster Session

BARIATRIC SURGERY IN PATIENTS WITH TYPE 1 DIABETES


A. Aminian1, S. Kashyap2, J. Kirwan2, B. Burguera2, P. Schauer1, S. Brethauer1
1
Cleveland Clinic, Bariatric and Metabolic Center, Cleveland, USA
2
Cleveland Clinic, Endocrinology and Metabolism Institute, Cleveland, USA

Introduction: There is a paucity of data on the impact of bariatric surgery in type 1


diabetes (T1D). The aim of this review was to quantify the overall effects of bariatric
surgery in obese patients with T1D.

Methods: We searched Pubmed, Scopus, ISI Web of Knowledge, and Google


Scholar from their inception to January 2015 to identify all relevant studies on
bariatric surgery in adult patients with T1D. Pooled mean of pre- vs. post-operative
glycated hemoglobin (HbA1C) were compared.

Results: The review included 16 studies with 105 individuals, including 10 case
series and 6 case reports. Overall, the dominant procedure was gastric bypass
(n=68, 65%). All studies reported a significant reduction in excess weight. A
significant reduction in weight-adjusted daily insulin requirements was shown in all
case series except one. Pooled mean±SD of pre- vs. post-operative HbA1C for the
whole cohort with available data (n=95) was 8.4±1.3 vs. 7.8±1.1%, respectively
(P<0.001). With inclusion of studies with average follow-up time of at least one year
(n=86), pooled mean±SD of pre- vs. post-operative HbA1C was 8.5±1.3 vs. 7.9±1.1 %,
respectively (P<0.001). In addition to common postoperative complications, profound
glycemic changes (diabetic ketoacidosis, and hypoglycemia) and GI dysmotility
symptoms (prolonged ileus, and acute gastric remnant dilation) have been reported.

Conclusion: Bariatric surgery leads to significant weight loss in severely obese


patients with T1D and results in significant improvement in insulin requirements and
glycemic status. The favorable metabolic effects of bariatric surgery may facilitate
medical management and cardiovascular risk reduction of T1D in the setting of
severe obesity.
WCIDT-0173
E-Poster Session

DOES ENDOSCOPIC DUODENAL-JEJUNAL EXCLUSION IMPROVE NON-


ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN PATIENTS WITH DIABESITY?
G. Sen1,2, R.S. Bajwa1, A.A. Roy3, D.B. Butler2, J. Ashmore2, R. Jain2, B. Hayee2,
S.A. Amiel2, R.E.J. Ryder1
1
Sandwell & West Birmingham NHS Trust, UK
2
King’s College Hospital London, London, UK
3
Barts Health NHS Trust, UK

Introduction: The increasing prevalence of NAFLD paralleling the diabesity


pandemic demands new effective therapies. The aim of this study was to investigate
the impact of an endoscopic duodenal-jejunal liner (endobarrier), with or without
additional glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy on NAFLD.

Methods: Adults with type 2 diabetes and obesity despite GLP-1RA therapy were
randomised to (1) endobarrier with GLP1-RA therapy (liraglutide); (2) endobarrier
alone; (3) escalated dose liraglutide (1.8 mg daily). Changes in weight, HbA1c and
non-invasive NAFLD scores (NAFLD fibrosis score (NFS) and AST to platelet ratio
index (APRI) score) were calculated over 3 months within groups. A sub-group
underwent MRI to evaluate hepatic fat fraction before and 4 months after endobarrier.
Hepatic fat fraction was calculated by 3 blinded independent assessors using 3
regions of interest. Descriptive statistics were performed, expressed as % frequency,
mean±SD or median (IQR).

Results: Of 40 patients (age 51.2±10.0 years, 40.0% male, 60.0% Caucasian,


baseline BMI 41.4±4.9kg/m2, HbA1c 78±16mmol/mol (9.3±1.4%)), 82.5% had a NFS
regarded as at intermediate (65.0%) or high risk (17.5%) for fibrosis. Over 3 months,
there was a reduction in weight by 7.3±4.0kg and in HbA1c by 14.5±15.3mmol/mol
(1.3±1.4%), P<0.0001. NFS reduced by 0.36(-0.1 to 1.0), n=15, P=0.04; 0.7(0.2 to
1.6), n=14, P=0.003; 0.2 (-0.1 to 0.8), n=11, P=0.14 in groups 1, 2 and 3 respectively.
APRI fell by 0.08(0.04 to 0.14), P=0.02 but was not significantly altered in groups 1 or
3. Of 8 patients undergoing MRI liver, there was a reduction in hepatic fat fraction
from 15.9±9.4% to 2.9±4.5% (P=0.0026).

Conclusion: Despite previous suboptimal response to GLP1RA therapy there was


improvement in NFS and APRI scores in those treated with endobarrier. Endobarrier
was effective at reducing hepatic fat fraction by 87.5±25.2%. These data suggest that
duodenal exclusion may be an effective future treatment for patients with NAFLD.
E-Poster Presentations

WCIDT-0047
Cost effectiveness of surgery as a treatment of diabetes

ONE YEAR METABOLIC OUTCOMES OF BARIATRIC SURGERY IN A MULTI-


ETHNIC ASIAN OBESE DIABETIC COHORT
Z. Zhiyan1, C. Khoo2, S.B. Jimmy3,4, L. Davide3,4, A. Shabbir3,4
1
Tan Tock Seng Hospital, Department of Surgery, Singapore, Singapore
2
National University Hospital, Department of Medicine, Singapore, Singapore
3
National University Hospital, Department of Surgery, Singapore, Singapore
4
National University of Singapore, Department of Surgery, Singapore, Singapore

Aim:

To determine ethnic differences in weight loss and glycaemic outcomes one year
after bariatric surgery in obese T2DM patients in Singapore.

Methods:

This was a single-centre, prospective cohort study conducted by the Department of


Surgery, National University Hospital, Singapore. We recruited 76 (47 females) type 2
diabetic patients who had BMI of ≥32.5kg/m2 between August 2008 and December
2013. The overall mean BMI was 42.4±8kg/m2, duration of diabetes 3 years and
preoperative HbA1c 7.8%. All patients underwent bariatric surgery and all had at
least 1 year complete follow-up data. 12 (52.2%) Chinese, 21 (70%) Malays and 14
(60.9%) Asian-Indians underwent laparoscopic sleeve gastrectomy (SG) and the
remaining laparoscopic Roux-en-Y gastric bypass (RYGB)

Results:

There were 23(30.2%) Chinese, 30(39.4%) Malays, and 23(30.2%) Asian-Indians.


The overall mean BMI was 42.4±8kg/m2. There were no ethnic differences in pre-
operative BMI, HbA1c, HOMA-IR and other metabolic co-morbidities. At 1 year post-
operation, 29 (44.6%) patients achieved complete DM remission (HbA1c<6.0%
without diabetes medication), 3 (4.6%) partial DM remission (HbA1c 6.1-6.4% without
diabetes medication), 26 (40%) improved, and the remaining 7 (10.8%) patients had
no change in the disease status. The proportion of insulin use reduced from 23%
preoperatively to 12% postoperatively, whereas the number of oral hypoglycemic
agents reduced from 1.4±1.0 preoperatively to 0.6±0.9 post-operatively. The means
change from pre-operative in the excess weight loss and HbA1c were similar
between the three ethnic groups. We observed no differences in the percent weight
loss (24.5±9.0 vs 25.2±7.4 kg) and post-operative HbA1c (5.9±0.9% vs 6.1±1.2%)
between SG and RYGB surgery.
Conclusion:

Both SG and RYGB surgery are effective in reducing excess body weight and
remitting diabetes among obese Asian with type 2 diabetes. Ethnicity does not
appear to influence the weight loss and glycaemic outcomes from bariatric surgery.
WCIDT-0057
Cost effectiveness of surgery as a treatment of diabetes

HOW EVOLUTION AND COMPARED ANATOMY GIVE SUPPORT METABOLIC


SURGERY? AN INTERDISCIPLINARY REVIEW
S. Santoro
Hospital Israelita Albert Einstein, São Paulo, Brazil

Introduction: Compared anatomy of the digestive tract of vertebrates provides


important information about how animals adapt to changes in their diet.

Objectives: To present a multidisciplinary data including evolutionary aspects of the


stomach and the gut and their adaptations to different diets and to introduce the
concept of surgical adaptation.

Method: A systematic review of the anatomy of the digestive tracts of primates, other
mammals and also other different living and extinct animals, confronting with their
natural diet. A review of compared gastric and intestinal Physiology, with a special
attention to the control of glucose blood levels.

Results: The confrontation of the caloric density and digestibility of different diets
among animals and their digestive anatomy suggests that in face of a continuous
enrichment of the diet (a diminution in the fiber with an enhancement of caloric
content) evolution tends to select shorter proximal guts and, as a consequence,
closer distal guts. Anthropological data confirm this observation among hominids in
the last 2.5 million years.

Conclusion: According to biological, evolutionary and functional studies, the many


models of metabolic surgery that result in a better metabolic control do have in
common some characteristics that make them adaptive procedures.
WCIDT-0058
Cost effectiveness of surgery as a treatment of diabetes

TRANSIT BIPARTITION: RESULTS SIMILAR TO A BPD, HOWEVER WITH


MINIMAL MALABSORPTION. LONG TERM FOLLOW-UP
S. Santoro1, C.E. Malzoni1, M.C.P. Velhote2, A. Lacombe1, C.G. Aquino1
1
Hospital Israelita Albert Einstein, Sao Paulo, Brazil
2
Hospital das Clínicas- University of Sao Paulo, Sao Paulo, Brazil

Background: In the last decade, it was discovered that the positive results of the
RYGB do not depend on caloric malabsorption. The positive results of a BPD may not
depend on malabsorption either.

Method: Since 2003,1337 patients were submitted to a sleeve gastrectomy (SG) and
Transit Bipartition (TB). A TB creates a gastro-ileal anastomosis in the antrum after
the SG; the nutrient transit to duodenum is much diminished as a significant part of it
goes to the ileum. A partial biliopancreatic bypass (BPD) is constructed. The stomach
remains with two exits. Jejunum is laterally anastomosed to ileum at 80 to 140 cm of
the ileocecal valve. The patients’ evolution data are registered using especially
designed in-cloud software.

Results: Average initial BMI is 41.3 and 29.9Kg/m2 after 10 years. EBMIL% was
93%, 91%, 84.9% and 75.5% respectively in the first, third, fifth and tenth year. T2DM
were present in 400 patients. Remission (Hba1c<6% without medication – protective
metformin excluded) in 260pts (86.7%); 38 pts (12.7%) improved and 2pts (0.7%) had
no response. Radiographies and cintilographies show nutrient transit mainly through
gastroileostomy. Three deaths occurred (0.2%). Other surgical complications were
5.5%, resolved without sequela. Signals of malabsorption are infrequent.

Conclusions: After a SG, TB is simple and easily revertible. It maintains the positive
results of a BPD however, avoiding blind loops and minimizing malabsorption,
diarrhea, flatulence. Weight and comorbidities are improved, similar to a BPD.
Diabetes is improved significantly without a complete duodenal exclusion. TB is an
excellent complement to a SG.
WCIDT-0109
Cost effectiveness of surgery as a treatment of diabetes

DEFINING AND DETERMINING VALUE FOR OBESITY SURGERY


R. Blackstone1, D. Haas2, R.C. Bay3, J. Crandall2, R.S. Kaplan2
1
Banner University Hospital- University of Arizona School of Medicine - Phoenix,
Department of Surgery, Phoenix, USA
2
Harvard Business School, N/A, Boston, USA
3
Arizona School of Health Sciences, Department of Interdisciplinary Health Sciences,
Mesa, USA

The study examined the relative value of Laparoscopic Sleeve (LSG) and Gastric
Bypass (LGBP) bariatric surgery. The patients in the LSG (n=69) and LGBP (n=89)
cohorts were similar; 58% had hyperglycemia. The LGBP cohort had more diabetic
patients (63% vs. 26%). We used Time-Driven Activity Based Costing to measure
the underlying costs (clinical and administrative personnel, supplies, space, and
equipment) incurred to perform LSG and LGBP operations by three surgeons who
practiced at one hospital. We found that LGBP and LSG procedures had similar pre-
op and post-op care costs, but LGBP procedures on average cost 19% more in total
due to higher operating room (OR) costs. OR supply costs were 26% greater for GBP
and non-supply costs were 87% greater for LGBP, due primarily to longer operating
times. The two procedures did not have statistically significantly different mortality
(none), complication, readmission, reoperation rates and weight loss at one year.
Both procedures demonstrated strong remission of hyperglycemia. The study data
indicates that LSG surgery is higher value due to producing similar outcomes at lower
costs than LGBP surgery for patients with hyperglycemia and Type 2 diabetes.
WCIDT-0164
Cost effectiveness of surgery as a treatment of diabetes

EVOLUTION OF HYPERTENSION IN OBESE DM2 PATIENTS WITH GASTRIC


BYPASS
P. Omelanczuk1, M. Sanchez1, M. Berducci1, N. Pampillon1, M. Abaurre1, A. Ojeda1,
V. Lasagni1, R. Palma1, S. Omelanczuk1, C. Penutto1
1
Hospital Italiano de Mendoza, Clinica Quirúrgica- Centro Quirúrgico de la Obesidad,
Mendoza, Argentina

Objective:

1. To evaluate the evolution of hypertension (HBP) in obese patients one year


after gastric bypass surgery.

2. To study the correlation between anthropometric variables/age and the


presence of hypertension one year after surgery.

Material and methods:

Patients included were 18 or older, had a BMI of ≥40, ≥35 and 30-35, and
comorbidities associated with obesity and diabetes. Demographic data (age, sex),
weight, BMI, comorbidities (HBP, dyslipedemia) and hypertension medication were
recorded pre and post-operatively.

Improvement or remission of hypertension was analyzed one year after surgery.


Links were studied between age and anthropometric variables (initial weight, initial
BMI, %EBMIL) at 6 and 12 months and the presence of HBP one year after surgery.

Qualitative variables are shown as percentages or proportions. The chi-square test


was used for tendencies and Fisher´s exact test for their analysis.

Quantitative variables are shown as mean ± standard deviation (SD) and were
analyzed using the Mann-Whitney U test. P ≤ 0,05 was considered statistically
significant.

Results:

Thirty-three DM2 patients with gastric bypass (GB) surgery were studied. Mean age
was 49,6 ± 8,4 years, and 63,6% (21 cases) corresponded to female patients. Mean
initial BMI was 48.3 ± 10.4. Prior to surgical treatment, 75.8% (25 patients) had HBP.
This percentage went down to 51.5% (17 patients) at 6 months and 39.3% (13
patients) at 12 months; p =0,003. Forty-eight percent showed remission of HBP. The
study of the association between anthropometric variables and HBP 12 months after
surgery showed that no patient with initial BMI≤ 35 (n:7) had HBP one year after
surgery vs 53.8% of patients with BMI ≥ 40 (p:0.027). 38.5% of patients with %EBMIL
lower than 50 still had HBP one year after surgery vs 15.4% with %EBMIL higher
than 65%.No correlation was found between age of onset (30 to 44; 45 to 54; > 55)
and the prevalence of HBP one year after surgery.

Conclusions:

Almost 50% of patients showed remission of hypertension one year after surgery.
Lower initial weight and higher EBMIL accounted for a reduction in the prevalence of
HBP one year after surgery. There was no correlation between age of onset and HBP
remission one year after surgery.
WCIDT-0165
Cost effectiveness of surgery as a treatment of diabetes

LIPID PANEL FOR DIABETES ONE YEAR AFTER SURGERY CONSIDERING


ADA OBJECTIVES
P. Omelanczuk1, M. Sanchez1, M. Berducci1, N. Pampillon1, M. Abaurre1, A. Ojeda1,
V. Lasagni1, R. Palma1, S. Omelanczuk1, C. Penutto1
1
Hospital Italiano de Mendoza, Clinica Quirúrgica- Centro Quirúrgico de la Obesidad,
Mendoza, Argentina

Hipothesis: Bariatric surgery causes improvement of the lipid panel in patients


submitted to this procedure.

Material and Methods: Retrospective observational study that included 36 morbidly


obese diabetic patients who were submitted to bariatric surgery, gastric sleeve (GS)
or gastric bypass (GBP). It was analyzed for each patient: insulinemy, glycemy,
HOMA index, glycated hemogoblin (HbA1c), total cholesterol, LDL, HDL, triglycerids,
basal weight (pre OP) and 1 year after surgery (post OP). For dislipdemia condition it
was considered after 1 year the category of improvement or remision of dislipidemia.
Remision of dislipidemia was defined by LDL and triglycerids values according to
standards for medical care in Diabetes-2014 (ADA) in diabetic patients without
hypolipemiant medication.

Results: 17 patients (47.2%) had GBP and 19 (52.8%) had GS. Average age was
47.8 ± 8.7 años and 77.8% (28 cases) were women. Preoperative BMI average was
44.84. Basal glycemy was 133.8 mg/dl ± 53.4 with significant decrease after 1 year of
surgery 77.9 ± 29.7 (p=0.0001). HOMA index was 5.9 ± 5.07 decreased to 2.26 ± 3.8
1 year after surgery (p =0.002).Basal LDL cholesterol was 125.28 mg/dl ± 20.9, 1
year after surgery 122.6 ± 39.6 (p= NS). Triglycerids decreased from 205.8 mg/dl ±
114.3 to 129.4 mg/dl ± 41.4 mg/dl (p= 0.002) 1 year after surgery. It was also
observed a minor increase in HDL from 44.7 ± 10.01 to 49.0 ± 11.2 (p= 0.006).
Remision of the disease was total in 16 patients (44.4%) and partial in 6 (16.7%) for
the population.Remision of dislipidemia for GBP was 82.3% vs 42.1% for GS p =
0.003. Patients submitted to GS had at pre OP an average of 44.7 mg/dl ± 10.8, 128
mg/dl ± 24.9 and of 189.1 ± 135.5 of HDL, LDL and Triglycerids respectively. A year
after surgery there were no significant changes in HDL (49.4 mg/dl ± 13.7), LDL
(138.9 mg/dl ± 44.1), and Triglycerids (140.2mg/dl ± 38.8) p= NS. Basal variables for
patients who had GBP were: HDL of 44.8 mg/dl ± 9.7; LDL 122.9 mg/dl ± 17.2;
Triglycerids 224.7 mg/dl ± 85. It was observed a post OP increase in HDL (48.4 mg/dl
± 7.2; p= 0.03), and a decrease in LDL (99.2 mg/dl ± 12.5; p= 0.06) and triglycerids
(115.2 mg/dl ± 42.8 p= 0.015) EBMIL was 68.42 ± 49.05 after 6 months and 76.55 ±
47.06 1 year after surgery.

Conclusions: One year after surgery it was observed a major percentage of


dislipidemia remision in morbidly obese diabetic patients. Remision was significantly
higher in patients submitted to Gastric Bypass.
WCIDT-0166
Cost effectiveness of surgery as a treatment of diabetes

NONALCOHOLIC FATTY LIVER DISEASE AND CARDIOVASCULAR RISK IN


MORBIDLY OBESE PATIENTS UNDERGOING BARIATRIC SURGERY
P. Omelanczuk1, M. Sanchez1, M. Berducci1, N. Pampillon1, M. Abaurre1, A. Ojeda1,
V. Lasagni1, R. Palma1, S. Omelanczuk1, C. Penutto1
1
Hospital Italiano de Mendoza, Clinica Quirúrgica- Centro Quirúrgico de la Obesidad,
Mendoza, Argentina

Introduction: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of


pathological conditions, ranging from simple steatosis to nonalcoholic steatohepatitis
and cirrhosis. Current evidence suggests that Obstructive Sleep Apnea (OSA) is a
potential candidate for progression NADFL in obesity. The NADFL, especially in its
worst forms, is linked to an increased risk of cardiovascular disease (CVD),
regardless of the underlying cardio-metabolic risk factors.

Aim: To assess non-alcoholic fatty liver disease and its relationship with OSA and
cardiovascular risk factors in morbidly obese patients undergoing bariatric surgery.

Materials and Methods: We studied consecutive morbidly obese patients


undergoing bariatric surgery. They were analyzed for each patient age, sex, weight,
BMI, waist circumference (WC) Neck circumference (NC), blood pressure (BP),
Charlson Comorbidity Score, the presence of DM, likely Syndrome Apnea Hypopnea
Obstructive Sleep (OSA) by STOP BANG, glycemia, insulinemia, HOMA, liver
function and liver biopsy. We used a NADFL Activity Score (NAS) to describe
Histology Activity Index (HAI) depending on the outcome of the Liver biopsy patients
were divided into two groups: severe liver disease (SLD) if they had severe steato-
hepatitis degree or fibrosis of any degree and mild liver disease (MLD). They were
compared with those who presented mild steatohepatitis, steatosis and normal
patients were included in this group Biopsy comparator in a second analysis.

RESULTS: We studied 65 patients with a mean age 43.04 ± 10.93, 52 were females
(70.27%). The Charlson Comorbidity Score was 2.78 ± 1.11, and the mean BMI of
45.35 ± 13.37. Laparoscopic Sleeve Gastrectomy (LSG) was performed in 45
patients (69.2%) and 20 patients (30.8%) underwent Ru-en-Y Gastric Bypass
(RYGB). Twelve patients (18.46%) had DM type II and insulin resistance in the
69.23%.The biopsy results were: steatosis in 3 patients (4.62%), Hepatitis Mild in 10
pts. (15.38%), severe hepatitis in 2 pts. (3.08%), fibrosis grade I in 26 pts. (40%),
Fibrosis grade II in 1 pt. (1.54%) Fibrosis grade III in 9 pts. (13.85%). In 13 patients
(20%) the biopsy was normal. The 56.9% (37 patients) were in SLD group, which had
differences with MLD group in terms to age, comorbidity, WC and NC, but were
statistically significant systolic blood pressure (SBP) and diastolic blood pressure
(DBP) 130.88 ± 18.81 vs. 121.48 ± 16.16 (p = 0.043) and 83.24 ± 9.76 vs. 77.63 ±
10.12; p=0.032 in SLD and MLD respectively. The 75.68% of patients had insulin-
resistance in SLD group, while in the MLD group was of 26.15%. The Insulinemia
(25.08 ± 37.15 vs. 17.74 ± 9.04) and HOMA (11.49 ± 7.47 vs. 4.15 ± 1.91) were
higher but without statistical significance in SLD group when compared with MLD
group, respectively. Also, the AST and ALT levels were higher in SLD group when
compared with MLD (23.90 ± 15.70 vs. 16.88 ± 7.51; p=0.010 and 34.43 ± 27.28 vs.
18.68 ± 8.82; p=0.001), respectively. Patients in SLD group had significantly more
often Bang Stop test high risk of OSA: 21 (56.7%) vs. 11 (42.3%); p=0.040. Finally
the 10-year cardiovascular risk measured by Framingham and UKPDS scores were
higher in SLD group: 4.03 ± 4.74 vs. 2.20 ± 2.69 (p = 0.014) and 6.24 ± 7.09 vs. 3.59
± 3.63 (p=0.011).

Conclusion: The greatest hepatocellular damage evidenced by biopsy and liver


enzymes was significantly associated with greater clinical Scores of OSA,
Hypertension, Diabetes and insulin-resistance and increased cardiovascular risk
scores to 10 years.
WCIDT-0168
Cost effectiveness of surgery as a treatment of diabetes

THE ECONOMICS OF BARIATRIC SURGERY FROM THE PERSPECTIVE OF A


PRIMARY CARE PHYSICIAN
R. Eliosoff
Ottowa, Canada

The enormity of the medical costs associated with the treatment of obese patients are
not sufficiently appreciated by most physicians or insurance providers. Several
comparative studies jncluding a long-term analysis of the SOS trial have suggested
that the costs of caring for an obese patient medically are roughly equivalent to the
costs of treating that patient surgically. In this presentation, I will argue that the costs
associated with bariatric surgery have plummeted in recent years, largely because of
a marked reduction in surgical complications while the costs of treating that same
patient medically actually have soared. This is a case based presentation from the
perspective of a primary care physician, in which I will argue that bariatric surgery
pays for itself very quickly. The cost savings come not only from the reduced
numbers of medications that patients are required to take after receiving a bariatric
surgical procedure, but also from the dramatically reduced numbers of medical
consultations, and diagnostic tests and procedures that are required to care for obese
patients. From an economic perspective, obesity is “the gift that keeps on giving” or
“the goose that lays the golden egg”.
WCIDT-0169
Cost effectiveness of surgery as a treatment of diabetes

EFFECT OF BARIATRIC SURGERY ON 948 CASES WITH DIABETES OR


IMPAIRED FASTING GLUCOSE: AN IRANIAN COHORT STUDY
A.R. Pazouki1, A. Kabir2, R. Riaz1, M.R. Abdolhossein1
1
Minimally Invasive Surgery Research Center, Iran University of Medical Sciences,
Tehran, Iran, Center of Excellence of European Branch of IFSO
2
School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran,
Iran

Background: Long life efficacy of bariatric surgery on cases with diabetes or


prediabetes is a matter of debate.

Methods: In this cohort study, between 2000 and 2015, 948 cases with
prediabetes/diabetes were evaluated among all 1932 cases under bariatric surgery in
Tehran, Iran.

Results: There were 785 females (82.8%). Fasting and non-fasting blood sugar and
lipid profile showed significant improvement during the time after surgery (P<0.001).
Most biochemistry indexes at four years have a return to their values at six months
after surgery but did not reach to their baseline levels.(Table 1) Excess weight loss
was dramatic (65%) at the first year follow up; while, decreased to 58% at fourth year.

Conclusion: Even though bariatric surgery has a significant positive effect on BMI,
blood sugar and lipid profile of cases with prediabetes/diabetes, and these effects are
persistent even after four years, the positive effect of the diabetic surgery decrease
gradually during the time. Long time studies are necessary.

Table 1 – Effect of Bariatric Surgeries on Anthropometric and Biochemistry Values of


Cases with Prediabetes/diabetes
WCIDT-0026
Effects of bariatric/metabolic surgery on diabetes-related complications

LAPAROSCOPIC SLEEVE GASTRECTOMY IMPROVES NONALCOHOLIC FATTY


LIVER DISEASE IN JAPANESE DIABETES PATIENTS WITH SEVERE OBESITY
A. Sasaki, H. Nitta, K. Otsuka, S. Baba, A. Umemura, T. Takahara, T. Iwaya,
S. Nishizuka, K. Koeda, M. Mizuno
Iwate Medical University Hospital, Surgery, Morioka- Iwate, Japan

Background: The aim of the present study was to evaluate the effects of
laparoscopic sleeve gastrectomy (LSG)-induced weight loss on nonalcoholic fatty
liver disease NAFLD in Japanese type 2 diabetes (T2DM) patients with severe
obesity.

Methods: Between June 2008 and April 2015, 52 Japanese patients with severe
obesity underwent LSG. Thirty patients had T2DM; 22 patients were taking oral
hypoglycemic agents and 12 patients were receiving insulin treatment. The first liver
biopsy was obtained intraoperatively and the second biopsy was performed for
nonalcoholic steatohepatitis (NASH) patients 6 months after LSG. All patients
underwent computed tomography before and 6 months after LSG, and visceral
adipose tissue (VAT) and liver volume were analyzed.

Results: At baseline, the mean age was 47 years and the mean BMI was 43 kg/m2.
The mean postoperative excess body weight loss at the time of the biopsy was 42%.
Resolution of T2DM was achieved in all 30 patients at 6 months after LSG. The mean
VAT was significantly decreased (294 vs. 145 cm2, p<0.001) and the liver was
significantly decreased at 6 months after LSG (2,247 vs. 1,673 mL, p<0.001).
Steatosis improved in all patients (from 27% to 8%). Seven of 10 patients with
inflammation at baseline showed improvement, and four of 10 showed less
ballooning. Four of 10 patients with fibrosis also showed improvement. No patient
experienced worsening of steatosis, inflammation, ballooning, or fibrosis.

Conclusions: LSG-induced weight loss results in significant improvement of liver


morphology in Japanese T2DM patients with severe obesity.
WCIDT-0031
Effects of bariatric/metabolic surgery on diabetes-related complications

ASSESSMENT OF DIABETIC MICROVASCULAR COMPLICATIONS 5 YEARS


AFTER BARIATRIC SURGERY
A. Humphreys1, S. Ravindra1, A. Miras1, L. Gerassimos2, S. Allen1, A. Ahmed1,
K. Moorthy1, S. Purkayastha1, T. Tan1, H. Chahal1
1
Imperial College NHS Healthcare Trust, Imperial Weight Centre, London,
United Kingdom
2
King's College Hospital NHS Foundation Trust, Princess Royal University Hospital,
London, United Kingdom

Background

Bariatric surgery has been shown to improve glycaemic control in patients with type 2
diabetes mellitus (T2DM). However, its medium-term effects on the microvascular
complications of T2DM remain unknown.

Objective

To assess the medium-term effects of bariatric surgery on nephropathy and


retinopathy in patients with T2DM.

Methods

Pre-operative and 5 year post-operative prospectively collected data were analysed


retrospectively for 62 patients with T2DM that underwent bariatric surgery at the
Imperial Weight Centre (gastric banding n=6, Roux-en-Y gastric bypass n=43, vertical
sleeve gastrectomy n=13) from 2006 to 2009. Nephropathy was assessed through
the mean of two urinary samples for albumin/creatinine ratio (ACR). Retinopathy
improvement or worsening was defined as a decrease or increase of at least two
steps in the Macular Oedema Disease Severity Scales respectively.

Results

ACR was significantly reduced from a median of 7.1 to 3.6 mg/mmol in the subgroup
of patients with pre-operative albuminuria (p=0.02), but not in the whole cohort
(p=0.48). In the group of 24 patients with available retinal images, retinal
appearances remained stable in 24, worsened in 5 and regressed in 6 patients.

Conclusions

Bariatric surgery had a beneficial effect on nephropathy at 5 years. Retinal


appearances stabilized or improved in the majority of patients, whilst the rates of
deterioration were not higher to those predicted from natural progression. Larger
randomized controlled trials are required to confirm our findings.
WCIDT-0054
Effects of bariatric/metabolic surgery on diabetes-related complications

GASTRIC BYPASS IMPROVES SUBCLINICAL NEPHROPATHY IN NON-


SEVERELY OBESE PATIENTS (BMI <35KG/M2) WITH TYPE 2 DIABETES
MELLITUS
A. Billeter1, S. Kopf2, B. Israel1, T. Schulte1, P. Knefeli1, M. Büchler1, P. Nawroth2,
B. Müller1
1
University of Heidelberg Hospital, Surgery, Heidelberg, Germany
2
University of Heidelberg Hospital, Internal Medicine I and Clinical Chemistry,
Heidelberg, Germany

Background

Bariatric surgery results in high remission rates of type 2 diabetes mellitus (T2DM) in
obese patients. We have previously shown that Roux-en-Y gastric bypass (RYGB)
improves diabetic neuropathy, likely due to a reduction in nitrosative stress. The
purpose of this study was to investigate whether RYGB is also able to improve
diabetic nephropathy.

Methods

Twenty patients (body mass index (BMI) between 26-35kg/m2) with poorly controlled,
insulin-dependent T2DM were enrolled. All patients were treated with a standardized
RYGB. Changes in serum creatinin levels, urinary albumin excretion and total serum
adiponectin were measured. High-molecular weight (HMW) adiponectin as a sensitive
marker for nephropathy was measured in serum and urinary samples using ELISAs.
Data are presented as mean ± SEM.

Results

Serum creatinin levels decreased within 3 months from 0.82 ± 0.05mg/dl to 0.67 ±
0.03mg/dl (p<0.05) and remained at these levels for 24 months. The urinary
albumin/creatinin ratio started decreasing within 3 months and reached significantly
lower levels after 6 months (2.38±0.86mg/mmol to 1.15±0.17mg/mmol, p<0.05).
Similarly, urinary HMW adiponectin decreased over the 24 month follow-up period
(0.19±0.07ng/ml to 0.07±0.01ng/ml, p<0.05). In contrast, total serum adiponectin
showed a significant increase over the same period whereas serum HMW
adiponectin did not change.

Conclusions

RYGB appears to improve microvascular complications of T2DM such as subclinical


nephropathy and neuropathy in non-severely obese patients. Further research should
investigate by which mechanisms diabetic nephropathy is improved in these patients.
WCIDT-0055
Effects of bariatric/metabolic surgery on diabetes-related complications

GASTRIC BYPASS IMPROVES STEATOSIS AND STEATOHEPATITIS IN


PATIENTS BMI <35KG/M2 WITH TYPE 2 DIABETES MELLITUS
B. Müller1, A. Billeter2, B. Straub3, B. Israel2, T. Schulte2, P. Knefeli2, P. Schirmacher3,
M. Büchler2, P. Nawroth4
1
University of Heidelberg Hospital, Heidelberg, Germany
2
University of Heidelberg Hospital, Surgery, Heidelberg, Germany
3
University of Heidelberg Hospital, Institute of Pathology, Heidelberg, Germany
4
University of Heidelberg Hospital,
Department of Internal Medicine I and Clinical Chemistry, Heidelberg, Germany

Background

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are
increasingly understood as related diseases. T2DM and NAFLD appear to propagate
each other and insulin resistance may be the pathogenetic link between these two
diseases. Bariatric surgery reduces steatosis, steatohepatitis and even fibrosis in
obese patients. The purpose of this study was to investigate whether RYGB in
patients with a body mass index (BMI)<35kg/m2 is able to improve liver damage in
diabetic patients.

Methods

Twenty patients (body mass index (BMI) between 26-35kg/m2) and poorly controlled,
insulin-dependent T2DM were enrolled. All patients were treated with a standardized
RYGB. Intraoperative and follow-up liver biopsies 36 months after RYGB were
histologically assessed by a pathologist using the NAFLD Activity Score (NAS).
Changes in liver function tests, glycemic control and insulin resistance using the
HOMA-model were determined preoperatively and after 36 months. Data are
presented as mean±SEM.

Results

BMI dropped from 32.80.5kg/m2 to 24.5±0.7kg/m2 (p<0.001) after 36 months.


Alanine-aminotransferase (ALT) and γ-glutamyl transferase (GGT) both significantly
improved over the 36 month follow-up period (ALT: 36.8±3.2U/l to 21.1±1.6U/l,
p=0.006; GGT: 55.2±9.7U/l to 22.1±5.2U/l, p=0.008) while Aspartate-transaminase
(AST) remained unchanged. Liver histology showed a significant reduction in
steatosis (39% to 11%, p=0.009 ) and NAS (4.0±0.2 to 1.0±0.23, p=0.008),
respectively. Insulin resistance also significantly improved (HOMA-IR: 19.2±2.8 to
4.9±0.8, p=0.004).

Conclusions
RYGB improves NASH and insulin resistance in diabetic patients with a BMI
<35kg/m2 significantly. Further research should investigate by which mechanisms
RYGB improves NAFLD and how these changes relate to T2DM.
WCIDT-0068
Effects of bariatric/metabolic surgery on diabetes-related complications

5-YEAR DRUG COSTS AFTER GASTRIC BYPASS IN PATIENTS WITH


DIABETES
G. Bruze
Clinical Epidemiology Unit, Department of Medicine, Stockholm, Sweden

Background

The economic effects of bariatric surgery in patients with diabetes are not well-
characterized. We aimed to assess changes in prescription drug costs over up to 5
years in this patient group.

Methods

In the Scandinavian Obesity Surgery Register (SOReg), we identified 5454 patients


with drug-treated diabetes who had gastric bypass between 2007 and 2012 (65%
women, mean age 46.8 years, mean BMI 42.3). For each surgery case, 10
comparators from the general population were identified and matched by age, sex,
and place of residence. Drug costs were retrieved from the nationwide Swedish
Prescribed Drug Register.

Results

The year before surgery, the mean annual drug cost was $1730 (median $1000).
Diabetes drugs made up 37% and cardiovascular drugs 13%. The mean annual 1-, 3-
and 5-year drug costs were $1193 (median $589), $1046 (median $398) and $1094
(median $387), corresponding to reductions of $532 (95%CI 490-575) at 1 year, $739
(95%CI 673-804) at 3 years, and $781 (95%CI 640-923) at 5 years. The greatest
contribution to drug cost reductions were from diabetes drugs at 1 (96%), 3 (74%)
and 5 years (65%). In general population comparators with diabetes (n=9642), drug
costs were $1394, $1424, $1273, and $1333 the year before the index date, at 1, 3
and 5 years. Diabetes drugs made up 30%, 31%, 33%, and 29% of these
costs, respectively.

Conclusion

Patients with drug-treated diabetes show substantial drug cost savings compared to
baseline over up to 5 years after gastric bypass, while costs in general population
comparators with diabetes were stable.
WCIDT-0082
Effects of bariatric/metabolic surgery on diabetes-related complications

ROUX-EN-Y GASTRIC BYPASS STIMULATES HYPOTHALAMIC MIR-122 AND


INHIBITS CARDIAC AND HEPATIC MIR-122 EXPRESSIONS
E. Ha
Keimyung University, Biochemistry- School of Medicine, Daegu, Korea

Background: microRNAs (miRNAs) are endogenous non-coding small ribonucleic


acids that have emerged as one of the central players of gene expression regulation.
This study was designed to determine and identify miRNAs that are associated with
Roux-en-Y gastric bypass (RYGB).

Methods: Male Sprague-Dawley rats were divided into two groups: sham and RYGB.
Changes in food intake and body weight were measured. miRNA microarray analyses
on the brain hypothalamus and heart were performed. The expressions of miR-122
were analyzed and the activities of AMP-activated protein kinase (AMPK) were
determined in the hypothalamus, heart, and liver. Antisense oligonucleotide (ASO)
miR-122 was transfected into hepatocellular carcinoma cells to validate in vivo
results.

Results: Body weights decreased in RYGB group compared with those in sham
group. Food intake was different between sham and RYGB groups. Of 350 miRNAs
that were investigated, we observed that miR-122, being predominantly found in the
liver, markedly increased (> 35-fold) in the hypothalamus and decreased (> 4-fold) in
the heart. Quantitative PCR analysis revealed that expression of miR-122 was
induced in hypothalamus but attenuated in the heart and the liver of RYGB group.
Activities of AMPK were decreased in the hypothalamus but increased in the heart
and liver. Knockdown of miR-122 in hepatocellular carcinoma cells stimulated
phosphorylation levels AMPK.

Conclusions: The results in this study suggest that RYGB regulates the expressions
of miR-122 in the hypothalamus, heart and liver, which in turn may modulate the
activities of AMPK, the master regulator of metabolism.
WCIDT-0089
Effects of bariatric/metabolic surgery on diabetes-related complications

DUODENAL-JEJUNAL BYPASS SURGERY ATTENUATES NONALCOHOLIC


FATTY LIVER DISEASE VIA DOWNREGULATION OF FATTY ACID SYNTHESIS
IN MICE
E. Ha1, T.K. Ha2
1
Keimyung University, Biochemistry- School of Medicine, Daegu, Korea
2
Hanyang Univ., General Surgery, Seoul, Korea

Background: Nonalcoholic fatty liver disease (NAFLD) is common among obese


subjects and its improvement after bariatric surgery has been reported. This study
aimed to determine the underlying mechanistic effect of bariatric surgery in mice

Methods: Mice were divided into four groups: normal chow diet (NCD) sham, high fat
diet (HFD) sham, HFD and weight matched follow-up (FU), and HFD duodenal-jejunal
bypass surgery (DJB). Changes in food intake and body weight were measured.
Peritoneal glucose tolerance test (PGTT) were determined before and after surgery.
Insulin tolerance test (ITT) was measured after surgery. Histological analyses were
performed. Gene expressions for fatty acid oxidation and synthesis were determined
by quantitative PCR and Western immunoblot analyses.

Results: Body weights decreased in DJB group compared with those in NCD and
HFD sham group. Food intake was not different between NCD and HFD sham and
DJB groups. PGTT after surgery revealed normal glucose response in DJB group and
delayed glucose response in FU group. ITT showed enhanced insulin sensitivity in
DJB group compared with that in FU group. Hepatic oil red O staining and triglyceride
measurement indicated that fatty changes in DJB group were significantly attenuated
compared with those in FU group. Quantitative PCR and Western immunoblot
analyses showed genes involved in the fatty acid synthesis were decreased in DJB
group while genes involved in the fatty acid oxidation were not changed.

Conclusions: The results in this study suggest that DJB attenuates NAFLD in mice
possibly via downregulation of genes in the fatty acid synthesis.
WCIDT-0115
Effects of bariatric/metabolic surgery on diabetes-related complications

WOULD END STAGE RENAL FAILURE PATIENTS ON RENAL DIALYSIS HAVE


REMISSION OF DIABETES MELLITUS AND RENAL FAILURE AFTER
BARIATRIC SURGERY?
A. Goralczyk, U. Parampalli, M. Adebibe, J. Dattani, G.N. Zumbadze, M. Plaha,
K. Devalia, K.R. Mannur
Homerton University Hospital NHS Foundation Trust, Bariatric Surgery, London,
United Kingdom

Introduction:

Bariatric surgery is known to improve diabetes mellitus (DM) and thereby reverse or
postpone the progression of chronic kidney disease (CKD). An ‘obesity paradox’ has
been reported in end stage renal failure (ESRD) patients where higher body mass
index (BMI) is associated with better survival. We share our experience of bariatric
surgery (BS) on ESRD patients.

Methods:

Data from ESRD patients on renal dialysis who underwent BS from 2008-2014 were
collected.

Primary outcomes were BMI, serum urea/creatinine/estimated glomerular filtration


rate (eGFR), diabetic remission or amelioration, morbidity and mortality.

Results:

Seven out of 2,589 patients were included, 5 had sleeve gastrectomy and 2 had
gastric bypass.

Mean pre-operative BMI was 47.74kg/m2 (range: 40-67), post-operative mean BMI is
31.41 kg/m2 (range 25-43.5), BMI reduction was 34%.

Renal function at >1 year follow-up showed improvement in serum urea and
creatinine was 47.8% and a deterioration in 57.2%. The eGFR improved in 42.8%,
deteriorated in 42.8%, was unchanged in 14.4%.

Five ESRD patients had concomitant DM (71.4%). Complete remission was seen in
60% and improvement in 40% (reduced diabetic medications).
Conclusion:

There was a significant BMI reduction in all patients with ESRD after BS. Diabetic
remission and improved renal function was seen in 60% and 47.8% respectively.
There was no reported mortality or morbidity which differed from other studies.

It is difficult to conclude from our small dataset that BS would be beneficial on ESRD
with DM. It is imperative that a multicentre study with up to 10 year follow up would
provide more meaningful information.
WCIDT-0132
Effects of bariatric/metabolic surgery on diabetes-related complications

THE INFLUENCE OF DIABETES AND MAJOR DEPRESSION ON CAROTID


INTIMA-MEDIA THICKNESS IN BARIATRIC SURGERY CANDIDATES
E. Bianciardi1, G. Di Lorenzo1, P. Gentileschi2,3, C. Niolu1,4, M. Cardellini1, F. Davato5,
A. Siracusano1,4, M. Federici1,5
1
University of Rome “Tor Vergata”, Department of Systems Medicine, Rome, Italy
2
University of Rome “Tor Vergata”,
Department of Experimental Medicine and Surgery, Rome, Italy
3
University Hospital "Fondazione PTV Policlinico Tor Vergata", Bariatric Surgery Unit,
Rome, Italy
4
University Hospital "Fondazione PTV Policlinico Tor Vergata",
Psychiatry and Clinical Psychology Unit, Rome, Italy
5
University Hospital "Fondazione PTV Policlinico Tor Vergata",
Center for Atherosclerosis, Rome, Italy

Introduction

Diabetes is a risk factor for atherosclerosis. One of the effects of diabetes is the
increase of carotid intima-media thickness (C-IMT), an early marker of
atherosclerosis. Although previous studies have associated major depression (MD)
with greater C-IMT no studies reported both diabetes and MD as risk factors for
atherosclerosis in obese individuals. The aim of this study was to investigate the
relation between MD and diabetes on IMT among bariatric surgery candidates.

Methods

Fifty-seven subjects [44w/13m; mean age (SD): 40.91 (10.62)] with severe obesity
[mean BMI (SD): 48.19 (7.02)] were enrolled. C-IMT was measured using Doppler
ultrasonography, from both carotid arteries. Oral Glucose Tolerance Testwas used to
identify subjects with normal or impaired glucose status. Past and current MD was
investigated with clinical interview performed by trained psychiatrist; the severity of
current MD was assessed with Hamilton Depression Rating Scale and Beck
Depression Inventory.

Results

ANCOVA models showed that the risk of diabetes was related to greater level of C-
IMT (p=.002) whereas the presence of lifetime or current MD didn’t influence C-IMT.
Interaction effects “diabetes × depression” weren’t significant. A secondary analysis
showed that lifetime MD (p=.04), but not current MD, was related to higher left carotid
C-IMT. Correlation analysis showed no relation between C-IMT and current MD
severity.
Conclusions

Present findings confirm the evidence that diabetes, but not MD, influence early
atherosclerosis markers in severe obese individuals. Future studies should address
about psychiatric comorbidities in regulating the risk of atherosclerosis in obesity.
WCIDT-0167
Effects of bariatric/metabolic surgery on diabetes-related complications

GASTRO INTESTINAL BY-PASS PATIENTS WITH DIABETIC FOOT


OSTEOMYLETIS: SELECTED ANTIBIOTHERAPY AFTER RADIO GUIDED BONE
BIOPSY SHOULD BE INTRAVEINOUS RATHER THAN ENTERAL
F. Mercier1, M. Lacomme1, K. Merah1, K. Mohammedi2, J.C. Dupre2, J.C. Labbe-
gentils3, C. Jaber.3
1
Hôpital Européen de Paris,Paris, France
2
AP HP Hôpital Bichat -
Claude Bernard Service d'Endocrinologie Diabète Nutrition et Maladies Métabolique
Paris France - INSERM U872 Paris, France
3
Hôpital Jean Verdier, Bondy, France

Oral antibiotherapy failure was observed in diabetic foot osteomyelitis (DFO) patients
with gastro intestinal bypass (GIBP) whereas success was achieved in others
diabetics patients without GIBP. DFO in our connected multi centers pratician
network, received antibiotherapy after radio guided bone biopsy (RGBB). Patients (n=
75), aged 44 to 92, were included from october 2013 to april 2015. All had a deficient
bone structure found on clinical or imaging basis. Local anesthesia (n= 28), loco
regional anesthesia (n=14) or no anesthesia ( n = 32) were proposed. GIPB was
found in 3 patients, being still diabetic with weight excess. We had no complication
and a 100 % success in bacterial retrieval.

Amoxicilin – clavulanate was given IV in first intention for all patients from PEDIS 2 to
4 or IDSA mild to severe, after debridment, while waiting for bacteria identification
and antibiogram, then we prescribed selected enteral antibiotherapy. Enteral relay
was ineffective when patients (n=3) had GIPB. We observed they went back to
PEDIS 4 or IDSA severe in less than 3 days. However the same antibiotic treatment
was effective IV via picc line or plain perfusion for 6 weeks.

Antibiotherapy was amoxicilin – clavulanate for MS Sath (n = 1) and Levofloxacine


for Pseudomonas (n = 2). Diabetic foot osteomyelitis best treatment is a prolonged
and evaluated antibiotherapy after radio guided bone biopsies (RGBB). Selected oral
antibiotherapy based on antibiogram should relay a probabilist
antibiotherapy. However long terme IV antibiotherapy should be discussed for patient
with GIBP.

Outcome of Diabetic Foot Osteomyelitis Treated Nonsurgically. A retrospective cohort


study, Eric Senneville Audrey Lombart, MD1,Eric Beltrand, MD2,Michel Valette,
MD1,Laurence Legout, MD1,Marie Cazaubiel, MD1,YazdanYazdanpanah,MD,PHD1
and Pierre Fontaine, MD,PH Diabetes Care 31:637-642, 2008

2. IDSA 2012 Infectious Diseases Society of America Clinical Practice Guideline for
the Diagnosis and Treatment of Diabetic Foot Infections Clinical Infectious Diseases
2012;54(12):132–1733.

Recommended standards for reports dealing with lower extremity ischemia: revised
version. Rutherford RB1, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones
DN. J Vasc Surg 2001 Apr;33(4):805.

Controversies in Diagnosing and Managing Osteomyelitis of the Foot in Diabetes


William J. Jeffcoate1 and Benjamin A. Lipsky2 Clin Infect Dis. (2004) 39 (Supplement
2): S115-S122.
WCIDT-0171
Effects of bariatric/metabolic surgery on diabetes-related complications

BARIATRIC AND METABOLIC SURGERY IN INDIA: A REVIEW


S. Ikramuddin1, S. Agarwal2
1
Department of Surgery, University of Minnesota, Minneapolis, MN, USA
2
Healthcare Economics, Medtronic, Dublin, Ireland

Introduction: Genetic predisposition, adiposity, economic growth, urbanization and


globalization have contributed to increase in incidence of obesity and Type 2
diabetes. Surgery as an option to treat the underlying obesity and diabetes have
gained popularity. We review the evidence evaluating the effectiveness of surgery in
the Indian population.

Methods: We reviewed data on Medline until June 2015. “Bariatric Surgery” and
“India” were used as search terms. Titles and abstracts were systematically reviewed
and analyzed.

Results: The majority of the papers described the surgical technique or included
case series that followed patients over 1-5 years post-surgery. Comorbidity resolution
especially Type 2 diabetes was the key focus. Most of the papers studied
laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. One
study (Lakdawala et al.) evaluated the effectiveness of gastric bypass over a 5 year
period in patients with BMI 30-35 kg/m2 and Type 2 diabetes. IFSO Asia Pacific
Chapter consensus statement from 2011 recommended the consideration of bariatric
surgery for those with a BMI ≥ 30 and inadequately controlled T2D.

Conclusion: Prospective, short term case series and society consensus statements
highlight the effectiveness of bariatric and metabolic surgery. Further long term,
comparative data are required to eliminate barriers in access to optimal care for
metabolic disease.
WCIDT-0172
Effects of bariatric/metabolic surgery on diabetes-related complications

REVIEW OF COST EFFECTIVENESS STUDIES ON BARIATRIC SURGERY


S. Ikramuddin1, S. Agarwal2
1
Department of Surgery, University of Minnesota, Minneapolis, MN, USA
2
Healthcare Economics, Medtronic, Dublin, Ireland

Objective: Given the increasing focus on healthcare costs and need for cost-
effectiveness information, we sought to review the literature for cost effectiveness
studies on bariatric surgery.

Methods: We reviewed data from Medline January 2005 through June 2015.
Bariatric Surgery, Diabetes, and Cost were used as search terms. Titles and
abstracts of 171 articles were systematically reviewed and analyzed. Additional target
search was performed. 18 studies were included in the final review.

Results: 8 studies reviewed European data, 7 studies reviewed US data, and 1 study
each originated from Brazil, Mexico and South Korea. Most studies evaluated data
from a healthcare system or payer perspective. Incremental-Cost-Effectiveness-
Ratios (ICERs) showed surgery was cost saving in Austria, Italy, Germany and
France, in terms of Quality-Adjusted-Life-Years gained compared to conventional
treatment. ICERs showed surgery was cost-effective in US, UK, Spain, Finland,
South Korea and Sweden. Younger, women, non-whites, higher BMI (40+), obesity
related diseases (particularly type 2 diabetes), lower duration of existence of
comorbidities, laparoscopic approach were associated with better ICERs. Surgery
extended life expectancy by about 2-3 years. Studies also reported increase in tax
collection (sick leave and unemployment reduction by ~18%, productivity increase of
57% for self-employed).

Conclusion: Data from studies across different countries and healthcare systems
point to cost-effectiveness of bariatric surgery compared to conventional treatment.
Degree of cost effectiveness is greater in severe, vulnerable and early intervention
populations. Access to surgery in the appropriate population should be prioritized as
it is associated with economic and productivity benefits.
WCIDT-0175
Effects of bariatric/metabolic surgery on diabetes-related complications

INCREASED BUTYRYLCHOLINESTERASE ACTIVITY ARE ASSOCIATED WITH


OBESITY AND DIABETES AND S100B ELEVATED IN OBESE T2DM SERUM
DECREASED AFTER BARIATRIC SURGERY
R.M. Guaragna1, F. Rohden1, F. Schmidt1, N. Coimbra Scaglia2, A. Wyse1,
A. Padoin2, C. Cora Mottin2
1
Departamento de Bioquímica,UFRGS, Porto Alegre, RS, Brazil
2
Centro de Obesidade e Síndrome Metabólica, Hospital São Lucas, PUCRS,
Porto Alegre, RS, Brazil

The increase in blood glucose, dyslipidemia and hypertension are risk factors that
increase chronic inflammation and vascular endothelium dysfunction in type 2
diabetes mellitus (T2DM). Many studies suggest the involvement of acetylcholine
(ACh) in the inflammation through the “cholinergic anti-inflammatory pathway”.
Butyrylcholinesterase (BuChE) found in serum, pancreas, liver, and SNC, have been
considered regulators of inflammation since they control ACh action and
consequently the release of peripheral cytokines. S100B is a secretory protein which
is implicated in the regulation of glucose metabolism and stimulates the expression of
proinflammatory cytokines. In this study we measured the BuChE activity and S100B
levels in a serum samples of health subjects (n=10) and patients non obese (NOB)
with T2DM (n=5) and obese (OB) NDM2 (n=12) and T2DM (n=17) undergoing
bariatric surgery (COM/PUCRS, Brazil). S100B serum was detected by ELISA kit.
BuChE activity was determined by Ellman method. Protein was measured by
Bradford method.

The BuChE activity (expressed in µmol ACSCh/h/mg protein) when compared with
NOB NDM2 (0.88±0.04) increased significantly in NOB T2DM (1.14±0.09) or OB
NDM2 (1.14±0.07) or OB T2DM (1.12±0.06). The level of S100B protein expressed in
serum (pg/mL) increased significantly in T2DM (71.3±8.3), when compared with
NDM2 (47.2±6.4). However, S100B serum decreased in OB T2DM (28.4±5.4) one
year after bariatric surgery.

In our patients, BuChE activity and S100B levels may be associated with low-grade
inflammation. S100B can be used as an inflammatory biomarker of diabetes.
Furthermore, decreased S100B serum levels may be associated with metabolic
outcome of this disease after surgery.
WCIDT-0022
Epidemiology and economic impact of diabetes

TYPE II DIABETES MELLITUS AND CARDIOVASCULAR RISK AMONG


MEXICAN CHILDREN WITH OBESITY IN A ELEMENTARY SCHOOL IN MEXICO
CITY
H. Ortiz-Perez1, I. Martinez-Barbabosa1, R. Cordova-Moreno2, M. Aguilar-Venegas1
1
Universidad Autónoma Metropolitana - Xochimilco,
Departamento de Atención a la Salud, Mexico City, Mexico
2
Universidad Autónoma Metropolitana - Xochimilco,
Departamento de Sistemas Biológicos, Mexico City, Mexico

Introduction: Mexico ranks first global place in overweight and obesity in


schoolchildren. The combined national prevalence of overweight and obesity
(National Survey of Health and Nutrition, 2012), using the WHO criteria, was 34.4%
among children (5-11 years), and 38.8% of overweight and 32.4% obesity among
adults (20+ years). Type 2 Diabetes Mellitus (T2DM) is the leading cause of death
among adults (20+ years) with a rate of 72.7 per 100,000 inhabitants (2012).

Objective: To identify the cardiovascular risk among children and his association
with the family history of chronic diseases (FHCD).

Material and methods: Cross-sectional study. A total of 222 children (108 females
and 114 males) aged 8 to 12 years, from a school in Coyoacan, Mexico City, were
studied. Children underwent anthropometric evaluation (weight, height, and
abdominal circumference) and BMI was estimated. Among children with BMI ≥ 30, a
questionnaire about FHCD was applied to his parents.

Results: Of the 222 children, 42 (18.9%) were overweight, and 37 (16.7%) were
obese, both figures more than national prevalence. The most prevalent risk factors
among children with obesity was abdominal circumference ≥90th percentile (88%),
and more than half of the children (51.6%) cardiovascular risk were evaluated
according to the criteria MIRACLE.

Conclusion: An increased prevalence of overweight and obesity, together with high


cardiovascular risk were observed in children, contributing to the onset of Metabolic
Syndrome and T2DM at younger ages. It is urgent to implement childhood obesity
prevention programs.

Keywords: Type II diabetes mellitus; Overweight and Obesity; Cardiovascular Risk;


Children; Mexico
WCIDT-0117
Epidemiology and economic impact of diabetes

STATISTICAL STUDY EXAMINING THE RELATION BETWEEN PREVALENCE OF


DIABETES AND FOOD INSECURITY IN THE UNITED STATES
G. Schur
Concord, USA

A statistical analysis of counties across the United States with a diabetes rate above
the national average investigates the correlation between food insecurity and
diabetes prevalence. The Centers for Disease Control (CDC) reports yearly county-
level diabetes prevalence; based on this data, the national mean age-adjusted
diabetes prevalence in 2012 was 11.27%. The mean age-adjusted diabetes
prevalence for all counties with diabetes rates above this average (n=1468) was
13.15%. Based on county-level data acquired from Feeding America, the average
national food insecurity in 2012 was 15.9%. The overall average food insecurity rate
for counties with diabetes rates above 11.27% was 16.47%. Counties with diabetes
prevalence between 11.27%-13% had a mean food insecurity of 15.18%, while
counties with diabetes prevalence between 13%-15% had a mean food insecurity of
17.1%, and counties with diabetes prevalence above 15% had a mean food
insecurity of 21.15%. This increasing trend indicates that counties that have a high
diabetes rate tend to be food insecure, demonstrating a correlation between the
prevalence of food insecurity and diabetes that is further examined in this study. Food
insecurity therefore may be a relevant contributing factor to the high prevalence of
diabetes in the United States.
WCIDT-0137
Epidemiology and economic impact of diabetes

EXPLORING INEQUALITIES IN DIABETES CARE FOR OLDER SOUTH ASIAN


PEOPLE IN THE UK: A REALIST REVIEW OF THE LITERATURE
E. Wilkinson, M. Waqar, G. Randhawa
University of Bedfordshire, Institute for Health Research, Luton, United Kingdom

Complications of diabetes unequally affect particular groups in our society and older
people and people with a South Asian background are two population groups with
increased risk whose numbers will grow in the future. We explored the evidence
about diabetes care for older people with South Asian ethnicity to understand the
contexts and mechanisms behind interventions to reduce inequalities.

We used a realist approach to review the literature, mapped the main areas where
relevant evidence exists and explored the concepts and mechanisms which underpin
intervention. From this we constructed a theoretical framework for a programme of
research and put forward suggestions for what our analysis might mean to providers,
researchers and policy makers.

There was a dearth of studies with specific focus on diabetes care for older people
with South Asian ethnicity in the UK, despite their higher risk and policies for
individualised and culturally sensitive care. South Asians experience diabetes ten
years earlier than White Europeans and are heterogeneous group who should be
targeted for early intervention and research into ageing and cultural influences in
diabetes prevention and care.

Broad themes of cultural competency; co morbidities and stratification; and access


emerged as mid-level mechanisms which have individualised, culturally intelligent
and ethical care at their heart and through which inequalities can be addressed.
These provide a theoretical framework for future research to advance knowledge
about concordance; culturally meaningful measures of depression and cognitive
impairment; and care planning in different contexts which support effective diabetes
care for aging and diverse populations.
WCIDT-0154
Epidemiology and economic impact of diabetes

CANDIDAL COLONIZATION, STRAIN DIVERSITY AND SALIVARY PH AMONG


SUBJECTS WITH TYPE II DIABETES MELLITUS
A. Monea1, A.C. K.-Ivacson2, G. Beresescu3
1
Tg.Mures, Romania
2
University of Medicine and Pharmacy Tg.Mures,
Department of Odontology and Oral Pathology, Tg.Mures, Romania
3
University of Medicine and Pharmacy Tg.Mures,
Department of Tooth Morphology and Dental Materials, Tg.Mures, Romania

Oral candidiasis is a common opportunistic infection of the oral cavity. Our objective
was to evaluate the prevalence of Candida in the oral cavity of diabetics, and of the
influence of local and systemic factors on candidal colonization. 41 subjects with type
2 diabetes mellitus and 35 healthy subjects were included in the study. From each
individual oral rinse samples were taken, inoculated on Sabouraud dextrose agar with
chloramphenicol plate and incubated at 370 for 24 h. The growth of Candida was
identified by smooth, white or creamy colored buttery colonies. The candidal isolates
were identified and density was expressed in the number of colony-forming units
(CFU) per mL of oral rinse. Salivary pH was determined using pH strips. The
relationship between specific host factors and candidal colonization was also
investigated.The mean values of CFU of Candida found in diabetics were significantly
higher than in healthy controls. Candida albicans was the most frequently isolated
species, but diabetics had a variety of other candidal species present. Salivary pH
was significantly decreased in diabetics versus controls. Although there was a
significant positive correlation between glycemic control and candidal colonization in
type 2 diabetics, there was a negative correlation between salivary pH and candidal
carriage in type 2 diabetics.Diabetic patients not only had a higher candidal carriage
rate, but also a variety of candidal species. Oral candidal colonization was
significantly associated with glycemic control and salivary pH. Acknowledgement:
internal research grant no.1064/26.01.2015 financed by SC COSAMEXT SRL
Tg.Mures and developed by UMF Tg.Mureş.
WCIDT-0036
Impact of bariatric/metabolic surgery on cardiometabolic risk

LONG-TERM IMPROVEMENT OF CARBOHYDRATE PARAMETERS AFTER


GASTRIC BYPASS (IN CASES OF SEVERE OBESITY)
S. Gomez-abril1, M. Rocha2, C. Morillas-Ariño3, J.L. Ponce-Marco4, A. Hernandez-
Mijares3, T. Torres-Sanchez5, F. Delgado-Gomis5
1
University Hospital Dr Peset. School of Medicine. University of Valencia. Spain,
Department of General and Digestive Surgery., Valencia, Spain
2
University Hospital Dr Peset. Valencia. Spain, Service of Endocrinology-
Foundation for the Promotion of Health and Biomedical Research in the Valencian R
egion FISABIO, Valencia, Spain
3
University Hospital Dr Peset. School of Medicine. University of Valencia. Spain,
Service of Endocrinology, Valencia, Spain
4
University Hospital La Fe. School of Medicine. University of Valencia. Spain,
Department of General and Digestive Surgery, Valencia, Spain
5
University Hospital Dr Peset. Valencia. Spain,
Department of General and Digestive Surgery, Valencia, Spain

Objective:

The long-term effects of bariatric surgery on carbohydrate metabolism parameters


have not been studied in depth. This study was to assess long-term changes in
metabolic parameters following a gastric bypass.

Methods:

Ninety patients with severe obesity were recruited between 2006 and 2009 (74 were
women). The subjects’ weight, BMI, percentage of excess weight loss (%EWL),
fasting glucose and insulin, HOMA-IR, A1c were determined at recruitment and 1, 2
and 5 years post-surgery. We also determined C3 fraction of complement (C3c) and
sex hormone-binding globulin (SHBG) which recently have been involved in insulin
resistance.

Results:

Patients were 42.5+9.7 years old. Anthropometrical parameters were reduced


following surgery but a slight recovery was detected after 5 years. Despite this, there
was a long-term improvement of carbohydrate parameters without significant
variation.

Surgery Year 1 Year 2 Year 5 p value


Carbohydrate metabolism parameters
Glucose (mg/dl) 112±86a 91±11b 90±13b 88±12b <0.001
A1c (%) 5.96±0.98a 5.34±0.48b 5.40±0.37b 5.40±0.42b <0.001
Insulin (mU/ml) 20.0±14.7a 6.40±2.81b 6.46±3.01b 7.17±3.50b <0.001
HOMA-IR 5.64±4.66a 1.47±0.79b 1.47±0.84b 1.60±0.94b <0.001
C3c (mg/dl) 140±20.9a 104.6±19.9b 106.9±21.5b 104.9±19b <0.001
SHBG (nmol/L) 46.5±25.0a 83.5±44.7b 90.2±52.1b 84.9±52.6b <0.001

Data are presented as mean±standard deviation. Different superscript letters (a,b,c)


show statistical differences between groups when compared by one way ANOVA.

Conclusions:

A significant long-term improvement of carbohydrated parameters linked to obesity is


achieved in gastric bypass patients despite a slight regaining of weight in the long-
term. This is the first study to show that insulin resistance is associated through long-
term improvements in parameters such as SHBG and C3c.
WCIDT-0044
Impact of bariatric/metabolic surgery on cardiometabolic risk

IMPACTS OF BARIATRIC SURGERY ON BEHAVIOURAL AND FREE-LIVING


PHYSICAL ACTIVITY FACTORS RELATED TO REDUCTIONS IN CARDIO-
METABOLIC RISK: A MIXED-METHODS STUDY
S. Hanley
Swansea University, Swansea, United Kingdom

Aim: To explore perceptions of readiness for exercise and physical activity (PA)
engagement in patients before and after bariatric surgery.

Methods: With service delivery approval, 24 patients were recruited. Participants


were allocated into three groups: a) pre-surgery patients that fulfilled rationing criteria
based on modified Swansea-DUBASCO scores; b) patients between 9 and 24
months post-surgery; c) post-surgery patients greater than 5 years. Participants
completed a semi-structured interview that explored experiences of diet, physical
activity and quality of life. Participants were also given a 3-dimensional accelerometer
fitness wrist band to record free-living PA patterns over a 7-day period. Interview data
were transcribed verbatim and analysed using interpretive thematic analysis. PA data
were analysed using SPSS with significance accepted as P<0.05.

Results: Thematic analysis highlighted shared and independent experiences across


different groups. Pre-surgery patients discussed extensive barriers to engagement in
PA and triggers that either enhanced or decreased activity levels. Post-surgery
patients perceived improvements in their quality of life and desires to engage in PA
following surgery. However, these improvements were tempered by difficulty in
adjusting to rapid weight loss, ingestion of food and digestive upset and poor body
image associated with excess skin folds. Pre-surgery, PA data revealed significant
shortfalls from UK Department of Health PA guidelines. This was still evident in some
post-surgery patients, however the ‘fitness gap’ was reduced in magnitude.

Conclusion: Findings illustrate improvements in readiness to exercise and objective


markers of PA that are strongly related to factors that improve cardio-metabolic risk
profile of post-bariatric surgery patients.
WCIDT-0052
Impact of bariatric/metabolic surgery on cardiometabolic risk

METABOLIC CHANGES AFTER ROUX-N-Y BARIATRIC SURGERY IN


HISPANICS
P.I. Altieri1, J. Hernández-Gil de Lamadrid1, J.J. Nieves-Rivera1, L. Mora1,
L. Corretjer1, A. Suárez1, H.L. Banchs1, J. Muñiz1, N. Escobales1, M. Crespo1
1
University of Puerto Rico, Departments of Medicine-Surgery-Physiology, San Juan,
Puerto Rico

Background and Objectives: Describe the metabolic outcomes 12 months after


bariatric surgery (Roux-N-Y) in morbidly obese Hispanic patients, and evaluate the
correlation between weight loss and the observed changes.

Subjects/Methods: Medical records from a hundred-and-two Hispanic obese


patients who underwent bariatric surgery were analyzed. The following variables were
obtained before and 12 months after surgery: Body Mass Index (BMI), body weight,
total cholesterol (TC), triglycerides, high density lipoprotein (HDL), low density
lipoprotein (LDL), and fasting blood sugar (FBS).

Results: Ninety-seven percent of patients underwent Roux-N-Y surgery; 79.4% were


females and 44% were diabetics. We observed statistically significant reductions
(p<0.05) 12 months after surgery in: BMI -14.3(±6.2) kg/m2, weight -86.1(±34.4) lbs,
TC -17.9(±32.4) mg/dL, triglycerides -28.7(±40.6) mg/dL, LDL-15.4(±30.6) mg/dL, and
FBS -11.3(±23.5) mg/dL. HDL increased +5.22(±12.9) mg/dL (p<0.0006). The
correlation between weight loss and changes in FBS, Cholesterol, HDL and LDL
fluctuated between .1-0.5 (P.>0.05). The sleeve surgery showed a lower correlation
than Roux-N-Y between weight loss and FBS and no change in HDL, LDL and total
cholesterol (P.>.05).

Conclusion: Gastric bypass surgery of the Roux-N-Y significantly improves the lipid
profile and FBS levels in obese Hispanic patients, but not with sleeve surgery. The
poor correlation factor between weight loss and these variables suggests that other
mechanisms, independent from weight loss are responsible for these changes.
WCIDT-0102
Impact of bariatric/metabolic surgery on cardiometabolic risk

HIGH-SENSITIVITY C-REACTIVE PROTEIN LEVELS DO NOT PREDICT WEIGHT


LOSS RESPONSE TO BILIOPANCREATIC DIVERSION WITH DUODENAL
SWITCH AND RESOLUTION OF TYPE 2 DIABETES
A. Tchernof1, M. Nadeau1, L. Biertho1, S. Biron1, F.S. Hould1, S. Marceau1,
M.C. Vohl2
1
Quebec Heart and Lung Institute, Obesity Axis, Quebec City, Canada
2
Laval University, School of Nutrition, Quebec City, Canada

Background: We tested the hypothesis that circulating inflammatory marker C-


reactive protein (CRP) predicts weight loss and resolution of type 2 diabetes following
biliopancreatic diversion with duodenal switch (BPD-DS).

Methods: Pre-surgery plasma CRP level measurements were available for n=388
patients with 5-year weight loss data. CRP levels were analyzed in tertiles since
distribution was non-normal. In a second analysis, patients were matched for sex and
initial BMI across CRP tertiles (n=84/group).

Results: Patients in the upper tertile of circulating CRP levels at the time of surgery
were characterized by significantly higher BMI than those in the lower CRP tertile
(54.3 vs. 49.8 kg/m2, p<0.0001). In terms of weight loss, high CRP levels were
associated with lower excess weight loss (EWL) at 3 and 6 months (p<0.02 for both),
but not at subsequent time points up to 5 years. The number of diabetic patients was
similar among patients separated into CRP tertiles (p=0.62), and rates of diabetes
resolution were also similar (p=0.81). In repeated measures analyses, weight, BMI
and EWL trajectories were not significantly different across CRP tertiles. When
matched for sex and initial BMI, identical body weight, BMI and EWL were observed
in all three CRP groups despite highly significant differences in CRP levels. Rates of
type 2 diabetes resolution were identical among groups (p=0.32).

Conclusions: Although high circulating levels of inflammation marker CRP relate to


high BMI at surgery, they do not predict weight loss and diabetes resolution
associated to BPD-DS over 5 years after control for initial BMI.
WCIDT-0116
Impact of bariatric/metabolic surgery on cardiometabolic risk

DECREASED CARDIOVASCULAR RISK FACTORS (CVRF) AFTER METABOLIC


SURGERY (MS) IN MORBID OBESE PATIENTS: LONG TERM FOLLOW UP (FU)
(6 TO 13 YEARS)
S. Faria1, O. Faria1, L. Berber1, M. Facundes1, R. Cohen2
1
Gastrocirurgia de Brasília, Bariatric Surgery, Brasilia, Brazil
2
Oswaldo Cruz German Hospital, The Center for Obesity and Diabetes, Sao Paulo,
Brazil

Previously, MS meant low BMI surgery. Metabolic outcomes should be considered in


any BMI, and the duration of effects on CVRF assessed.

The primary endpoint was to determine the duration of Roux-en-Y gastric bypass
(RYGBP) effects on CVRF: glycated hemoglobin (HbA1c), fasting plasma glucose
(FPG), fasting insulin, triglycerides (TGL), LDL, HDL, total cholesterol, blood pressure
(BP) and weight loss (WL).

Retrospectively, 78 postoperative patients underwent surgery and had 6 to 13 years


FU. The above-mentioned CVRF and the use of diabetes medication were analyzed.
Type 2 Diabetes Mellitus (T2DM) remission criteria followed the 2009 Diabetes Care
paper by Buse.

37.2 % had up to 13 years FU and 62.8% had 6 to 9 years. 50.7% used at least one
T2DM drug. All CVRF decreased and WL was sustained during FU and HDL was
higher than baseline. Higher %WL correlated to lower LDL, higher HDL and lower BP.
Regarding remission, 77% had complete and 5% partial remission .Only 7.6 %
presented no change (10.4% no data). Greater WL led to decreased CVRF. Within
the 6 recurrences most sustained longterm WL, 4 in 6 used insulin and were
operated with baseline HbA1c above 10%. Both are known factors associated to
longterm T2DM recurrence.

RYGB is a remarkable tool for sustained T2DM control reinforcing the role of MS
regardless of baseline BMI. WL was key for positive longterm outcomes.

MS has a durable effect on T2DM with low recurrence, Major CVRF are decreased
and its longterm effects seem to be related to sustained WL.
WCIDT-0110
Impact of bariatric/metabolic surgery on glycemic control

EFFECT OF ROUX-EN-Y GASTRIC BYPASS ON PREDIABETES AND DIABETES


IN SEVERELY OBESE ADOLESCENTS IN SWEDEN AND THE USA
A.J. Beamish1,2,3, T. Olbers1,2, E. Gronowitz1,2, T. Jenkins1,4, J. Dahlgren1,5,
C.E. Flodmark1,6, C. Marcus1,7, T.H. Inge1,4
1
Adolescent Bariatric Collaborative, ABC, International, Sweden
2
Gothenburg University- Institute of Clinical Sciences,
Department of Gastrosurgical Research, Gothenburg, Sweden
3
The Royal College of Surgeons of England, Department of Research, London,
United Kingdom
4
Cincinnati Children’s Hospital, Department of Surgery, Cincinnati, USA
5
Gothenburg University- Institute of Clinical Sciences, Department of Pediatrics,
Gothenburg, Sweden
6
Skåne University Hospital, Childhood Obesity Unit, Malmö, Sweden
7
Karolinska Institute, Department of Clinical Science-
Intervention and Technology CLINTEC, Stockholm, Sweden

Introduction
Adolescent prediabetes and type two diabetes mellitus (T2DM) are associated with
childhood obesity and are increasing in prevalence. Treatment is more challenging
than in adults. The Adolescent Morbidly Obese Subjects (AMOS) and Follow-up of
Adolescent Bariatric Surgery-5+ (FABS-5+) studies prospectively examined
adolescents (≤ age 21) following laparoscopic roux-en-Y gastric bypass (RYGB) for
severe obesity. This study reports the prevalence of prediabetes and T2DM in this
pooled cohort at baseline and one year after surgery.

Methods
One hundred and twenty-two adolescents (mean 16.8 years, 42 males) underwent
RYGB in either of two centralised units in Gothenburg, Sweden and Cincinnati,
USA. Patient selection criteria were BMI >40 or >35kg/m2 with co-morbidities.
Baseline diabetes status was assessed using American Diabetes Association
(ADA) criteria.

Results
Median BMI was 47.8kg/m2 at baseline and 31.8kg/m2 at one year. Prediabetes
and T2DM were observed in 43.4% (53/122) and 6.6% (8/122) at baseline and
13.9% and 1.6% at one year, respectively. Of those with prediabetes at baseline,
resolution was seen in 77.3% (41/53) at one year. Complete remission of T2DM
occurred in six of eight, and partial remission in the remaining two. Five incident
cases of prediabetes were detected at one year, while no incident cases of T2DM
were observed.

Table: Baseline BMI and diabetic status and change at one-year follow-up
(median values; Mann-Whitney-U test).
Conclusion
Prediabetes or T2DM was [IT1] observed in 50% of this international adolescent
bariatric cohort. Surgery improved or normalized glycemic control in most
prediabetics and diabetics in this group.
WCIDT-0010
Impact of bariatric/metabolic surgery on glycemic control

DIABETES SURGERY ABCD SCORE IS BETTER THAN DIAREM SCORE FOR


PREDICTING T2DM REMISSION AFTER METABOLIC SURGERY
W.J. Lee, Z. James, A. Abdullah, C. Shu-Chu, T. Jun-Juin, C. Jung-Chien, S. Kong-
Han
Min-Sheng General Hospital, Surgery, Taoyuan, Taiwan

Background: Metabolic surgery has been adopted as a novel treatment modality of


type 2 diabetes mellitus (T2DM) in obese patients. Scoring system might be helpful
in the selection of appropriate T2DM patients for metabolic surgery. This study
compares two grading systems with regard to the remission of T2DM after metabolic
surgery.

Methods: Outcomes of 345 (201 women and 144 male) patients who underwent
metabolic surgery for the treatment of T2DM with one year follow-up were assessed.
The DiaRem score is composed of age, HbA1c, medication and insulin usage. The
ABCD score is composed of the age, BMI, C-peptide levels and duration of T2DM
(years). The remission of T2DM after gastric bypass surgery was evaluated using
both scoring system.

Results: At one year after surgery, the weight loss was 26.5% and the mean BMI
decreased from 37.0 to 27.1 Kg/m2. The mean HbA1c decreased from 8.6 to 6.2%.
180(53.0%) patients had complete remission (HbA1c < 6.0%), 59(17.1%) patients
had partial remission (HbA1c < 6.5%) and 37(7.1%) patients improved (HbA1c <
7%). Both groups can predict the success of metabolic surgery but ABCD score has
a better differentiating prediction at patients of relative poor socre and who received
sleeve gastrectomy surgery.

Conclusions: Both DiaRem and ABCD score grading system can predict the
success of T2DM remission after metabolic surgery but ABCD score has a better
differentiating power.
WCIDT-0012
Impact of bariatric/metabolic surgery on glycemic control

GLYCEMIC CONTROL IN ZUCKER DIABETIC FATTY RATS AFTER BARIATRIC


SURGERY OR CALORIC RESTRICTION INDUCED WEIGHT LOSS
T. Lutz
University of Zurich, Zurich, Switzerland

Bariatric surgery models, in particular rodents with Roux-en-Y gastric bypass (RYGB)
and vertical sleeve gastrectomy (SG), are frequently used to study the beneficial
effects of weight loss surgery. Here, we monitored parameters of glucose metabolism
including the extent and duration of improved glycemic control after RYGB or SG in
Zucker Diabetic Fatty [ZDF] rats, a rat model of type 2 diabetes (T2DM); this was
compared with food restriction induced weight loss and rats receiving glucose
controlling medical therapy. Male ZDF rats underwent RYGB or SG surgery at 18
weeks of age and received postsurgical insulin treatment to maintain mid light phase
glycemia at 10-15 mmol/L. Sham operated rats were fed ad libitum feeding, or were
weight or glycemia matched to RYGB; the latter group received a combination of
insulin, metformin and liraglutide.RYGB and VSG rats required less daily insulin to
maintain mid light phase blood glucose levels below 15 mmol/L than controls (p <
0.001). Severe hypoglycemia occurred in several rats after RYGB; this was also
observed in a separate group of RYGB rats whose glycemia was monitored
continuously by telemetry. RYGB and SG significantly improved glycemic control in a
rodent model of advanced T2DM. Whilst short-term outcomes were similar, long-term
efficacy appeared marginally better after RYGB although this was tempered by the
increased risk of hypoglycemia.
WCIDT-0014
Impact of bariatric/metabolic surgery on glycemic control

PREDICT GLYCEMIC CONTROL AFTER METABOLIC SURGERY USING


MODIFIED HOMEOSTASIS MODEL ASSESSMENT (HOMA) AND 6-MINUTES
GLUCAGON STIMULATION TEST IN CHINESE OBESE TYPE 2 DIABETES
PATIENTS
S. Wong1, S. Liu1, A. Kong2, C. Lam3, E. Ng3
1
Prince of Wales Hospital, Department of Surgery, Hong Kong, Hong Kong- China
2
Faculty of Medicine- The Chinese University of Hong Kong,
Department of Medicine & Therapeutics, Hong Kong, Hong Kong- China
3
Faculty of Medicine- The Chinese University of Hong Kong, Department of Surgery,
Hong Kong, Hong Kong- China

Background: This study aims to evaluate the use of modified HOMA-B% and 6-
minute glucagon stimulation test to predict optimal glycemic control 6 months after
metabolic surgery in obese type 2 diabetes (T2DM) Chinese patients.

Methods: A consecutive cohort of T2DM patients (BMI>30kg/m2) who underwent


laparoscopic gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG) or
laparoscopic Roux-Y gastric bypass (LRYGB) were included for analysis. Beta-cell
function were assessed by modified HOMA-%BCP model using paired fasting glucose
and C-peptide (CP) assay 1 week before and 6 months after surgery. Pancreatic
beta-cell secretory function was further assessed by the change of CP level (DFCP =
Stimulated CP – Fasting CP) 6-minutes after 1mg intravenous glucagon stimulation.
Optimal glycemic control is defined as HbA1c<6.5% six months after operation.

Results: Fifty-four T2DM patients with mean age of 42.2±11.2 years, mean body
weight (BW) of 103.8±19.3kg and mean BMI of 38.6±5.8kg/m 2 underwent metabolic
surgery. These included 6 LAGB (11.1%), 38 LSG (70.4%) and 10 LRYGB (18.5%).
At 6 months, the BW were significantly reduced (-20.6±8.1kg, p<0.01)) while the
HbA1c level is significantly reduced from 8.4±1.7% to 6.3±1.2% while 42 patients
(79.6%) have achieved optimal control (p<0.01). Univariate analysis showed patients
with optimal glycemic control significantly higher HOMA-%BCP, fasting CP, Stimulated
CP, and DFCP level. The stepwise multivariate logistic regression analysis showed
that stimulated CP is the only factor significantly predicts glycemic control after
surgery (p=0.011, 95% CI 1.12-2.39).

Conclusions: Our current model suggested that stimulated C-peptide level predict
satisfactory glycemic control after metabolic surgery for T2DM patients.
WCIDT-0019
Impact of bariatric/metabolic surgery on glycemic control

THE EFFECT OF INTRA-GASTRIC BALLOON AND GLP-1 RECEPTOR AGONIST


THERAPY ON GLUCOSE METABOLISM AND WEIGHT LOSS ACCORDING TO
EATING BEHAVIOUR
E. Melinikova, E. Kravchuk, A. Neimark, A. Babenko
North West Medical Research Centre, Endocrinology, Saint Petersburg, Russia

Introduction: The aim of the study is to evaluate the contribution of different eating
styles in compensation of carbohydrate metabolism and weight loss in obese patients
with type 2 diabetes mellitus (T2DM) receiving therapy with glucagon-like peptide-1
receptor agonist (aGLP-1) or intra-gastric balloon (IGB).

Methods: 16 patients with T2DM and BMI ≥35 kg / m2 were divided into two groups:
9 patients received aGLP-1, 7 patients had IGB procedure. In all patients
anthropometric data were measured, Dutch Eating Behaviour Questionnaire (DEBQ)
was assessed, HbA1c was evaluated.

Results: All study participants had eating deviations, including 6 patients with
restrained type, 10 with mixed type.

After 6 months of treatment BMI reduction in patients treated with aGLP-1 was 5,2 ±
3,3%, and in group of IGB - 8,9 ± 4,2% (p = 0.05) and reduction in HbA1c 2,1 ± 0,6%
and 0,7 ± 0,3%, respectively (p = 0.05).

The data obtained in different groups are presented in the table.

Overeating type Restrained Mixed


Therapy type aGLP-1 IGB aGLP-1 IGB
Number of participants 3 3 6 4
BMI, kg / m2 51,8±3,0 кг/м2 57,5±15,7 46,4±6,2 44,3±5,3
HbA1c, % 8,6±2,7% 7,8±0,3 8,7±0,1% 8,0±0,5%
6 months therapy
BMI reduction, kg / m2 8,2±5,5% 10,2±6,5 6,7±0,5% 9,2±4,1
HbA1c reduction, % 2,1±0,7% 1,0±0,8 1,4 ±0,4% 1,3±0,2
Conclusion: In general IGB is more efficient in reducing body weight and aGLP-1
therapy leads to a better glycemic control. Patients with restrained eating type tended
to greater weight loss, but differences did not reach statistical significance.
WCIDT-0020
Impact of bariatric/metabolic surgery on glycemic control

EARLY RESULTS OF A RANDOMIZED CONTROL TRIAL OF TYPE 2 DIABETES


WITH BMI 27-32 FOR RYGB VERSUS BEST MEDICAL THERAPY
C.H. Tan, A. Cheng
Khoo Teck Puat Hospital, General Surgery, Singapore, Singapore

The benefical effect of bariatric surgery in improvement or resolution of type 2


diabetes (T2DM) in the morbidly obese is well documented, however evidence for the
not so obese is not so robust. We embarked on a RCT for the not so obese
population in Asia with BMI 27-32 comparing RYGB versus best medical therapy in
T2DM patient.

Suitable subjects aged 21-65, BMI 27-32, HbA1C >8%, T2DM <10 years and at least
1 co-morbidities on treatment, including hypertension, hyperlipidemia, micro/macro-
albuminuria or class 1 nephropathy, and retinopathy. They are on maximum
treatment from their primary care physicians or endocrinologist. They need to be GAD
negative and have a fasting C peptide level of >300. Those deemed suitable will be
randomized to the 2 study arms. We aim to recruit 20 subjects to each arm of the
trial.

We have a total of 6 patients randomized. 2 in the RYGB arm and 4 in the best
medical therapy arm. HbA1c levels fell 26-41.7% for the surgical arm compared to
6.8-32.6% for the best medical therapy arm. Mean percentage improvement in HbA1c
levels was 18.0% (surgery) versus 34.3% (best medical therapy), p<0.05. Fasting
plasma glucose levels fell 40.2-50.3% for the surgical arm compared to 10.4-25.3%
for the best medical therapy arm. Mean percentage improvement for fasting glucose
was 46.1% versus 16.8%, p<0.05. Waist circumference and excess weight loss
showed not statistical difference.

These are very early results in this RCT that suggest RYGB is better than best
medical therapy for treatment of T2DM with BMI 27-32
WCIDT-0025
Impact of bariatric/metabolic surgery on glycemic control

ASSESSMENT OF DIABETES REMISSION 5 YEARS AFTER BARIATRIC


SURGERY USING THE AMERICAN DIABETES ASSOCIATION (ADA) AND
INTERNATIONAL DIABETES FEDERATION (IDF) CRITERIA
S. Ravindra1, A. Humphreys1, A. Miras1, S. Allen1, A. Ahmed1, K. Moorthy1,
S. Purkayastha1, J. Cousins1, T. Tan1, H. Chahal1
1
Imperial College NHS Healthcare Trust, Imperial Weight Centre, London,
United Kingdom

Background: Bariatric surgery has impressive effects on the metabolic profile of


patients with type 2 diabetes (T2DM). However, the long-term remission rates of
T2DM based on the standardised criteria provided by the American Diabetes
Association (ADA) and International Diabetes Federation (IDF) are unknown.

Objective: To assess the percentage of patients with T2DM achieving the ADA and
IDF criteria for T2DM remission 5 years after bariatric surgery.

Methods: Clinical data were collected prospectively and analysed retrospectively for
82 patients with T2DM who underwent bariatric surgery (Roux-en-Y gastric bypass,
n=59; gastric banding, n=8; vertical sleeve gastrectomy, n=15) at the Imperial Weight
Centre and were followed up for 5 years.

Results: There were significant reductions in glycated haemoglobin, lipid and blood
pressure levels, weight and number of glucose-lowering medications at 5 years
following bariatric surgery compared to baseline. At 5 years, 23% and 13% patients
achieved complete and partial remission of T2DM based on the ADA criteria
respectively; 5% and 10% patients achieved optimisation and improvement of the
metabolic state based on the IDF criteria respectively. There were no significant
differences in remission rates between the surgical groups.

Conclusions: Bariatric surgery induced a significant and sustained improvement of


cardio-metabolic risk factors in patients with T2DM; however a relatively low number
of patients achieved T2DM remission at 5 years. These results suggest that whilst
surgery is still effective in the long term, more intensive concurrent medical therapy
may be required to achieve optimal cardio-metabolic targets.
WCIDT-0034
Impact of bariatric/metabolic surgery on glycemic control

INHIBITORY EFFECT OF BLOOD PLASMA TRIGLICERYDES IN THE


TREATMENT OF TYPE 2 DIABETES WITH GASTRIC CONTRACTILITY
MODULATION (GCM)
J. Kozakowski1, H.E. Lebovitz2, A. Kiciak3, W. Zgliczyński4, W. Tarnowski5
1
Medical Centre of Postgraduate Education, Warsaw, Poland
2
State University of New York Health Science Center at Brooklyn, Medicine,
New York, USA
3
Medical Center of Postgraduate Education, General-
Oncological and Gastrointestinal Surgery, Warsaw, Poland
4
Medical Center of Postgraduate Education, Endocrinology, Warsaw, Poland
5
Medical Center of Postgraduate Education, General-
Oncological and Gastrointestinal Surgery, Warsaw, Poland

Background:
A retrospective data indicate that improvement in glycemic control in patients with
type 2 diabetes mellitus (T2DM) treated with GCM is inversely correlated with the
fasting plasma triglyceride (TG) levels. We present the result of prospective study.

Methods:
12 (9F 3M) DM2T overweight/obese patients that were implanted with Diamond
system (MetaCure Ltd), and completed a 12 month randomized crossover study were
enrolled into an additional 6 month study in which all had TG measurements and
received GCM stimulation.

Results:
In group with normal blood triglycerides (<1.7 mmol/l) statistically significant decrease
in HbA1c by 1.26% (8.32±0.7 to 7.06±0.4%), body weight by 3.6 kg (89.3±4.3 to
85.7±2.9 kg ) and waist circumference by 4.9 cm (113.1±1.8 to 106.2±5.3 cm) were
observed. In contrast, in patients with high blood triglycerides HbA1c was reduced
only by 0.3% and the change was not statistically significant. No significant effects
on body weight and waist circumference were observed in this group. No adverse
effects of Diamond therapy has been observed

Conclusions:
DIAMOND™ therapy is safe, well tolerated, and has significant impact on HbA1c and
weight loss in the patients with normal blood plasma TG. The treatment may probably
become an alternative to the use of incretins or insulin. Therapy provides good
glycemic control with minimal patient compliance and with an added benefit of body
weight loss, without incretins-related adverse effects.The data further evidence the
existence of a triglyceride sensitive glucose regulatory pathway in humans.
WCIDT-0041
Impact of bariatric/metabolic surgery on glycemic control

LAPAROSCOPIC SINGLE ANASTOMOSIS SLEEVE ILEAL BYPASS (SASI


BYPASS) : TECHNIQUE AND PRELIMINARY RESULTS
T. Mahdi
Al Qassimi Hospital, Bariatric and Metabolic center, Sharjah, United Arab Emirates

SASI bypass is a Novel Metabolic/Bariatric Surgery operation based on mini gastric


bypass operation and Santoro 's operation in which a sleeve gastrectomy is followed
by an side to side gastroileal anastmosis . We review the results obtained on the first
50 patients who underwent laparoscopic SASI bypass with one year follow up.
Sleeve gastrectomy was performed over a 36-Fr bougie, 6 cm from the pylorus, 200
cm from the iliocecal valve the ileum brought to be anastmosis side to side with the
antrum. 17 men and 33 women with mean BMI 47 Kg/m2 were operated on.
Hypertension was present in 25 %, sleep apnea in 10 % , hypertriglyceridemia in 70
% , Hypercholesterolemia in 50 % and all patients are type 2 diabetes , most of them
have antidiabetic therapy for at least 3 years . There are one complete stricture at
gastroileal anastmosis which is revised after 3 months. Follow up is complete in all
patients. EBWL reached 95.6% at one year. At one year mild anemia in one patient
and one patient has low albumin level but above 3, all patients have normal glucose
level in the first month after surgery with no need to antidiabetic therapy. SASI
bypass is a promising operation which offers excellent weight loss and metabolic
result. The elimination of two ways for passage of food and one anastmosis decrease
nutritional deficiency and the possibility of surgically related complications.
WCIDT-0042
Impact of bariatric/metabolic surgery on glycemic control

EFFICACY OF MINI GASTRIC BYPASS IN DIABETIC PATIENTS WITH BODY


MASS INDEX LESS THAN 34 KG/M2 , SHARJAH EXPERIENCE
T. Mahdi
Al Qassimi Hospital, Bariatric and metabolic center, Sharjah, United Arab Emirates

UAE has diabetes rate of roughly 20 percent for residents and 25 percent for Emirati
nationals. The aim of our study was to evaluate the efficacy and safety of MGB in
UAE subjects with type 2 diabetes mellitus. From March 2011 to March 2014,
patients with T2DM underwent MGB enrolled in this study. The change in fasting
blood sugar, postprandial blood sugar, and glycosylated hemoglobin, C-peptide, total
body weight and the use of oral hypoglycemic agents and insulin at the end of one
year were studied. A total of 135 patients with type 2 diabetes mellitus (65 women
and 70 men age 40.5 ± 7.9 years, body mass index 29.91 ± 2.43 kg/m2, and
hemoglobin A1c 8.9% ±1.6%) had undergone MGB. Before MGB, 110 patients
(81.5%) required oral hypoglycemic agents and 25 patients (18.5%) required oral
hypoglycemic agents and insulin). Resolution of type 2 diabetes was achieved in 108
(80%), remission in 25 (18.5%) and failure in 2 (1.5%) patients at one year after
MGB. The diabetes resolution rates for those with pre-operative C-peptide <3, 3--6,
and >6 ng/mL were 3 /25 (12%) , 85/90 ( 94.4%) and 20/20 (100%), respectively
.MGB is an effective the treatment of T2DM in with Body mass index less than 34
Kg/M2 UAE patients. C-peptide as the predictor of successful T2DM resolution
should be evaluated and used as patient selection criteria. Pending long-term
evaluation, MGB is an effective, relatively low-risk, and low-failure diabetic surgery
procedures .
WCIDT-0046
Impact of bariatric/metabolic surgery on glycemic control

EFFECT OF WEIGHT REGAIN ON GLYCAEMIC CONTROL IN TYPE 2 DIABETIC


PATIENTS SUBMITTED TO BILIOPANCREATIC DIVERSION WITH BMI BELOW
35
F.S. Papadia, G.B. Camerini, F. Carlini, N. Scopinaro
IRCCS-AOU San Martino-Istituto Nazionale per la Ricerca sul Cancro,
Department of Surgical Sciences and Integrated Diagnostics DISC, Genoa, Italy

Background/ aims:

To investigate the effect of weight regain (WR) on glycaemic control in diabetic


(T2DM) patients with BMI< 35 after biliopancreatic diversion (BPD).

Summary:

All bariatric operations are beneficial for T2DM patients due to the weight loss they
cause. Diversionary operations are thought to have a benefit independently of weight
loss. If so, WR should not be associated with worsening of glucose homeostasis. To
test this hypothesis, we analyzed glucose homeostasis and WR in T2DM patients
submitted to BPD with BMI< 35.

Materials and methods:

Retrospective analysis of data of T2DM patients with BMI< 35 submitted to BPD who
regained weight up to 90% of the preoperative weight.

Mean body weight (BW), BMI, fasting serum glucose (FSG) and HbA1c
preoperatively, at the peak of the weight loss (nadir), and at the maximum
postoperative weight (zenith) were investigated.

Results:

96 T2DM patients with BMI< 35 were submitted to BPD from 2007 to 2013
((NCT00996294, NCT01046994, NCT01041768). Out of those, 19 patients lost <
10% of the initial weight.

Values of BW, BMI, FSG and HbA1c preoperatively, at nadir and at zenith.

Preoperatively Nadir Zenith


BW (kg) 83.3 72.9 79.4
BMI (kg/m2) 29 25.4 27.0
FSG (mg/dl) 234 130.0 139.5
HbA1c % 9.7 6.4 6.7

p= n.s. nadir vs. zenith for FSG and HbA1c

p< 0.05 nadir vs. zenith for BW and BMI

Conclusions:

WR is not associated with significant deterioration of T2DM after BPD. The


improvement of T2DM after BPD does not seem to be related only to weight loss.
WCIDT-0059
Impact of bariatric/metabolic surgery on glycemic control

EARLY EFFECTS OF RYGB AND BPD ON INSULIN SENSITIVITY AND


SECRETION AND ON INCRETIN
L. Castagneto-gissey1, J. Casella Mariolo1, G. Mingrone2, A. iaconelli2, C. guidone2,
E. capristo2
1
King's College Hospital, General Surgery, London, United Kingdom
2
Catholic University of Rome, Internal Medicine, Rome, Italy

Objective: To compare the effect of Bilio-Pancreatic Diversion (BPD) with Roux-en-Y


Gastric-Bypass (RYGB) on insulin sensitivity, on its secretion and on incretin
response to an oral-glucose tolerance-test (OGTT).

Research Design and Methods: Sixteen morbidly-obese subjects undergone RYGB


(n=7) or BPD (n=9) were studied. Insulin sensitivity (by OGIS and QUICKI) and
secretion (ISR by C-peptide deconvolution) were assessed before and 1 month after
surgery. Incretin (gastric-inhibitory peptide, GIP and glucagon-like peptide-1, GLP-1)
levels after OGTT were measured.

Results: The glucose clearance by OGIS improved significantly after both RYGB and
BPD (30.72±16.09 vs. 45.64±11.81%). However, the ratio glucose/insulin area-under-
the-curve (19.01±34.46 vs. 408.15±72.15%) and the hepatic insulin resistance by
QUICKI (4.84±3.49 vs. 43.20±13.38%) increased more (P<0.01) after BPD than after
RYGB. Basal-ISR was increased after RYGB (34.68±7.32%) and reduced after BPD
(-23.92±9.84% P<0.01). Total-ISR was not significantly changed after RYGB
(54.35±79.62%) while it was reduced of 1/3 after BPD (-34.63±9.93%, P<0.01).

GLP-1 incremental-area-under-the-curve (pmol·ml-1·min) raised from 3104.14±634.65


to 6176.00±433.99 (P<0.0001) after RYGB and from 2466.75±155.11 to
3540.67±359.70 (P<0.05) after BPD. In contrast, GIP-AUC decreased from
7545.00±644.93 to 5276.67±717.70 pg·ml-1·min (P<0.01) after BPD, but remained
unchanged after RYGB.

The GLP-1 and GIP time courses are depicted below.


Conclusions: Although RYGB and BPD equally improve insulin sensitivity, the effect
is more pronounced after BPD in particular regarding hepatic insulin resistance. Their
inverse effect on insulin secretion might be related to a differential effect on incretin
production. In fact, glucose-induced GLP-1 release is of greater magnitude after
RYGB whereas a net reduction of the GIP release is observed after BPD.
WCIDT-0062
Impact of bariatric/metabolic surgery on glycemic control

ALTERATIONS IN THE PROLIFERATION OF PANCREATIC CELLS IN PATIENTS


WITH SEVERE HYPOGLYCEMIA FOLLOWING ROUX-EN-Y GASTRIC BYPASS

M. Patti1, A. Goldfine1, J. Hu1, D. Hoem2, A. Molven3, J. Goldsmith4,


W. Schwesinger5, F. Folli6, R. Kulkarni1
1
Joslin Diabetes Center, Research Division, Boston, USA
2
Haukeland University Hospital, Department of Surgery, Bergen, Norway
3
University of Bergen, Jebsen Center for Diabetes Research, Bergen, Norway
4
Beth Israel Deaconess Medical Center, Department of Pathology, Boston, USA
5
University of Texas Health Science Center at San Antonio, Department of Surgery,
San Antonio, USA
6
University of Texas Health Science Center at San Antonio, Department of Medicine,
San Antonio, USA

Severe hypoglycemia with neuroglycopenia is recognized as a rare, but debilitating


complication of Roux-en-Y gastric bypass (RYGB) surgery. Hypoglycemia in this
syndrome is typically postprandial, and increased concentrations of plasma insulin
and incretin hormones, including glucagon-like-peptide-1 (GLP1), are implicated in its
pathogenesis. Histopathologic examination of pancreas samples from patients with
this syndrome who underwent pancreatectomy due to refractory hypoglycemia has
demonstrated increased islet mass and/or nuclear diameter. To determine whether β-
cell proliferation or apoptosis are altered in patients with post-RYGB hypoglycemia,
we compared pancreatic tissue from 11 severely affected patients to 6 samples from
normoglycemic patients undergoing pancreatic surgery for benign lesions (controls)
and to 7 samples from patients with hypoglycemia due to insulinoma. We find a 4.5-
fold increase in proliferative cell nuclear antigen (PCNA) in insulin-positive cells from
patients with post-RYGB hypoglycemia (36.5+4.1 vs. 8.1+1.8, p<0.0001), suggesting
active and ongoing β-cell proliferation in this syndrome. Markers of apoptosis,
including p21 and p27, did not differ. By contrast, markers of both proliferation and
apoptosis were increased in insulinoma tissue compared to adjacent normal islets or
controls. We conclude that islet cell replication is increased in patients with post-
RYGB hypoglycemia, and may contribute to increased β-cell mass and the distinct
metabolic profile in these patients.
WCIDT-0064
Impact of bariatric/metabolic surgery on glycemic control

REMISSION OF TYPE-2 DIABETES IN OBESE PATIENTS: COMPARISON OF


SLEEVE GASTRECTOMY WITH GASTRIC BYPASS/MINI-BYPASS
M.A. Motamedi1, A. Khalaj2, M. Barzin3
1
Research Institute for Endocrine Sciences, Obesity Research Center, Tehran, Iran
2
Shaahed University, Department of Surgery, Tehran, Iran
3
Research Institute for Endocrine Sciences, Obesity Research Center, Tehan, Iran

Background: Metabolic surgery has been proposed for the treatment of type 2
diabetes mellitus (T2DM). This study aims to compare two different surgical
techniques for the treatment of T2DM.

Methods: Patients presenting to a tertiary care clinic aging 20 to 70 years with T2DM
and BMI ≥ 30 kg/m2 were assigned to either laparoscopic sleeve gastrectomy (group
A) or laparoscopic gastric bypass/mini-bypass (group B) based on an individualized
treatment plan.

Results: Of the 78 patients, 53 (68%) were in group A and 25 (32%) in group B.


Gender (87% female), mean age (44.3 ± 11) years), HbA1c level (7 ± 1.5%), and
duration of T2DM (5 ± 4.6 years) did not differ significantly between the two groups.
9.8% and 32% of patients were under insulin therapy in groups A and B, respectively.

The 6-month follow up data show that the mean BMI decreased from 43.7 ± 5.8 to
32.3 ± 4.2 kg/m2 and the excess weight loss was 60.5 ± 15.1% in group A and 66.7 ±
23.2% in group B. HbA1c decreased to 5.9 ±1.1%. Remission of T2DM (defined as
fasting plasma glucose <110 mg/dl and HbA1c <6.5%) occurred in 36 (76.5%) of the
patients (80% in group A versus 66.7% in group B). Furthermore, T2DM duration and
type of surgery were not predictors of diabetes remission after metabolic surgery.

Conclusion: Both techniques show satisfactory results for the control and treatment
of T2DM. Future longer-term outcomes in larger patient groups will provide more
insight in this regard.
WCIDT-0069
Impact of bariatric/metabolic surgery on glycemic control

METABOLIC PATHWAYS FROM BARIATRIC SURGERY TO TYPE 2 DIABETES


MELLITUS
J. Graessler1, V. Kamvissi1, K.M. Schulte2, F. Rubino2, S.R. Bornstein1
1
University Hospital Dresden, Internal Medicine III, Dresden, Germany
2
King’s College Hospital, Department of Surgery, London, United Kingdom

Bariatric surgery has helped patients attain not only significant and sustained weight-
loss, but has also proved to be an effective procedure of reversing various obesity-
related co-morbidities. The impressive rates of remission or resolution of type 2
diabetes mellitus (T2D) following bariatric surgery are well documented and have
rightly received great attention. Less understood are the effects of bariatric surgery
on metabolic pathways underlying diabetes alleviation. Thanks to the availability of
increasingly sensitive laboratory tools, the emerging science of Lipidomics and
Metagenomics is poised to offer significant contributions to our understanding of
metabolic pathways involved in the pathogenesis of T2D. They are set to identify
novel mechanisms explaining how the varied approaches of bariatric surgery produce
the remarkable improvements in multiple organs observed during patient follow-up.
This presentation reviews recent and novel findings in patients through the lens of
lipidomics with an emphasis on T2D.
WCIDT-0070
Impact of bariatric/metabolic surgery on glycemic control

LONG TERM CLINICAL AND FUNCTIONAL IMPACT OF BILIOPANCREATIC


DIVERSION ON TYPE 2 DIABETES IN NON MORBIDLY OBESE PATIENTS
G. Adami1, N. Scopinaro1
1
University of Genova, Surgery, Genova, Italy

Objective: To evaluate metabolic outcome of on non morbidly obese patients with


type 2 diabetes (T2DM) after biliopancreatic diversion (BPD).

Material and Methods: two groups of T2DM patients with different degree of obesity
(non morbidly obese, NMO, 17 cases, BMI 25-35/m2 and morbidly obese, MO, 13
cases, BMI > 35kg/m2 ) were studied prior to and at 1 and 5 year after BPD. Insulin
secretion was assessed by acute insulin response (AIR) to intravenous glucose load
and by glicogenetic index (IGI).

Results: In all MO patients T2DM was remitted or controlled (1 case) at 1 year and
results were maintained at 5 years; AIR (μU/ml) and IGI (μU/ml-mg/ml) improved at 1
year (from 0.1± 3.1 to 18.52 ± 21.9, and from 6.0 ± 8.5 to 9.1 ± 22.8, respectively)
with a further increase (to 24.8 ± 25.5 and to 14.3 ± 13.8, respectively) at 5 years.
Within the NMO group, T2DM was remitted in 1/17 and controlled in 14/17 patients at
1 year, and remitted and controlled at 5 years in 2/17 and 4 /17 patients,
respectively; AIR (μU/ml) and IGI (μU/ml-mg/ml) remained unchanged throughout
the postoperative period (from 0.31 ± 9.26 to 1.5 ± 2.8 at 1 and to 0.4 ± 3.29 at 5
year for AIR, and from 2.2 ± 4.9 to 1.3 ± 9.0 at 1 and to 2.3 ± 3.3 at 5 five year for
IGI).

Conclusions: Following BPD restoration of beta cell secretion/production plays a


pivotal role in determining the postoperative diabetic remission.
WCIDT-0072
Impact of bariatric/metabolic surgery on glycemic control

THE LONG-TERM IMPACT OF BILIOPANCREATIC DIVERSION ON GLYCEMIC


CONTROL IN THE SEVERELY OBESE WITH TYPE 2 DIABETES MELLITUS IN
RELATION TO PRE-OPERATIVE DURATION OF DIABETES
G. Adami, N. Scopinaro
University of Genova, Surgery, genova, Italy

Bariatric surgery has been shown to be effective in severely obese patients with type
2 diabetes mellitus (T2DM).: retrospective analysis investigates of two subsets of
severely obese patients who had undergone BPD from 1984 to 1995, the first
including 52 patients with a preoperative T2DM duration of ~ 1 year (SD group), 49
on oral agents and 3 on insulin, and the second comprehending the 68 patients who
had been diabetic for more than 5 years prior to BPD (LD group), 52 on oral agents
and 16 on insulin. Postoperatively T2DM was regarded as in remission when fasting
serum glucose (FSG) was lower than 100 mg/dl on free diet and without antidiabetic
therapy.: At 5-10 years after BPD, the FSG mean values reduced within normality
and the results were strictly maintained at more than 15 years. Compared with the LD
group, in the SD patients the mean FSG values and the number of individuals without
T2DM remission were lower both at 5-10 (84 vs. 93 mg/dl, p<0.01 and 0/31 vs. 8/54
subjects, p<0.04, respectively) and at more than 15 years (85 vs. 99, p<0.02 and
1/31 vs. 19/41 subjects, p<0.0012, respectively). Furthermore, after BPD the number
of subjects with dyslipidemia strongly reduced (p<0.001) in both groups, values at 5-
10 years remaining very similar to those observed at more than 15 years. These
results indicate that severely obese patients with longer T2DM duration have a less
good metabolic outcome maintained at long and very long term following BPD.
WCIDT-0077
Impact of bariatric/metabolic surgery on glycemic control

T2DM STATUS IN SLEEVE GASTRECTOMY PATIENTS AFTER WEIGHT


REGAIN: 2 YEARS FOLLOW UP OF 452 PATIENTS
D. Sargsyan1, M. Bashah1, M. Al Kuwari1, W. Elhag1, M. Rizwan1, M. Karam1,
A. Al Naggar1, N. Khidir1, I. Mustafa1, M. El Sherif1
1
Hamad General Hospital, Bariatric and Metabolic Surgery- HG-G-0515, Doha, Qatar

Introduction: Morbid obesity and T2DM are highly endemic in Gulf countries. Sleeve
gastrectomy (LSG) has become procedure of choice for treatment of morbid obesity
and T2DM.

Objectives: Excess weight loss (%EWL) following bariatric surgery, status of T2DM
in 452 diabetic patients, rate of T2DM relapse in relation to weight regain were
examined.

Methods: Data recorded: %EWL, use of diabetic medications, pre- and postop levels
of fasting blood glucose (FBG) and HbA1c.

Results: Out of 452 patients, 67% were females, mean age was 35 years, mean BMI
was 47 kg/m2. Follow up data obtained in 56% of the patients (mean f/u duration 20
months (SD14)) showed %EWL of 72% and mean delta-BMI was 16kg/m2 (SD 10).
Out 452 patients followed 61% stopped diabetic medications, 34% - reduced the
dose and number of medications, 2.4% remained unchanged and 1.6% relapsed.
Pre- and postop mean FBG was 10.8 and 5.9 mmol/l (p<0.01) and HbA1c was 8.4
and 6.2 accordingly (p<0.01). Among patients who completed 2 years follow up there
was a 14% weight regain. 54% of patients with weight regain were still off diabetic
medications with mean postoperative FBG and mean HbA1c of 5.8 and 6.1
accordingly. 37.5% of the patients still remained on reduced dose and number of
medications, and only 6.3% resumed all preop medications.

Conclusions: LSG is a powerful operation and have comparable results with bypass
in terms of weight loss and diabetes control. Patients with weight regain remained in
T2DM remission in 54% of cases at 2 years.
WCIDT-0084
Impact of bariatric/metabolic surgery on glycemic control

SODIUM DEPENDENT GLUCOSE INTESTINAL ABSORPTION PLAYS A


CRUCIAL ROLE IN POSTPRANDIAL GLUCOSE HOMEOSTASIS AFTER ROUX-
EN-Y GASTRIC BYPASS IN THE MINIPIG
G. Baud1, M. Daoudi1, H. Thomas1, V. Raverdy1, P. Pigny2, K. André1, V. Gmyr1,
R. Caiazzo1, F. Pattou1
1
Lille University Hospital, Endocrine and Metabolic surgery, Lille, France
2
Lille University Hospital, Biology Pathology Center, Lille, France

Objective: Anatomical changes of the intestinal limbs, induced after Roux-en-Y


Gastric bypass (RYGB), play a key role in glucose disposal, thereby improving
glycemic control. The aim was to explore the respective roles of the alimentary (AL),
the common (CL) and the biliary (BL) intestinal limbs of RYGB on postprandial
glucose homeostasis.

Methods: RYGB was performed on lean adult Göttingen minipigs (n = 30). To study
the $role of AL and CL on glucose uptake, insulin, and GLP-1 secretion, we
performed intestinal clamp tests during the progression of a mixed meal. To
investigate the effect of bile and sodium on carbohydrates uptake in the AL, glucose
and D-xylose were injected in the AL without or with Sodium-Glucose Linked
Transporter-1 (SGLT1) inhibitor phlorizin, before and after administration of fresh bile
or NaCl in the AL.

Results: We first demonstrated that carbohydrates absorption is abolished in the AL,


which occurred only in the CL (P<0.001) where it triggered insulin (P<0.001) and
GLP-1 secretion (P<0.001). Carbohydrates absorption in the AL was restored after
the addition of bile (P<0.001) and was blunted by phlorizin (P=0.61). Furthermore, we
demonstrated a decrease of sodium concentration in the AL (62±6mEq/L, P<0.01)
due to bile exclusion. Thus, the restoration of isotonic concentration of sodium in the
AL was sufficient to restore glucose absorption (P<0.001).

Conclusion: The present study uncovered a previously unsuspected effect of


gastrointestinal exclusion on sodium dependent glucose intestinal transport, and its
pivotal role in the changes of postprandial glucose homeostasis after RYGB.
WCIDT-0085
Impact of bariatric/metabolic surgery on glycemic control

BETA-CELL FUNCTION AND MASS AFTER GASTRIC BANDING, ROUX-EN-Y


GASTRIC BYPASS AND VERTICAL SLEEVE GASTRECTOMY: A PROSPECTIVE
CONTROLLED STUDY
G. Baud, V. Raverdy, M. Pigeyre, R. Caiazzo, F. Pattou
Lille University Hospital, Endocrine and Metabolic surgery, Lille, France

Objective: The effect of bariatric surgery on pancreatic β-cell remains unclear. The
aim of this study was to investigate the effect of adjustable gastric banding (AGB),
Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on β-cell
mass and function.

Methods: We enrolled in a prospective study 555 obese subjects (41.1±11.4 years,


48.3±7.9 kg.m2, 76% Female) with normal glucose tolerance (n=129), impaired
glucose tolerance (n=239), or T2D (n=187). An oral glucose tolerance test was
performed prior to and one year after AGB (n=128), RYGB (n=363) or VSG (n=64).
Glucose, insulin, and C-peptide levels were measured at 0, 30 and 120 mn for
calculating validated indices of insulin resistance, β-cell function, β-cell glucose
sensitivity, and β-cell mass.

Results: Insulin resistance, β-cell mass and function were similar prior to AGB,
RYGB and VSG (P=0.4 to 0.9; one way ANOVA). At one year, insulin resistance
(Matsuda index) decreased in association with weight loss (P<0.001; multivariate
linear regression), independently of the type of surgery (P=0.165). β-cell function
(insulinogenic index) and glucose sensitivity (oral disposition index) increased in
inverse correlation with insulin resistance (P<0.001), independently of the type of
surgery (P=0.610). Functional beta cell mass (fasting C-peptide/glucose) decreased
in association with weight loss, triglyceride levels and insulin sensitivity (P<0.05)
independently of the type of surgery (P=0.103). All results were confirmed when
analyzed only in T2D.

Conclusion: Bariatric surgery decreased functional β-cell mass but improved β-cell
function and β-cell glucose sensitivity in association with insulin sensitivity,
independently of the type of procedure.
WCIDT-0090
Impact of bariatric/metabolic surgery on glycemic control

DUODENOJEJUNAL BYPASS SLEEVE (ENDOBARRIER) TRANSIENTLY


IMPROVES DIABETIC CONTROL WHILST IN SITU - 'THERE IS NO HANGOVER
EFFECT'
H. Younus, S. Chakravartty, A. Patel
Kings College Hospital, Minimal access Surgery, London, United Kingdom

Background:
Endoscopically placed duodenal-jejunal bypass sleeve (EndoBarrier) is a removable
device that, in addition to its clinically proven effectiveness for weight control in obese
patients, improves type II diabetes soon after insertion. The device has to be
removed at 12 months. It has been suggested that improvement of diabetes control
persists after removal of the device, “the hangover effect”. Theaimof this study was to
observe the effect of the endobarrier on diabetes control whilst in situ and after
explantation.

Methods:
A cohort of 12 morbidly obese patients with type II diabetes and an EndoBarrier
inserted for 1 year, were observed during and after explantation. Outcome measures
included, excess weight loss (%EWL), HbA1c (%), fasting blood glucose levels (FBG-
mmol/L) and anti diabetic medication; at 3, 6, 9,12 months and 3 months post
removal. Data is represented as mean ± standard error of mean.

Results:
The patients had a mean age of 55±2 (years), body mass index 49±3 (kg/m2). Onset
of diabetes diagnosis was 6±1.8 years. Following insertion of the Endobarrier HbA1c
improved from the preoperative level of 8.5±0.4 to 7.1±0.4 at 3 months, to a maximal
effect at 9 months of 6.9±0.4, p<0.05. Three months after removal of the EndoBarrier
HbAIc had returned to preoperative values 9.1±0.7, p=ns. EWL at 9 months post
insertion of EndoBarrier was 20±4 and at 3 months post removal was 17.7±5.

Conclusion:
EndoBarrier results in transient improvement of diabetes control whilst in situ. On
explantation of the device the improvement in diabetes control is not maintained.
WCIDT-0095
Impact of bariatric/metabolic surgery on glycemic control

SELECTION OF BYPASS VS SLEEVE FOR THE MANAGEMENT OF TYPE-2


DIABETES: IS THERE CLEARLY A DIFFERENCE?
A. G. Bhasker1, J. Dixon2, M. Lakdawala1
1
Center for Obesity and Digestive Surgery, Bariatric Surgery, Mumbai, India
2
Baker IDI Heart and Diabetes Institute- Melbourne, Head Clinical Obesity Research,
Melbourne, Australia

On the basis of knowledge of predictors of diabetes remission, patients were


counselled prior to surgery, and those at lower risk of remission tend to choose Roux-
en-Y gastric bypass (RYGB) rather than sleeve gastrectomy (SG). How did these
patients go?

Methods: 186 consecutive patients of Indian ethnicity (M:F 89:97) with type 2
diabetes and HbA1c > 6.5 were assessed before and 1year following surgery. Age,
BMI, C-peptide and duration of diabetes (ABCD - described by WJ Lee), baseline
HbA1c and % weight loss were tested as modifiers. We present remission rates
(HbA1c ≤ 6.0%), and between group remission odds ratio (OR) and adjusted OR after
controlling for key modifiers.

Results: Patients selecting RYGB (n=89) vs SG (n=97) were older (56 vs 44.2
years), had a lower BMI (44.1 v 46.6 kg/m2), lower C-peptide (3.5 v 4.7 ng/ml),
greater duration of diabetes (8 vs 3 years) and higher HbA1c (9.0% and 7.8%)
respectively p<0.05 for all (combined R2=0.38). Weight loss at 1year was 27% and
30% for RYGB and SG respectively (p=0.01). Remission at 1 year was achieved by
37% of patient selecting RYGB and 74% for the SG (OR = 0.21, 95% CI 0.11-0.41,
p<0.001). After adjusting for ABCD the adjusted OR (AOR) still favoured the SG
(AOR = 0.32, 0.14-0.74, p=0.01), and adjustment for HbA1c and weight loss (AOR
0.4, 0.17-0.95, p=0.038) attenuated the effect.

Conclusion: The analysis suggests SG may be superior to RYGB in this Indian


population. A randomized controlled trial is needed to clarify the relative benefit.
WCIDT-0101
Impact of bariatric/metabolic surgery on glycemic control

MEDIUM-TERM EFFECT OF GASTRIC BYPASS ON INSULIN AND GLUCOSE


RESPONSE IN A WEIGHT STABLE MINIPIG MODEL
L. Hurtado
Minimally invasive Surgery Centre Jesús Usón, Laparoscopy Unit, Cáceres, Spain

Introduction:

Gastric bypass surgery (GBP) in obese patients can dramatically improve the glucose
homeostasis, regardless of weight loss. It has been hypothesized (foregut theory)
that this procedure may reduce the signals arise from de proximal intestine and which
negatively affect insulin sensitivity. The objective of this study is to study how gastric
bypass plays a role in glucose metabolism in the obese subject, regardless of weight
loss.

Methods:

Adult Göttingen obese minipigs (n=9, 52.5 kg) underwent a gastric bypass (30 cc
gastric pouch/100 cm alimentary limb). All animals were subjected to a repeated
metabolic evaluation at baseline (T1), and 4 months after surgery (T2). At each time
point, serum insulin (ELISA Kit), glucose levels (oral tolerance test) and GLP-1 were
measured. Other parameters of interest (weight and body circumferences) were
taken in account in order to assure the same body condition.

Results:

Body weight remained unchanged four month after surgery (datos). Plasma glucose,
insulin and GLP-1 levels in T1 were above reference values. After gastric bypass,
fasting glucose and insulin were dramatically modified, both parameters showed a
statistically significant reduction compared to baseline values (p=0.001). In particular,
the minipigs were glucose normalized to (T1:102.22 vs. T2:83.88). Conversely,
fasting GLP-1 were not modified significantly by GBP.

Conclusion

GBP induced a dramatic increase of insulin and glucose responses in obese


minipigs. Our results support the use of GBP for treating diabetes in patients with a
BMI under 35 kg/m2. Further preclinical studies help to clarify the metabolic effects of
GBP.
WCIDT-0105
Impact of bariatric/metabolic surgery on glycemic control

SHORT AND MID TERM METABOLIC EFFECTS OF ROUX-Y-GASTRIC BYPASS


AND SLEEVE GASTRECTOMY IN MORBIDLY OBESE SUBJECTS WITH TYPE 2
DIABETES
L. Genser1, G. Baud2, M. Pigeyre3, H. Verkindt1, R. Caiazzo2, F. Pattou2
1
Lille University Hospital, General and Endocrine surgery, Lille, France
2
Lille University Hospital- Inserm U 859, General and Endocrine surgery, Lille, France
3
Lille University Hospital- Inserm U 859, Nutrition, 59037, France

Background: Laparoscopic-Roux-Y-gastric-bypass (LRYGB) and Sleeve-


gastrectomy (LSG) are common bariatric procedures known to markedly ameliorate
Type-2-Diabetes-Melitus (T2M) in morbidly obese patients, often resulting in disease
remission even before weight loss occurs. To date, it is unclear which of these
procedures allow the best metabolic results

Objective: Compare the short and midterm results of LRYGB and LSG concerning
metabolic control and weight loss in T2M morbidly obese patients.

Methods: Outcomes of 284 morbidly obese patients with T2DM who underwent
primary LRYGB or LSG with 2-year follow-up were assessed. This was a
retrospective review of prospectively collected data. The primary endpoint was the
proportion of patient with complete remission defined as glycated hemoglobin
(HbA1C)< 6% and fasting blood glucose (FBG)<5.6 mmol/L off diabetic medications

Results: 95% (n=269) completed 24-months of follow-up.At 2 year the proportion of


patients achieving the primary endpoint was 45 %(n=108/239) in LRYGB group
versus 26%(n=8/30) in the LSG group(P=0.03). Glycemic control improved in both
group, with a HbA1C level of 6.01±0.07% in LRYGB group versus 6.54±0.2% after
LSG (P=0.01) with fewer antidiabetic (p=0.05) and lipid medications (p=0.04) after
LRYGB. Weight loss was greater after LRYGB than after LSG (28.9±10.4kg
vs24.7±9.7kg P=0.03). The 10-year-cardiovascular risk score improved significantly
more after LRYGB both in men(p<0.0001) and women(p<0.0001). 25 patients(9.3%)
underwent reoperation with no difference between procedures (P=0.7). There were
no deaths or life-threatening complications

Conclusions: In morbidly obese patients with T2DM, both procedures are effective
at improving glycemic control at 2 years, but LRYGB was more likely to achieve
complete remission
WCIDT-0108
Impact of bariatric/metabolic surgery on glycemic control

LONG-TEMRN RESULTS OF LAPAROSCOPIC SLEEVE GASTRECTOMY WITH


DUODENOJEJUNAL BYPASS FOR TYPE 2 DIABETES MELLITUS
Y. Seki, K. Kasama, H. HIdenori, A. Watanabe
Yotsuya Medical Cube, Weight Loss and Metabolic Surgery Center, Chiyoda-ku,
Japan

Background:

LSG-DJB which has been positioned as a novel bariatric procedure is the


combination of vertical sleeve gastrectomy and proximal intestinal bypass and is
theoretically expected to have strong anti-diabetic effect. However, long-term results
are unknown.

Methods:

In this analysis, consecutive 120 patients (F/M=61/59, mean age 44.8±7.9 years) with
T2DM who underwent LSG-DJB and were followed up over 1 year were included.
The mean weight and BMI were 105.7±21.5 kg and 38.5±7.3 kg/m2, respectively.
The mean HbA1c and fasting blood glucose were 8.9±1.7% and 194±80 mg/dL,
respectively. The mean duration of T2DM was 7.3±5.9 years. Ninety-five patients
(79%) were treated with oral agents and 55 patients (46%) were treated with insulin.
Forty-five patients (38%) were in the state of mild obesity with BMI less than 35
kg/m2.

Results:

The follow-up rate were 98% at 1 year, 90% at 2 years, 73% at 3 years, 66% at 4
years and 50% at 5 years. The mean BMI at 1, 2, 3, 4, and 5 years were 27.2±5.0
kg/m2, 27.1±5.1 kg/m2, 28.4±5.2 kg/m2, 27.4±5.2 kg/m2 and 28.4±4.8 kg/m2,
respectively. The mean HbA1c at 1, 2, 3, 4, and 5 years were 6.0±1.0%, 6.0±0.9%,
5.9±0.6%, 5.9±0.6% and 5.8±0.7%, respectively. The diabetes remission (HbA1c less
than 6.5% without diabetes medication) at 1, 2, 3, 4, and 5 years were 75%, 75%,
71%, 69% and 73%, respectively.

Conclusion:

LSG-DJB is an effective procedure for achieving weight loss and T2DM remission
and the effects seem to be durable up to 5 years.
WCIDT-0122
Impact of bariatric/metabolic surgery on glycemic control

INSULIN RESISTANCE REVISITED


S. Salinari1, F. Rubino2, A. Bertuzzi3, E. Previti1, C. Guidone4, G. Mingrone4,5,6
1
University of Rome “La Sapienza, Department of Computer- Control-
and Management Engineering, Rome, Italy
2
King’s College London, Chair of Bariatric Surgery, London, United Kingdom
3
CNR, Institute of Systems Analysis and Computer Science, Rome, Italy
4
Catholic University, Department of Internal Medicine, Rome, Italy
5
King’s College London, Diabetes and Nutritional Sciences- Hodgkin Building-
Guy’s Campus, London, United Kingdom
6
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden,
Department of Medicine III, Dresden, Germany

Background: Insulin secretion is much higher when glucose is given orally than
intravenously. We hypothesize that this increased insulin secretion is associated with
a higher insulin resistance to avoid occurrence of hypoglycemia.

Methods: Eight obese subjects, before and after bilio-pancreatic diversion (BPD),
and eight healthy controls received a 75 g oral glucose-tolerance test (OGTT) and an
isoglycemic glucose intravenous infusion (IGIV), that matched the plasma glucose
concentrations obtained during OGTT. Insulin sensitivity (SI) and secretion were
assessed by the glucose minimal-model. Monte Carlo simulations with the
parameters of OGTT, but with random SI values in the range of SI found during IGIV,
were performed.

Findings: In obese subjects SI was lower (SI×104: 0·27±0·06 vs. 0·91±0·26 min-
1
×pM-1, P=0·039) while insulin secretion was larger (135·63±28·30 vs. 59·44±20·18
nmol, P=0·039) in OGTT compared with IGIV. BPD eliminated this discrepancy
(SI×104: 2·41±0·37 in OGTT vs. 2·70±0·55 min-1×pM-1 in IGIV, P=NS), with SI similar
to that of controls (SI×104: 2·03±0·20 in OGTT vs. 2·69±0·22 min-1×pM-1 in IGIV,
P=NS). After BPD insulin secretion decreased, although it remained larger when
glucose was given orally than intravenously (26·44±7·22 in OGTT vs. 12·92±3·40
nmol in IGIV, P=0·031). The simulations showed that if OGTT SI is set to IGIV value
then hypoglycemia occurs.

Interpretation: To match a higher insulin secretion, oral glucose administration


determines a degree of insulin resistance higher than in an isoglycemic intravenous
glucose infusion. We propose a new idea of insulin resistance, which is viewed as a
physiological mechanism maintaining homeostasis after nutrient intake, acutely
modulated. Glucose utilization would result from the balanced secretion of insulin and
hormone/s opposing the insulin action, while unbalanced secretion would result in
insulin resistance.
WCIDT-0123
Impact of bariatric/metabolic surgery on glycemic control

DYNAMIC CHANGES OF INSULIN SENSITIVITY AND SECRETION AFTER


SLEEVE GASTRECTOMY
G. Casella1, E. Soricelli1, L. Castagneto-Gissey1, A. Redler1, N. Basso1,
G. Mingrone2,3,4
1
Medical School "Sapienza" University, Surgical Sciences Department, Rome, Italy
2
Catholic University of Rome, Departments of Internal Medicine, Rome, Italy
3
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden,
Medizinische Klinik und Poliklinik III, Dresden, Germany
4
King’s College London, Department of Diabetes and Nutritional Sciences-
Faculty of Life Sciences and Medicine, London, United Kingdom

Objective: We aimed at investigating the dynamic changes in insulin sensitivity and


secretion after sleeve gastrectomy (SG).

Summary Background Data: Very few studies investigated insulin secretion after
SG and no data are reported in the literature regarding the changes over time of
insulin secretion and sensitivity after SG.

Methods: We investigated whole body insulin sensitivity by the euglycemic


hyperinsulinemic clamp (EHC) and insulin secretion by C-peptide deconvolution after
an Oral Glucose Tolerance Test (OGTT) before and 3, 6 and 12 months after SG in
10 morbidly obese subjects. Glucagon peptide 1 (GLP1) time course following the
OGTT was assessed.

Results: Baseline insulin sensitivity (M value: 73.80±12.06 mmol/kg/min)


progressively improved up to values of 127.80±7.92 mmol/kg/min (P<0.0001) at 12
months after SG. Fasting insulin sensitivity as HOMA-IR, that represent an index of
hepatic insulin resistance, decreased from 3.69±0.41 to 1.07±0.14 (P<0.0001).Total
insulin secretion after OGTT progressively decreased from 294.69±54.59 at baseline
to 156.06±22.67 mmol/l ∙ 180 minutes at 12 months. The plateau in the above
variables was reached at 6 months after surgery.

GLP1 area-under-the curve (AUC) after the OGTT significantly (P<0.0001) increased
from 296.30±51.67 at baseline to 5628.75±296.55 ∙ 180 minutes pmol/l at 12 months
after SG.

In a multiple regression analysis with M value as dependent variable and weight and
GLP1 AUC as independent ones, 51% (P<0.0001) of the M value variability was
explained by GLP1 secretion (GLP1 β=0.71, P<0.0001; weight β=-0.34, P=0.303).

Conclusions: SG highly improves insulin sensitivity and reduces insulin secretion in


the first six months after surgery, these parameters remain thereafter stable at least
up to 1 year after the operation. Although there is a significantly high correlation of
insulin sensitivity with body weight, the major driver of insulin sensitivity improvement
is GLP1.
WCIDT-0130
Impact of bariatric/metabolic surgery on glycemic control

PRELIMINARY RESULTS OF A RANDOMISED STUDY COMPARING


HYPOGLYCAEMIC EPISODES AFTER GASTRIC BYPASS AND SLEEVE
GASTRECTOMY
E. Capristo1, V. Spuntarelli1, L. Marini1, M. Raffaelli2, A. Iaconelli1, C. Callari2,
C. Guidone1, R. Bellantone2, G. Mingrone1
1
Università Cattolica del Sacro Cuore, Internal Medicine, Roma, Italy
2
Università Cattolica del Sacro Cuore, Surgery, Roma, Italy

Background: Roux-en-Y Gastric Bypass (RYGB) and sleeve gastrectomy (SG) are
the most frequently performed metabolic surgery procedures. Reactive
hypoglycaemia is mainly reported as a late complication of RYGB with respect to SG,
but data in the literature are scarce.
Here we report the preliminary data at 6 months after surgery of a randomised trial
comparing the incidence of hypoglycaemia after RYGB or SG.

Methods: Forty-one non diabetic subjects were enrolled in the study and randomly
assigned to receive either RYGB (n:25; 8M/17F, BMI 43.2±8 kg/m2) or SG (n:16;
4M/12F; BMI 41.1±8.1 kg/m2). Clinical and laboratory examination and Oral Glucose
Tolerance Test (OGTT) were performed before, 1, 3 and 6 month after surgery. The
threshold of blood glucose under 70 mg/dl during the OGTT was considered as index
of reactive hypoglycemia. The six-months risk (cumulative incidence) of
hypoglycaemia was assessed in the 2 groups of subjects.

Results: The 2 groups were comparable for anthopometric characteristics and


baseline glucose and insulin levels. After surgical procedures, we estimated a 43%
six-month cumulative incidence of reactive hypoglycaemia in the SG group, and 70%
in the RYGB group. Plasma glucose was <70 mg/dl in 20 cases, <60 mg/dl in 8 cases
, <50 mg/dl in 9 cases and <40 mg/dl in 2 cases. Reactive hypoglycaemia appeared
at 1 month and further increased during the first 6 months after surgery.

Conclusions: Our data show a much stronger association of RYGB and reactive
hypoglycaemia with respect to SG. Long-term studies are needed to better elucidate
this association.
WCIDT-0136
Impact of bariatric/metabolic surgery on glycemic control

THE EFFECT OF LAPAROSCOPIC SINGLE ANASTOMOSIS GASTRIC BYPASS


ON TYPE 2 DIABETES MELLITUS
M.M. Ozmen1, T.T. Sahin1, S. Isgandarova1, C. Allahverdiyev1, E. Guldogan2
1
Hacettepe University Medical School, Department of Surgery, ANKARA, Turkey
2
Ankara Numune R&T Hospital, Department of Surgery, Ankara, Turkey

Objectives

Laparoscopic single anastomosis gastric bypass(LSAGB) started to become popular


and is preferred in patients who have body mass index over 50kg/m2 or concomitant
systemic diseases such as diabetes.We aim to evaluate the effect of LSAGB on Type
II diabetes(T2DM).

Methods

Patients who underwent LSAGB in two years period were analyzed in terms of
remission of T2DM and related parameters.

Results

183(43M)patients with a mean age of 50(29-62)years underwent LSAGB with a follow


up period of 18(2-26)months. Hospital stay was 4.5(4-7)days. 110(30M)patients were
diabetic and 73(13M) patients were non-diabetic. Mean body weight of the diabetic
patients was 139(102-220)kg. At the end of the follow up period, mean body weight
dropped to 86(65-130)kg.

Of the 110 patients with T2DM; 62(56%) were on oral anti-diabetic and 48(44%) were
on insulin. Mean preoperative blood glucose level of 152(111-250)mg/dl was dropped
to 84(70-160)mg/dl in one year. HBA1C dropped from 9.1% to 5.1%. Furthermore,
preoperative serum insulin and C-peptide dropped to 10.1(3.8-29.5)IU/mL and 3.3(1-
6,5)U/mL.

Drug requirements in diabetic patients were eliminated with LSAGB. Only 3patients
needed oral anti-diabetics for 3 months which gradually subsided and these patients
also became drug free. Insulin dosage was dropped gradually and stopped at 1 year
in one patient and the other patient is still on low dose insulin.

Conclusion

LSAGB seems to be very effective in weight loss and resolution of comorbidities, has
a better safety profile and technically less demanding than other types of gastric
bypass procedures in diabetes. Therefore it might be the procedure of choice for
patients with severe obesity and T2DM.
WCIDT-0152
Impact of bariatric/metabolic surgery on glycemic control

MID-TERM DIABETES REMISSION AFTER ROUX-EN-Y GASTRIC BYPASS


P. Vasas1,2, W. Al-Khyatt2, S. Awad2, I. Idris2, P. Leeder2, A. Awan2, J. Ahmed2
1
Doncaster Royal Infirmary, Bariatric Surgery Unit, Doncaster, United Kingdom
2
East Midlands Bariatric and Metabolic Institute, Bariatric Surgery, Derby,
United Kingdom

Background: Laparoscopic Roux en-Y gastric bypass (LRYGB) has emerged as a


therapeutic option for type 2 diabetes mellitus (T2DM). However, there is a paucity of
data on the effects of LRYGB on T2DM beyond 2 years. This study aimed to analyse
medium-term effects of LRYGB on T2DM and to determine predictors of remission.

Methods: Data on consecutive diabetic patients who underwent primary LRYGB


between September 2009 and November 2010 were collected prospectively. T2DM
outcomes were classified according to the American Diabetes Association guidelines.
Remission : no medication with HbA1C <42 mmol/mol (Complete, CR) or HbA1c 43-
48 mmol/mol (Partial, PR). T2DM was considered improved when there was >50%
reduction in the dose of medications. The effects of baseline characteristics, length
and treatment of T2DM, weight changes (EWL%, BMI) at 4-years on T2DM resolution
were studied.

Results: 46 patients with T2DM underwent LRYGB with mean±SD age and BMI of
48.6±9.6 years and 50.4±6.5 kg/m2, respectively. Median (IQR, interquartile range)
duration of T2DM was 60 (36-126) months. Median (IQR) follow up was 52 (50-57)
months. T2DM resolution was achieved in 64% of patients (CR = 44%, PR =20%),
and further 28% of patients had improvement in their T2DM. Four patients (8%) had
no change in diabetes status. On statistical analysis, significant EWL (p = 0.002) and
lower BMI (p = 0.027) at 4-years were the only independent clinical predictors of
medium-term T2DM outcome.

Conclusion: In this study, LRYGB seems to offer excellent medium-term T2DM


resolution. Moreover, significant EWL and lower BMI were predictors of T2DM
remission.
WCIDT-0156
Impact of bariatric/metabolic surgery on glycemic control

PREOPERATIVE STIMULATED C-PEPTIDE LEVELS DO NOT PREDICT


IMPROVEMENT OF GLUCOSE METABOLISM IN T2DM PATIENTS AFTER
GASTRIC BYPASS SURGERY
E. Svehlikova1, T. Pieber1, A. Tuca1, B. Obermayer-Pietsch1, O. Freisinger2,
F. Tadler3, B. Ernst4, B. Wilms4, M. Thurnheer4, B. Schultes4
1
Medical University of Graz, Department of Internal Medicine-
Division of Endocrinology and Metabolism, Graz, Austria
2
Medical University of Graz, Department of Surgery, Graz, Austria
3
Krankenhaus der Elisabethinen, Department of Surgery, Graz, Austria
4
eSwiss Medical & Surgical Center, eSwiss Medical & Surgical Center, St. Gallen,
Switzerland

Roux-en Y gastric bypass (RYGB) improves glycaemic control in obese patients but
not all patients benefit to a similar extent. The degree of beta cell dysfunction is
supposed to predict the postoperative type 2 diabetes (T2DM) remission. Our study
compared the changes in beta cell function and insulin sensitivity after RYGB
between obese T2DM patients with preoperative low vs. high peak C-peptide
response to an oral glucose tolerance test (OGTT).
Beta cell function and insulin sensitivity was examined before, 8 to 21 days, and 1
year after the surgery in 34 T2DM patients (17 patients with peak C-peptide ≥ 6.18
ng/ml) by an OGTT and an intravenous glucose tolerance test followed by a
hyperinsulinaemic-euglycaemic clamp.
After surgery HbA1c, fasting and OGTT 2-hour plasma glucose levels decreased
similarly in both groups (time p<0.001, interaction ns.). The high-C-peptide group
showed higher fasting C-peptide preoperatively (p<0.01), but displayed a greater
reduction after surgery (interaction p<0.05) resulting in similar values in both groups
by1 year. Both groups showed a comparable increase in C-peptide secretion during
the OGTT early after surgery (p <0.01). One year post-OP, however, the preoperative
high-C-peptide group showed reduced peak and AUC C-peptide in OGTT, while in
the low-C-peptide group respective values were increased (interaction time x group
p<0.01). Insulin sensitivity markedly improved after the surgery with no differences in
respective changes between the two groups.
Our data indicate that preoperative stimulated C-peptide levels do not predict the
degree of improvement in glucose control in T2DM patients after RYGB surgery.
WCIDT-0160
Impact of bariatric/metabolic surgery on glycemic control

PREDICTION OF EARLY DIABETES REMISSION AFTER GASTRIC BYPASS: A


DIRECT STUDY
J. Ried1, G. Baud2, V. Raverdy2, J. Gassenhuber1, F. PATTOU2
1
Sanofi-Aventis Deutschland GmbH,
Translational Med & Early Clinical Global Diabetes Division, Frankfurt, Germany
2
Lille University Hospital, Endocrine and Metabolic surgery, Lille, France

Introduction: Our aim was to systematically compare previously published models


for prediction of diabetes remission after Roux-en-Y gastric bypass (RYGB) and to
identify the best model based on the proposed parameters. Finally, our results are
integrated in a simple tool that can be used to identify patients who can safely stop all
antidiabetic medications immediately after RYGB .

Methods: Glycemic control was assessed in 170 consecutive T2D patients


undergoing RYGB at baseline, after 3 (M3) and 12 months (M12). We compared nine
logistic regression approaches that are published for predicting T2D remission after
RYGB. We then applied stepwise forward selection to identify from all baseline
parameters that have been used in these published models a model that includes few
variables but warrants high accuracy. This model was validated it in an independent
cohort of 80 patients with RYGB.

Results: M3 remission was observed in 67 patients (39%) and persisted at M12 in 66


(96%). M3 remission was accurately predicted by 8 out of 9 published models
(AUC=0.76-0.88). Stepwise forward selection for M3 remission revealed a model
including HbA1c, fasting C-Peptide, insulin treatment and number of antidiabetic
treatments (excluding insulin). The AUC of this model (0.89 [0.89-0.9]) was better
than the full model including all parameters (0.87 [0.86-0.88]). The model predicted in
the replication cohort diabetes remission was predicted with a false positive rate of
15.8% and a false negative rate of 16.7%.

Conclusion: Based on only four preoperative parameters, the proposed model can
identify T2D patients who can safely stop all antidiabetic drugs.
WCIDT-0161
Impact of bariatric/metabolic surgery on glycemic control

EFFECT OF BARIATRIC SURGERY ON TYPE 1 DIABETES


L. Chuah1, K. Hunt2, R. Bhatti3, A. Patel4, F. Rubino5, C. le Roux1,6, B. McGowan7
1
Imperial College London, Metabolic Medicine, London, United Kingdom
2
Kings College London, Department of Diabetic Medicine, London, United Kingdom
3
Guys and St Thomas's Foundation Trust,
Department of Diabetes and Endocrinology, London, United Kingdom
4
Kings College London, Hepatobiliary and Upper GI Surgery, London,
United Kingdom
5
Kings College London, Metabolic and Bariatric Surgery, London, United Kingdom
6
University College Dublin, Diabetes Complication research Centre, Dublin, Ireland
7
Guys and St Thomas' Foundation Trust, Diabetes and Endocrinology, London,
United Kingdom

Background: Bariatric surgery reduces weight and improves glycaemic control in


obese type 2 diabetes patients, but our experience on its effect in people with Type 1
diabetes (T1DM) is limited. Here we report a case series of 15 obese patients with
T1DM undergoing bariatric surgery and their 2-3 years follow up outcome.

Method: Data (demographics, HbA1c, BP, insulin usage) were obtained from
retrospective review of electronic record of three academic institutions in London.
Postoperative outcomes were analysed at 1 year and 2-3 year after surgery. Results:
Fifteen patients with T1DM were identified. Baseline characteristics and follow up
data are shown in Table 1. Six patients had Roux-en-Y gastric bypass, six had sleeve
gastrectomy, two had adjustable gastric band, and one had gastric balloon. Twelve of
the 15 patients completed 2-3 years follow up. There was greater than 50% reduction
in insulin requirement at 1 and 2-3 years after surgery (P<0.05), as well as significant
reductions in weight and BMI. HbA1c levels, however, remained unchanged
throughout the study. One patient developed diabetes ketoacidosis (DKA) post
surgery.

Conclusion: Our series shows that bariatric surgery in T1DM does not induce the
same dramatic reduction of glycemia seen in T2DM. However, insulin requirement is
substantially halved after surgery Clear differential diagnosis of T2DM vs T1DM
preoperatively is warranted due to the risk of DKA
WCIDT-0096
Integration of pharmaceutical/surgical therapies and optimisation of glcontrol
post-surgery

ORAL ADMINISTRATION OF LYCIUM BARBARUM POLYSACCHARIDES (LBP)


REDUCES APOPTOSIS IN BLOOD VESSELS OF DIABETIC RAT BRAINS
Y. Zhang1, M.C. Choi1, K.K. Cheung1, K.F. So2, G.L.Y. Cheing1
1
The Hong Kong Polytechnic University, Department of Rehabilitation Sciences,
Kowlooon, Hong Kong- China
2
The University of Hong Kong, Department of Anatomy, Hong Kong Island,
Hong Kong- China

Background

Diabetes mellitus (DM) and hyperglycemia-induced oxidative stress is known to


damage macro and/or microcirculation in the brain, enhance apoptosis, and
ultimately alter blood brain barrier (BBB) integrity.

Lycium barbarum polysaccharides (LBP) is a traditional Chinese medicine. Emerging


evidence has shown that LBP exerted neuroprotective effects by reducing neuronal
apoptosis and oxidative stress in diabetic rats. The present study examined the
effects of LBP on rescuing apoptosis in blood vessels of diabetic rat brain.

Method

Twelve Sprague-Dawley rats (male, 9-11 weeks) were induced DM by intraperitoneal


injection of streptozotocin and were randomly allocated into diabetic (n=6,DM) and
LBP treatment (n=6, LBP) groups. Four weeks after diabetes induction, LBP
(30mg/kg) and PBS was orally administrated daily to LBP and DM groups for 5
weeks, respectively. Besides, age-matched healthy rats were allocated as normal
controls (n=4, NC) without intervention. Throughout the experiment, body weight and
blood glucose were monitored regularly. Brains (n=3 for DM/LBP, n=2 for NC) were
harvested and apoptosis was examined using TUNEL assay. Results were quantified
as TUNEL-positive cells per total cell count in cerebral vasculatures (TUNEL positive
percentage).

Results

Remarkable increase in apoptosis was found in DM brains (21.98±5.28) compared to


NC brains (6.57±3.03). LBP brains exhibited dramatic reduction in apoptosis
(5.90±0.78) compared to DM brains, without significant alterations in body weight and
blood glucose.

Discussion
This is the first study demonstrating that LBP (30mg/kg) administration can rescue
the diabetic-induced apoptosis in cerebral vasculatures. Effects of LBP on BBB
require further investigation.
WCIDT-0121
Integration of pharmaceutical/surgical therapies and optimisation of glcontrol
post-surgery

PROPOSAL AND STUDY DESIGN FOR A USER LED DIET EDUCATION


PROGRAMME FOR PATIENTS WITH TYPE 2 DIABETES FOLLOWING
BARIATRIC SURGERY
F. Gately1, F. Rubino2, C. Grace3
1
Nourish Communication, Communication, london, United Kingdom
2
Kings College Hospital NHS Foundation Trust, Metabolic and Bariatric Surgery,
London, United Kingdom
3
Kings College Hospital NHS Foundation Trust, Department of Nutrition and Dietetics,
London, United Kingdom

Bariatric interventions are effective in achieving remission of type 2 diabetes. A


critical factor contributing to successful long term outcomes and sustained reduction
in metabolic risk is the adoption of post-operative dietary guidelines and the
prevention of weight regain. Whilst evidence suggests that more and better lifestyle
education improves self-management of type 2 diabetes there is variable post-
operative education and support in the UK and limited understanding of patients’
dietary education needs.

Research is needed to identify how improved educational content and novel modes
of delivery could support patients to make sustained changes to dietary habits and
food choices. Findings will inform the design and development of a standardised
evidence based user led dietary education programme and its evaluation and will
have broad application across the bariatric population. This has the potential to make
a substantial contribution to clinical outcomes and patient reported experiences
following bariatric surgery.

Methods: Mixed methodologies will include desk research, focus groups and one-to-
one interviews using standardised questionnaires. Patients will be asked to identify
barriers and areas of need; and to review existing materials and other media and
methods of support to establish those which are considered useful and motivating
and could support behaviour change. Clinicians and dietitians will be asked to identify
their perceptions of patients’ needs, and to consider how best to develop and deliver
a standardised programme. Patients will be recruited through the bariatric surgical
service at Kings College Hospital London and other participating centres and
healthcare workers from national professional bodies.
WCIDT-0147
Integration of pharmaceutical/surgical therapies and optimisation of glcontrol
post-surgery

GLYCEMIC CONTROL STABILITY IN EARLY POST METABOLIC SURGERY


TREATMENT FOR TYPE 2 DIABETES MELLITUS
M. Moreira1, J.C.D. Repka2, G.C.V.F. de Souza3, C.J.F. de Souza4,
W.P. dos Santos4, A. Nolla4, D.D. Ferrarin4
1
Hospital Angelina Caro, Section of GI Metabolic Surgery, Campina Grande do Sul,
Brazil
2
Hospital Angelina Caron, Section of GI Metabolic Surgery-, Campina Grande do Sul,
Brazil
3
Hospital Angelina Caron, General Surgery Department, Campina Grande do Sul,
Brazil
4
Hospital Angelina Caron, Section of Bariatric Surgery, Campina Grande do Sul,
Brazil

Objective: To investigate the clinical impact on glycaemia control by offering surgery


for type 2 diabetes mellitus (T2DM) treatment in a Metabolic Surgery (MS) program
established at a tertiary Brazilian medical center.

Background: MS has been used to improve glycemic control in T2DM patients. MS


centers are growing in a worldwide pattern.

Methods: The MS program was distinguished from the Bariatric Surgery program by
accepting only T2DM patients since both uses the same eligibility criteria for surgery
candidates. Clinical follow-up was assessed in 20 obese T2DM patients submitted to
Gastric Bypass (GB) by analyzing pre and 12 months post-operative data.

Results: MS patients pre-operative average was 38.2 (+/- 4.7) for body mass index
(BMI), abdominal circumference (AC)=122.5cm (+/- 11.1), fasting glycaemia
(FG)=152.2 (+/-48.1), glycated hemoglobin (HbA1c)=7.8 (+/-1.6) and 24.9 (+/- 17.4)
for insulin (INS). All parameters had post-GB improvement with p<0.001 and passed
the normality test. There were no differences among the post-surgery analyzed
further time points. The correlation coefficient (r) was >/=0.9 by comparing BMI with
HbA1c, insulin and AC, r=0.89 between BMI and FG and the correlation of body
weight loss % with HbA1c and insulin showed r=/> -0.9. Oral and insulin therapies
were reduced or discontinued. There was no mortality and only two minor post-
surgery complications occurred.

Conclusion: MS was safe and effective as adjuvant therapy to improve and sustain
stability in glycaemia control up to 12 months follow-up in T2DM patients.

Key words: diabetes, metabolic surgery, diabetes surgery, bariatric surgery


WCIDT-0016
Intestinal glucose metabolism and nutrient sensing

INTACT NEURAL SYSTEM OF THE PORTAL VEIN IS IMPORTANT FOR


MAINTAINING NORMAL GLUCOSE METABOLISM
H. Yamamoto, T. Yamaguchi, S. Kaida, S. Murata, M. Tani
Shiga University of Medical Science, Surgery, Otsu, Japan

There is strong evidence that bariatric surgery can cure not only obesity but also type
2 diabetes mellitus. However, the underlying mechanisms of improved glycemic
control after surgery has not been undetermined yet.
Gastrointestinal hormones including GLP-1 have been thought to play an important
role of improving diabetes. Recent studies have shown that the vagal nerve around
the portal vein is a key signaling relay system between the gut and the brain to
regulate glucose homeostasis. Interestingly, GLP-1 receptor is widely expressed on
nerve terminals within the portal vein. To clarify the role of the portal neural system on
the regulation of glucose homeostasis in physiological condition, we developed
surgical denervation of the portal vein model (DV) comparing with sham (SO) in rat.
There was no significant difference in food intake and body weight between DV and
SO rats before and one week after surgery. All rats regained the preoperative body
weight. DV rats showed increased blood glucose, GLP-1 and insulin levels during
OGTT. DV rats also showed decreased insulin sensitivity.
These data indicate that an intact portal neural system is important for maintaining
normal glucose homeostasis at least partly mediated by GLP-1 and insulin secretion.
WCIDT-0018
Intestinal glucose metabolism and nutrient sensing

XYLITOL INHIBITS-AMYLASE AND-GLUCOSIDASE ACTIVITIES, REDUCES


INTESTINAL GLUCOSE ABSORPTION AND INCREASES MUSCLE GLUCOSE
UPTAKE TO AMELIORATE TYPE 2 DIABETES IN RATS
M.S. Islam1, C. Chukwuma2
1
University of KwaZulu-Natal, Durban, South Africa
2
University of KwaZulu-Natal, Department of Biochemistry, Durban, South Africa

Background/Aims: Recent studies have reported that xylitol, a commonly used


polyol-based sugar substitutes, has anti-diabetic properties however mechanisms
behind this effect is not well understood.

Methods: The effects of xylitol on α-amylase and α-glucosidase inhibition in vitro and
on intestinal absorption and muscle glucose uptake were conducted in an ex vivo
experiment. Additionally, 7-week-old male SD rats were divided into 5 groups: normal
control (NC), normal xylitol (NXYL), diabetic control (DBC), diabetic xylitol (DXYL)
and diabetic acarbose (DBA). A single bolus dose (1 g/kg bw) of either glucose (NC &
DBC) or glucose with xylitol (NXYL & DXYL) or glucose with acarbose (DBA) was
orally administered to rats with 0.05% w/v phenol red as a recovery marker. Animals
were sacrificed exactly 1 h after the dose and gastric emptying and intestinal glucose
absorption index were measured.

Results: Xylitol showed dose dependent inhibition of α-amylase and α-glucosidase


with the highest inhibition at 30% and 40% concentrations. Dose dependent reduction
of intestinal glucose absorption as well as muscle glucose uptake was observed
when significantly so at 40% concentration. Additionally, oral single bolus dose of
xylitol inhibited small intestinal glucose absorption, delayed gastric emptying and
accelerated digesta transit in the GIT compared to the respective controls.

Conclusion: The anti-diabetic effects of xylitol may not only be due to the lower
carbohydrate digestion and glucose absorption from the small intestinal mucosa, but
may also be due to improving insulin action on skeletal muscle, thus increasing
muscle glucose uptake and utilization.
WCIDT-0074
Intestinal glucose metabolism and nutrient sensing

INCREASE IN CIRCULATING BILE ACIDS IN RESPONSE TO CARBOHYDRATE


AND PROTEIN MAY CONTRIBUTE TO SYMPTOMS OF DUMPING AFTER ROUX-
EN-Y GASTRIC-BYPASS
R. Vincent1, D. Taylor1, A. Laurenius2, T. Olbers2, I. Näslund3, J. Karlsson4,
J. Alaghband-Zadeh1, C. le Roux5
1
King's College Hospital, Clinical Biochemistry, London, United Kingdom
2
Sahlgrenska Academy- University of Gothenburg,
Department of Gastrosurgical Research and Education, Gothenburg, Sweden
3
Örebro University Hospital, Department of Upper Gastrosurgical Research, Örebro,
Sweden
4
Sahlgrenska Academy University of Gothenburg,
Institute of Health and Care Science, Gothenburg, Sweden
5
Conway Institute- University College Dublin,
Diabetes Complications Research Centre, Dublin, Ireland

Background: Dumping symptoms occur in patients after Roux-en-Y gastric-bypass


(RYGB) and classified as early of late (late=reactive hypoglycaemia), depending on
timing after meal. We assessed bile acid (BA) secretion and composition post-RYGB
and possible relation to dumping symptoms.

Methods: 18 (14F) patients post-RYGB and 6 (5F) normal weight controls were
recruited based on Dumping Symptom Rating Scale. RYGB group was further divided
into high-dumpers, reactive hypoglycaemia and low-dumpers (all, n=6). All had three
meal [carbohydrate (CHO), FAT & protein (PRO)] challenges on separate days after
an overnight fast. Samples were collected at baseline and every 30min up-to 180min.
BA (15 fractions) were measured and delta BA (Δ; difference between baseline and
maximal response) was calculated. Groups were compared for ΔBA; total (TBA),
primary (PBA), secondary (SBA), 12α hydroxylated (12H) & non-12H.

Results: BMI and % weight loss were similar between the surgical groups. RYGB
groups had exaggerated BA responses to CHO and PRO vs. control but similar
responses to FAT. After CHO; TBA, PBA, 12H & non-12H were exaggerated in
reactive hypoglycaemic and asymptomatic vs. control and SBA in asymptomatic vs.
control. After PRO, TBA, PBA, 12H & non-12H were exaggerated in reactive
hypoglycaemic vs. control. After FAT, responses were similar. In controls BA
responses were exaggerated after FAT vs. CHO and PRO & SBA after CHO vs.
PRO. ΔBA between meal types were similar in RYGB groups.

Conclusion: Post-prandial BA secretion and composition are altered by


different macro-nutrients post-RYGB. This may in part contribute to dumping
symptoms and reactive hypoglycaemia.
WCIDT-0075
Intestinal glucose metabolism and nutrient sensing

DIURNAL RHYTHMS IN THE EXPRESSION OF THE INTESTINAL SUGAR


SENSORS, T1R2/3 AND SGLT3
C. Corpe, P. O'Brien
King's College London, Diabetes and Nutritional Sciences, London, United Kingdom

Introduction: Along the length of the alimentary tract are macronutrient sensors (e,g.
the sweet taste receptor, T1R2/3) that have been implicated in regulating taste
preference, nutrient transport and energy balance. The mechanisms responsible for
regulating their expression is however unknown. Many physiological processes, such
as intestinal sugar transport, exhibit diurnal rhythms that are under the control of
clock genes. We therefore hypothesized intestinal sugar sensors display a diurnal
rhythm entrained by clock genes.

Aims: Identify the intestinal segments where the sugar sensing machinery (T1R2/3,
SGLT3a/b) are expressed and assess diurnal rhythmicity in their expression levels.

Methods: CD-1 mice were fed ad libitum at the standard 12h light/dark cycle. After
six weeks the animals were sacrificed at 7am (n=8) and 7pm (n=8). Tongue,
stomach, duodenum, jejunum & ileum were prepared for RT-qPCR. Expression levels
for each gene were quantified against 3 reference genes using the 2-ΔΔCT method.

Results: T1R2/3 gene expression levels were highest in tongue. T1R3, but not
T1R2, was detected in stomach, and T1R2/3 was detected at low levels in all small
intestinal segments. Conversely, SGLT3a/b expression was highest in more distal
regions of the gut. T1R2/3 gene expression levels demonstrated a modest but
inconsistent diurnal rhythmicity. SGLT3b and SGLT3a showed a robust diurnal
rhythmicity in stomach and small intestine, respectively.

Conclusion: Intestinal sugar sensors, T1R2/3 and SGLT3, are reciprocally


expressed along the length of the alimentary tract. In addition, SGLT3 a/b (but not
T1r2/3) display a diurnal rhythm, which we speculate is under the control of clock
genes.
WCIDT-0006
Mechanisms of action of bariatric and metabolic surgery

MEAL-INDUCED GUT AND PANCREATIC HORMONE PROFILE AFTER SLEEVE


GASTRECTOMY AND GASTRIC BYPASS IN A LEAN ANIMAL MODEL OF TYPE
2 DIABETES
H. Eickhoff1,2, P. Matafome2,3, R. Seiça2,3, F. Castro e Sousa4,5
1
Obesity Center, Hospital de Santiago - Luz Saúde, Setúbal, Portugal
2
Institute for Biomedical Imaging and Life Sciences IBILI, Faculty of Medicine -
University of Coimbra, Coimbra, Portugal
3
Institute of Physiology, Faculty of Medicine - University of Coimbra, Coimbra,
Portugal
4
Department of Surgery A, University Hospital of Coimbra, Coimbra, Portugal
5
Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Background: Changes in gut hormone profile are thought to play an important role in
glycemic control after metabolic surgery but underlying mechanisms remain to be
further clarified. We explored the effect of established bariatric procedures with and
without duodenal exclusion on glycemic control and on gut and pancreatic hormone
profile in a lean animal model of type 2 diabetes.

Methods: We randomly assigned 12- to 14-week-old non-obese diabetic Goto-


Kakizaki (GK) rats to control group, sham surgery, sleeve gastrectomy (SG), and
gastric bypass (GB). Age-matched Wistar rats served as non-diabetic controls (WIC).
We assessed glycemic control at the beginning of the observation period and four
weeks after surgery and measured fasting and mixed-meal induced plasma levels of
ghrelin, GLP-1, PYY, insulin, and glucagon at the end of the observation period.

Results: In GK rats, overall glycemic control improved after SG and GB. Mixed meal-
induced gut hormone profiles in WIC were significantly different from sham operated
or control group GK rats. Both SG and GB induced a similar meal-induced increase in
PYY and GLP-1 and a postprandial decrease in ghrelin as observed in WIC. No
significant effect on plasma insulin could be observed but meal-induced plasma
glucagon increased after SG and GB.

Conclusions: Gut hormones with a neuroendocrine effect like ghrelin, GLP-1, and
PYY in GK rats were significantly modified by SG and GB and become similar to non-
diabetic Wistar rats, but effects of surgery on pancreatic hormones were ambiguous.
Duodenal exclusion alone does not explain changes in gut hormone profile.
WCIDT-0008
Mechanisms of action of bariatric and metabolic surgery

POTENTIAL ROLE OF GASTROINTESTINAL MOTILITY UNDERLYING


MECHANISMS OF IMPROVED GLYCEMIC CONTROL AFTER SLEEVE
GASTRECTOMY

H. Yamamoto1, T. Yamaguchi1, S. Kaida1, S. Murata1, A. Furukawa2, S. Ugi3,


H. Maegawa3, M. Tani1
1
Shiga University of Medical Science, Surgery, Otsu, Japan
2
Tokyo Metropolitan University, Faculty of Health Science-
Division of Radiological Sciences, Tokyo, Japan
3
Shiga University of Medical Science, Internal Medicine, Otsu, Japan

Several possible mechanisms mediating improved glycemic control after sleeve


gastrectomy (SG) have been proposed by animal and human studies. We previously
reported a rapid improvement of glucose tolerance with enhanced GLP-1 and insulin
secretion with markedly increased intestinal motility nicely correlated to GLP-1
secretion during OGTT after SG (PLOS one, 2013). Scintigraphic measurements
showed that gastric emptying is accelerated for solid and liquid meals after SG.
Taken together, these findings suggested that enhanced gastric emptying and
following intestinal motility after SG may accelerate GLP-1 secretion from L cells in
the ileum. Recently, not only gastrointestinal hormones (e.g. GLP-1) but also bacterial
flora and bile acids are suggested to contribute the effects of SG on diabetes.
Bacterial flora and bile acids are affected with gut environment regulated by a meal
and gastrointestinal motility. We will present enhanced intestinal motility using cine
MRI after SG and discuss the role of gastrointestinal motility among several possible
mechanisms mediating improved glycemic control after SG.
WCIDT-0009
Mechanisms of action of bariatric and metabolic surgery

ALTERATIONS IN ENERGY EXPENDITURE IN ROUX-EN-Y GASTRIC BYPASS


(RYGB) RATS PERSIST AT THERMONEUTRALITY
T. Lutz
University of Zurich, Zurich, Switzerland

The compensatory decrease in energy expenditure (EE) in response to weight loss is


attenuated in RYGB rats. The thermoneutral zone (TNZ) is at higher temperatures
than in most housing facilities; hence, rats at room temperature may require an
increased EE due to adaptive thermogenesis. We speculated that reported
alterations in EE of RYGB rats are caused by a shift in the TNZ or reduced thermal
insulation and hence higher thermogenesis. Rats had RYGB or sham surgery. Sham
rats were ad-libitum fed (AL) or weight matched to RYGB (BWM). 4 weeks post-
surgery, EE and body temperature were recorded from 22-32C. EE was higher in AL
and RYGB compared to BWM at all temperatures. In AL and RYGB, EE was lowest
between 28-30C. AL, but not RYGB showed an increase in EE at all other
temperatures. The difference in EE between AL and RYGB rats was smaller at
thermoneutrality than at room temperature. TNZ in BWM rats was between 30-32C;
total EE only increased at 22C but body temperature decreased at temperatures
below the TNZ. Hence, reported alterations in EE of RYGB rats are not due to an
artifact by measuring EE below the TNZ; the TNZ of AL and RYGB did not differ.
However, RYGB rats seemed to have lower requirements for adaptive thermogenesis
below TNZ, suggesting a decrease in heat loss potentially due to reduced tail blood-
flow. While EE was significantly lower in RYGB compared to AL rats at room
temperature, this difference was not significant at TNZ.
WCIDT-0015
Mechanisms of action of bariatric and metabolic surgery

CHANGES IN INTESTINAL GLUCOSE HANDLING COULD EXPLAIN DIABETES


RESOLUTION AFTER ROUX-EN-Y GASTRIC BYPASS
J.B. Cavin1, A. Couvelard2, R. Lebtahi3, K. Arapis4, E. Voitellier1, L. Gillard1,
L. Ribeiro-Parenti4, J.P. Marmuse4, A. Bado1, M. Le-Gall1
1
INSERM, U1149, Paris, France
2
APHP, Department of pathology- Bichat Hospital, Paris, France
3
APHP, Department of nuclear medicine, Paris, France
4
APHP, Department of Surgery, Paris, France

Background

Diabetes resolves rapidly after Roux-en-Y gastric bypass (RYGB) independently of


postoperative weight-loss. Glucose handling by the remodeled gut after surgery could
be a key determinant for diabetes resolution.

Objectives

To evaluate in rats and humans how the remodeled intestine absorbs and consumes
sugar after RYGB surgery.

Methods

Intestinal segments were collected from RYGB or sham obese rats to perform
histological analyses and evaluate expression of sugar transporters. Glucose
transport and consumption were assayed ex vivo using jejunal loops and Ussing
chambers. Histological analyses and immunostaining were performed on formalin-
fixed Roux limb sections obtained from RYGB patients or jejunum from obese
individuals and intestinal glucose uptake was assayed by PET/CT scan imaging.
Statistical analyses used Mann Whitney tests.

Results

In rats and humans; the Roux limb was hyperplasic with increased number of
Ki67- proliferating cells. This overgrowth was characterized by an overexpression
of the sugar transporters Glut1, which is physiologically poorly express in mature
jejunum. Luminal and serosal glucose uptake by the Roux limb was increased in
rats (+150% and +400% respectively vs. sham, P<0.001) suggesting an increased
intestinal glucose consumption. This was confirmed by an increased glucose uptake
by the Roux limb in RYGB patients.

Conclusions
RYGB surgery quickly induces an overgrowth of the Roux limb and increases dietary
and blood glucose consumption by the intestine. The rearranged gut could thus
enhance glucose disposal and contributes to diabetes resolution.
WCIDT-0021
Mechanisms of action of bariatric and metabolic surgery

THE INFLUENCE OF THREE BARIATRIC PROCEDURES ON INSULIN


RESISTANCE IMPROVEMENT SHOULD THE EXTENT OF UNDILUTED BILE
TRANSIT BE CONSIDERED A KEY FACTOR ALTERING GLUCOSE
METABOLISM?
Ł. Kaska, M. Proczko, P. Wiśniewski, Z. Śledziński
Medical University of Gdańsk,
Department of General Endocrinological and Transplant Surgery, Gdańsk, Poland

Introduction: Insulin resistance(IR) the essential step in development of T2DM


resolves quickly after bariatric surgery but the effectiveness depends on the type of
the procedure. Although the long-term influence on IR improvement is well
documented the mechanisms of the ultra-fast response after restrictive and bypass
procedures still require explanation.

Aim: To assess the changes in main parameters of glucose metabolism and to


determine IR evolution from the preparative period to 6 months after the operation,
exposing the ultra-fast postoperative response while comparing the 3 bariatric
methods, with the belief that the metabolic effect may be correlated with anatomical
combinations.

Material and methods: A cohort of insulin resistant individuals recruited to the


prospective study underwent laparoscopic sleeve gastrectomy (SG-30), Roux-en-Y
gastric bypass (RYGB-30) and one-anastomosis gastric bypass (OAGB-30). Main
laboratory parameters of glucose metabolism were evaluated in fasting patients
preoperatively, 4 days and 1, 3 and 6 months after surgery.

Results: Within the whole observation period the most significant improvement in
homeostasis model assessment for IR (HOMA-IR) was observed in the first 4 days
after each operation. The decrease of HOMA-IR was higher (p<0.0001) in gastric
bypass groups than in patients after SG (-41%). The difference between bypass
groups favors OAGB over RYGB (-63 vs. -56% p=0.0489).

Conclusion: Among all bariatric management factors, operation type is the most
important in IR improvement. The significant difference in response after SG vs
RYGB and OAGB supports the concept of metabolic competence of duodeno-jejunal
exclusion. Altered bile flow after duodeno-jejunal exclusion may be responsible for
enhanced glucose metabolism improvement.
WCIDT-0030
Mechanisms of action of bariatric and metabolic surgery

UNRAVELING THE EFFECTS OF ENDOGENOUS INCRETIN HORMONES ON


GLUCOSE METABOLISM AFTER ROUX-EN-Y GASTRIC BYPASS SURGERY
M. SVANE1, K. Bojsen-Moller2, N. Jorgensen2, S. Nielsen2, C. Dirksen2,
V. Kristiansen3, B. Hartmann4, J. Holst4, S. Madsbad2
1
Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
2
Copenhagen University Hospital Hvidovre, Dept. of Endocrinology, Hvidovre,
Denmark
3
Copenhagen University Hospital Hvidovre, Dept of Surgical Gastroenterology,
Hvidovre, Denmark
4
University of Copenhagen, Dept of Biomedical Sciences, Copenhagen, Denmark

Background: Exaggerated glucagon-like peptide-1 (GLP-1) is important for improved


post-prandial glucose metabolism after Roux-en-Y gastric bypass (RYGB), whereas
the role of glucose-dependent insulinotropic polypeptide (GIP) is debated. We
investigated the individual and combined effects of DPP-4 inhibition and GLP-1
receptor antagonism with exendin 9-39 (Ex9) to explore the relative importance of the
endogenous incretin hormones on glucose metabolism after RYGB.

Methods: Twelve glucose tolerant patients (age 35.4±7 (mean ± SEM) years, BMI
33.5±6 kg/m2) were studied 5.3±1 month after RYGB. On four separate days, a
standard mixed meal test (356 kcal) was performed with either 1) placebo (plac); 2)
oral sitagliptin (sita); 3) Ex9 infusion; or combined 4) sita and Ex9 (Ex9/sita) in a
randomized order.

Results: Intact GLP-1 increased 3-fold (p<0.01) and intact GIP 1.6-fold (p<0.01) on
sita days - indicating an effective DPP-4 inhibition. Ex9 infusion increased glucose
excursions compared with placebo; no effect of sita was seen (iAUC glucose: plac
92±44 mmol/L×min, Ex9 192±44 p<0.01, sita 112±43 p=0.47). Insulin secretion rates
(ISR) decreased during Ex9, whereas sita had no effect compared with placebo
(iAUC ISR: plac 933±96 pmol×kg-1, Ex9 713±83 p<0.01, sita 963±123 p=0.95). Ex9
and Ex9/sita had comparable effects on glucose and insulin concentrations (iAUC
glucose: Ex9 192±44 vs. Ex9/sita 163±39, p=0.27, iAUC ISR: 713±83 vs. 660±53,
p=0.65).

Conclusion: GLP-1 receptor antagonism deteriorated glucose tolerance and


impaired insulin secretion, whereas DPP-4 inhibition had no effect. This confirms the
importance of GLP-1 for improved glycaemic control after RYGB, but argues against
a major role of GIP.
WCIDT-0039
Mechanisms of action of bariatric and metabolic surgery

METABOLIC SURGERY - CLINICAL AND MOLECULAR IMPLICATIONS -PILOT


STUDY PRELIMINARY RESULTS
R. Mirica1,2, M. Ionescu1, R. Munteanu3, O. Ginghina1,4, R. Iosifescu1,4, G. Zugravru5,
A. Rosca2, A. Banica6, N. Iordache1
1
'St John'-Emergency Hospital- Bucharest- Romania,
Department of General Surgery II, Bucharest, Romania
2
University of Medicine and Pharmacy 'Carol Davila'- Bucharest,
Department of Phisiology and Neuroscience, Bucharest, Romania
3
Euroclinic Hospital, Department of General Surgery, Bucharest, Romania
4
University of Medicine and Pharmacy 'Carol Davila'- Bucharest,
Department of General surgery- St'John'- Emergency hospital, Bucharest, Romania
5
'St John'-Emergency Hospital- Bucharest- Romania, Department of intensive care,
Bucharest, Romania
6
National Institut of Endocrinology 'C I Parhon', Endocrinology, Bucharest, Romania

Introduction: Obesity is a disorder with many implications both clinical, sistemic and
molecular.Overweight and obese patients are significantly associated with
diabetes.The prevalence of diabetes is a continuous increase among obese patients.

Objectives: The aim of this study is to analyzes the impact of bariatric surgery in
paralel on a model of obese and diabetic rats and on patients who have undergone
surgery for obesity and had also diabetes.

Methods and materials: In this study the aim is to build an experimental part with
obese and diabetic rats (40 rats divided into 4 groups) and a clinical part of patients
presenting obesity associated with diabetes who have undergone surgery for
obesity.The results are preliminary,of a pilot study in which a part of the experiment
conducted on rats was realized.

Results: Preliminary experimental results showed that intestinal


anastomoses(gastro-jejunal and jejuno jejunal) are very safe in terms of
postoperative complications(bleeding and fistulas).In 16 cases(rats that had
undergone gastric bypass)there was only one case of perianastomotic abscess.

Current literature certifies that gastric bypass is the most efficient in terms of weight
loss and maintenance.Further,study aims to examine the therapeutic benefit of
bariatric surgery in terms of glycemia,ghrelin,MMP-2 and MMP-9,weight loss and
food intake in obese Wistar rats that underwent gastric bypass.Correlation of pre-and
postoperative glycemia levels,food intak and ghrelin status with changes in molecular
MMP-2 and MMP-9,it is very current and is olso little researched.
Conclusions: The study demonstrates the benefits of gastric bypass on obesity and
diabetes,and show the changes occurring on extracellular matrix in these cases.
WCIDT-0053
Mechanisms of action of bariatric and metabolic surgery

GASTRIC BYPASS RATHER THAN SLEEVE GASTRECTOMY ALTERS DISTAL


GUT MICROBIOTA
Y. Shao1, B. Xu1, Q. Yao1
1
Huashan Hospital of Fudan University, Center for Obesity and Metabolic Surgery,
Shanghai, China

Background
Gut microbiota is associated with weight-loss after Roux-en-Y gastric bypass
(RYGB). Meanwhile, Sleeve gastrectomy (SG) also gains similar popularity as RYGB
worldwide. However, changes of gut microbiota after SG largely remain unknown.
Objective of this study is to compare the influence of RYGB and SG on distal gut
microbiota.

Methods
Eighteen non-obese rats were randomly divided into RYGB, SG and sham group.
Fecal samples were collected before and 1,3,6,9 weeks after surgery. Distal gut
microbiota was profiled by 16S ribosomal DNA gene sequencing.

Results

1. Weight of RYGB and SG group rats was significantly less than sham group rats
every week after surgery. Meanwhile, weight of SG group rats began to
increase since the second week after surgery, whereas RYGB group rats
remained at a lower level.
2. Shift of microbial composition after RYGB was persistent over time and different
from that of the SG and sham group. SG group rats presented a similar shift
of microbial composition as the sham group rats.
3. Compared to preoperative level, RYGB group rats had persistent increase in
the relative abundance of Gamaproteobacteria (Aggregatibacter) and
decrease in shannon index, while SG group rats only had these changes
within one week after surgery. The relative abundance of Gamaproteobacteria
was negatively correlated with weight whereas shannon index was positively
correlated.

Conclusion
It was RYGB rather than SG altered distal gut microbiota. Gamaproteobacteria may
be one of the potential contributors to the stable weight-loss after bariatric surgery.
Further studies are needed to explore the influence of SG on gut microbiota of obese
host.
WCIDT-0087
Mechanisms of action of bariatric and metabolic surgery

INCREASED CIRCULATING MAGNESIUM CONCENTRATIONS IN TYPE 2


DIABETIC PATIENTS AFTER GASTRIC BYPASS SURGERY
A. Haenni, H.E. Johansson
Uppsala university, Public Health and Caring Sciences, Saeter, Sweden

Background: Low circulating magnesium concentrations are associated with an


increased risk for sudden cardiac death and predict cardiovascular and all-cause
mortality, also when added to the conventional CVD risk factors in type 2 diabetes
(T2DM) patients. Epidemiological and clinical studies have shown lower extra- and
intracellular magnesium concentrations in diabetic subjects.

Aim: To investigate alterations, if any, in circulating magnesium concentrations (p-


Mg) after gastric bypass surgery (GBP) in obese patients with T2DM compared with
nondiabetics.

Method: 173 patients, 120 women and 53 men, all caucasians, recruited from
Skoenvikt Out-patient Clinic of Obesity, Saeter, Sweden.

All patients were treated with GBP and were given the same kind of dietary advice
and multivitamin and mineral supplementation after surgery.

Results: Before surgery the T2DM patients (n=65) showed lower p-Mg compared to
non-diabetic patients, 0.78 (±0.01) and 0.82 (±0.01) mmol/L, respectively (p < 0.001).
The p-Mg was inversely correlated to fasting blood glucose and HbA1c levels.

During the one year follow up weight and BMI fell equally in T2DM and non-diabetics,
by 28%. The fasting glucose concentration and HbA1c fell by 26% and 29% in T2DM
and by 8% and 12% in non-diabetics, respectively.

The mean p-Mg increased in the T2DM group by 5.4%, from 0,80 to 0,83 mmol/L as
compared to 1,5% in non-diabetics (p<0.01). The alterations in p-Mg were inversely
related to the changes in fasting glucose concentration and HbA1c.

Conclusion: The lowered p-Mg, associated with impaired glucometabolic status in


T2DM, was increased, reaching similar concentrations as in non-diabetic subjects
after GBP.
WCIDT-0097
Mechanisms of action of bariatric and metabolic surgery

RELATIONSHIP BETWEEN MUSCLE/ADIPOSE TISSUE MORPHOLOGY,


INSULIN SENSITIVITY AND &SZLIG;-CELL FUNCTION IN DIABETIC AND NON-
DIABETIC MORBIDLY OBESE PATIENTS: EFFECT OF BARIATRIC SURGERY
S. Camastra1, R. Berta2, A. Vitali3, A. Gastaldelli4, R. Bellini5, S. Frascerra1,
B. Astiarraga1, S. Cinti3, M. Anselmino2, E. Ferrannini1
1
University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy
2
Santa Chiara Hospital, Bariatric Unit Surgery, Pisa, Italy
3
University of Ancona, Dept of Molecular Pathology, Ancona, Italy
4
CNR, Institute of Clinica Physiology, Pisa, Italy
5
Santa Chiara Hospital, Bariatric Surgery Unit, Pisa, Italy

Bariatric surgery improves insulin-resistance (IR), lipolysis, ß-cell function (ß-GS),


tissue inflammation. Our aim was to relate the metabolic status after Roux-en-Y
gastric bypass (RYGB) to the morphological changes of subcutaneous (SAT) and
visceral fat (VAT) and skeletal muscle.

Methods: In 14 type-2-diabetic (T2D) and 14 nondiabetic(ND) obese-patients, we


measure IR (by clamp), lipolysis (by 2H5-glycerol), ß-cell glucose-sensitivity (ß-GS,
by mixed-meal), VAT, SAT and rectus-abdominis pathology by light/electron
microscopy (LM/EM) before and 1year after RYGB.

Results: Before surgery, all patients showed marked IR and lipolysis; ß-GS was
impaired in T2D. Adipocyte area and crown-like structures (CLS) were similarly
increased in both groups in SAT and higher in T2D in VAT. On EM, SAT and VAT
showed necrosis, fibrosis, degenerating cells, small mitochondria; in T2D, blood
capillaries contained neutrophils. Intramyocellular fat was higher in T2D. After RYGB
(33% weight-loss), IR and lipolysis were improved in both groups(p<0.003 for all). In
T2D, ß-GS was improved(p=0.04) but not normalized. Fat infiltration was reduced in
all muscle locations(p<0.03) as were adipocyte-area and CLS-density in
SAT(p<0.0001); adipocytes were smaller, delipidated, richer in mitochondria. In T2D,
capillaries were free of neutrophils. SAT adipocyte-area and CLS-density were
related to BMI, IR and lipolysis(r=40-0.81, p<0.0001). ß-GS was related to CLS-
density and intramyocellular fat(r=0,46-0.53, p<0.02).

Conclusion: In morbid obesity, fat and muscle pathology track closely with IR and
lipolysis; in VAT, histology is worse in T2D and correlates with ß-cell dysfunction.
After RYGB, AT/muscle histology and IR improve in parallel; in T2D, ß-GS remains
abnormal despite the restoration of tissue morphology
WCIDT-0125
Mechanisms of action of bariatric and metabolic surgery

SLEEVE GASTRECTOMY FAILS TO IMPROVE GLUCOSE HOMEOSTASIS IN


LIPOCALIN PROSTAGLANDIN D2 SYNTHASE (L-PGDS) KNOCKOUT MICE
R. Lau1, S. Kumar2, C. Hall2, T. Palaia2, K. Hall3, C. Brathwaite3, L. Ragolia2
1
Winthrop University Hospital, Department of Bariatric Surgery-
Department of Endocrinology, Mineola, USA
2
Winthrop University Hospital, Biomedical Research, Mineola, USA
3
Winthrop University Hospital, Department of Bariatric Surgery, Mineola, USA

Background: One quarter of obese type 2 diabetics that undergo sleeve gastrectomy
(SG) achieve diabetes remission. Proposed mechanisms include caloric restriction,
alteration in gut hormone, microbiota, and elevation in bile acid levels. We recently
demonstrated an elevation of an associated bile acid binding protein, lipocalin-type
prostaglandin D2 synthase (L-PGDS), following sleeve gastrectomy. L-PGDS is
known to be associated with improved glucose tolerance and insulin sensitivity. We
hypothesize the bile acid binding protein, L-PGDS, has a major role in the metabolic
improvement seen following SG.

Methods: SG and sham surgery was performed in C57BL/6 (n=3, 3) and L-PGDS
knockout (KO) mice (n=3, 3). Both an oral glucose tolerance (OGTT) (2g/kg) and
intraperitoneal glucose tolerance test (IPGTT) (1 g/kg) was performed at 10 weeks
post surgery.

Results: At 10 weeks post surgery, weights of C57BL/6 mice that underwent VSG
were unchanged as compared to sham controls (38.8 +/- 4 , 41.2 +/- 3 g in SG, sham
respectively). OGTT revealed 2 hour glucose was 138 +/- 5.3 vs 198 +/-22 mg/dL in
SG as compared to sham. IPGTT has a 2 hour glucose of 129 +/- 9 vs 188 +/-37
mg/dL in SG versus sham. In L-PGDS KO at 10 weeks, 2 hour OGTT was 236 +/- 55
mg/dL vs 180 +/- 16 mg/dL in SG versus sham. Weights were similar with SG versus
sham.

Conclusion: Lipocalin Prostaglandin D2 Synthase (L-PGDS) mediates the


improvement in glucose tolerance following sleeve gastrectomy.
WCIDT-0126
Mechanisms of action of bariatric and metabolic surgery

MULTI-TISSUE ANALYSIS REVEALS THE METABOLIC RESPONSE OF MICE TO


RYGB 9 DAYS AND 9 WEEKS POST-SURGERY
D. Ben-zvi1, P. Jane2, T. Siegmund2, L. Meoli3, A. Steuernagel2, N. Stylopoulos3,
D. Melton1
1
Harvard University, Stem Cell and Regenerative Biology, Cambridge, USA
2
Evotec Int., Evotec Int, Goettingen, Germany
3
Boston Children's Hospital, Center for Basic and Translational Obesity Research,
Boston, USA

RYGB leads to favorable metabolic outcomes in obese patients. The surgery often
results in better glycemic control even before weight loss and improves many other
morbidities associated with the metabolic syndrome. The mechanisms that underlie
these positive outcomes are still not fully understood.

We collected tissues from obese mice, 9 days and 9 weeks post RYGB or sham
surgery to study the early and long term effects of this procedure. Transcriptomic
analysis of the duodenum, jejunum, ileum, liver, muscle and fat of operated animals
revealed substantial metabolic reprogramming. We analyzed gene expression
profiles per tissue, and also examined the metabolism of carbohydrates, lipids,
cholesterol and amino acids across tissues.

We identify alterations in metabolite utilization among segments of the intestine. 9


days after surgery, the alimentary limb consumes carbon to build biomass and
displays increased anaerobic metabolism which may be the input for liver
gluconeogenesis. The liver and muscle use lipids as energy source, while adipose
tissue does not increase its lipolysis rate. At the tissue level, we identify a decrease in
duodenal metabolic activity and jejunal proximalization reflecting its adaptation to the
new anatomy. The muscle displays endurance training-like changes in gene
expression, and there are marked changes in liver and adipose tissue metabolism as
well.

Collectively, our data and analysis methods offer insights into the new metabolic state
that ensues following RYGB surgery, and presents an integrative approach to whole
body metabolism and physiology. Furthermore, the study provides leads to discovery
of novel treatments for the metabolic syndrome.
WCIDT-0127
Mechanisms of action of bariatric and metabolic surgery

RESET OF SYNAPTIC FUNCTION IN THE BRAINSTEM NUCLEUS TRACTI


SOLITARII THROUGH SECTION OF THE AFFERENT VAGAL FIBERS: A
MECHANISM OF ACTION OF METABOLIC SURGERY
C. Blasi
Rome, Italy

In the course of metabolic surgery, some of the vagal fibers that connect the intestinal
neuronal network with the vagal centers of the brainstem, are cut. These fibers carry
information about feeding to the brain. They reach the nucleus tractus solitarius
(NTS) where they form synapses with neurons that, in turn, control the pre-ganglion
cells of the dorsal motor nucleus of the vagus (DMV). Through the DMV the activity of
splanchnic organs (like pancreas and liver) are controlled. In situations of protracted
obesity and diabetes, the activity of these afferent fibers is altered. This determines a
change in the activity of the neurotransmitters at synapses in the NTS, due to the
“synaptic plasticity”. The result is an unbalanced activity of vagal control of the
pancreas and liver, determining loss of the double curve of insulin secretion and an
increase in post- prandial glucagon, in addition to an increased and ill-timed hepatic
glucose production (the major dysfunctions of diabetes) (Figure, A). The section of
these fibers during surgery, by interrupting the flow of afferent inputs, causes a reset
of the inter-neuronal transmission in the NTS, especially through the NMDA receptor
(the main actor of synaptic plasticity). The result is the normalization of vagal control
of the splanchnic organs and resumption of their normal activities, followed by
normalization of glycemic control (Figure, B)..
WCIDT-0141
Mechanisms of action of bariatric and metabolic surgery

IMPROVEMENT OF NEUROPATHY AFTER METABOLIC SURGERY: RESULTS


OF AN EMG CONFIRMED PILOT STUDY
A. Celik1, N. Uzun2, A. Kayadibi3, T. Adatepe4, M. Ertas5
1
Turkish Metabolic Surgery Foundation, Metabolic Surgery Clinic, Istanbul, Turkey
2
Istanbul University Cerrahpasa Medical Faculty, Neurology Clinic, Istanbul, Turkey
3
Metabolic Surgery Clinic, Nutrition, Istanbul, Turkey
4
Istanbul Training and Research Hospital, EMG Lab, Istanbul, Turkey
5
Private Office, EMG, Istanbul, Turkey

Background and Aim: In the present study patients with diabetic neuropathy who
have been planned to undergo metabolic surgery have been evaluated by detailed
electromyography before surgery and mean 8 months after surgery. The effects of
glycemic control and the changes in nerve conduction have been analyzed.

Material and Method: The patients consisted of 30 males and 25 females with a
mean age of 52.5 ± 10 and mean diabetic duration of 13.4 ± 7 years. All patients
underwent the same type of surgery (ileal transposition), and they also underwent
preoperative and postoperative (mean 8 ± 2 months) EMG tests evaluating bilateral
sensitive analysis of ulnar, median and sural nerves and motor functions of ulnar,
peroneal, and tibial nerves. The differences between two EMG tests have also been
analyzed.

Results: Before surgery mean preoperative HbA1c was 9.6 ± 2 % and 72.7% of
patients had polyneuropathy. Mean HbA1c decreased to 6.6 ± 2 % and 6.1 ± 3 % at
6th and 12th months, respectively. Postoperative EMG analysis showed improvement
in conduction rates in 55% of the sensitive nerves, and 50% improvement in the
sensitive response rates. Motor response rates have shown 61% improvement in
distal nerve conduction rates, 40% improvement in motor amplitudes, and 57%
improvement in motor nerve conduction rates.

Conclusion: Our results demonstrated marked improvements between preoperative


and mean 8 ± 2 months postoperative EMG measurements in diabetic patients
treated by DSIT. We believe that the significant improvement in glycemic control can
be responsible from this effect on neuropathy.
WCIDT-0142
Mechanisms of action of bariatric and metabolic surgery

THE EFFECT OF BARIATRIC SURGERY ON POSTOPERATIVE GHRELIN


CONCENTRATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
N. Geubbels1, N. Lijftogt2, L.M. de Brauw3, M.J.M. Serlie4
1
Academic Medical Center Amsterdam, Endocrinology and Metabolism, Amsterdam,
Netherlands
2
Leiden University hospital, Surgery, Leiden, Netherlands
3
Slotervaart Medical Center Amsterdam, Metabolic and Bariatric Surgery,
Amsterdam, Netherlands
4
Academic Medical Center- Amsterdam, Endocrinology and Metabolism, Amsterdam,
Netherlands

Background

Ghrelin is a stomach-derived hormone involved in food intake. Studies investigating


the effect of several types of bariatric surgery on ghrelin concentrations show variable
results. This systematic review and meta-analysis aims to evaluate the effect of
several bariatric procedures on ghrelin concentrations at 1, 3, 6 and 12 months of
follow up.

Methods

In December 2014 we searched PubMed and EMBASE. Studies selected for the
meta-analysis included morbidly obese patients who underwent a bariatric procedure
with measurements of ghrelin concentration before and at a specified follow up time
(N=25). Two reviewers screened abstracts for inclusion and assessed study quality
separately. Primary researchers were contacted if necessary. The studies were
pooled and weighted mean differences calculated.

Results

To date, only the results for Roux-en-Y-gastric bypass (RYGB) and total ghrelin
measured with RIA have been analyzed. One month after RYGB ghrelin shows a
mean decrease of -49.63 pg/mL (95%CI:-11.51, 12.26, p=0.12,I2=78%). Three
months after RYGB ghrelin shows a pooled increase of 9.91 pg/mL (95%CI:3.46,
16.36, p=0.003, I2=0%) and six months after RYGB a pooled increase of 7.68 pg/mL
(95%CI: -46.91, 62.27, p=0.78, I2=91%). Twelve months after RYGB mean total
ghrelin increases by 86.65 pg/mL (95%CI: 52.70, 120.6, p<0.001, I2=62%).

Conclusion

This meta-analysis shows that in morbidly obese patients undergoing RYGB the
pooled mean total ghrelin concentration increases ≥3 months after the bariatric
procedure. Since lower ghrelin is associated with a decrease in food intake, this
suggests that ghrelin has no role in surgery-induced weight loss, i.e. lower food
intake.
WCIDT-0144
Mechanisms of action of bariatric and metabolic surgery

MECHANISM OF ACTION OF SLEEVE GASTRECTOMY: DOES SIZE MATTER?


D. Tassinari, J. Casella Mariolo, L. Castagneto-Gissey, E. Giorgakis,
S. Panagiotopoulos1, F. Rubino
King's College London- Denmark Hill Campus, Metabolic and Bariatric Surgery-
Division of Diabetes and Nutritional Sciences- James Black Centre, London,
United Kingdom

Background: It has been suggested that mechanisms of weight loss after


laparoscopic sleeve gastrectomy (LSG) involve restriction of gastric volume and
metabolic effects from the resection of ghrelin-rich fundus. Their relative role,
however, remains unclear. Here we present an unusual complication that allows us to
assess the role of tissue resection against volume restriction.

Case presentation: A 53 years old woman (BMI 68.3 kg/m2) had LSG with complete
resection of the gastric fundus. Intra-operatively, erroneous injection of methylene
blue in the balloon portion of an orogastric tube caused substantial dilation of the
proximal gastric remnant. There were no leaks intra or postoperatively but the patient
developed intramural gastric hematoma and haemoperitoneum requiring blood
transfusions. Postoperative gastrografin X-ray showed major enlargement of the body
of the stomach, distal to the gastro-oesophageal junction. Estimated size and
capacity of the enlarged segment at CT-scan were 50x58 mm and 87 ml respectively.
A barium swallow X-ray was performed 6-month post‐operatively to re-evaluate
stomach size. Six-month percentage weight loss from baseline (WL) was compared
to our uncomplicated LSG cases.

Results: The patient had an uneventful recovery with appropriate reduction of


appetite and meal size. WL was 13, 18 and 24% at 1, 3 and 6-month after surgery,
similar to other LSG patients (11, 17% and 22%). Barium swallow at 6-month showed
persistent enlargement of the remnant stomach.

Conclusion: This case suggests that metabolic effects secondary to resection of


gastric tissue might be more important than volume restriction in the mechanisms of
early weight loss after LSG
WCIDT-0148
Mechanisms of action of bariatric and metabolic surgery

GASTRIC BYPASS SURGERY INCREASES DUODENAL EXPRESSION OF


PCSK2 IN ZUCKER DIABETIC RATS
A. Alami1, P.F. Pedro1, N. Docherty1, C. Le Roux2, R. Drynda2, S.L. Persaud1,
P.M. Jones1, F. Rubino1
1
King's College London- Denmark Hill Campus, Metabolic and Bariatric Surgery-
Division of Diabetes and Nutritional Sciences- James Black Centre, London,
United Kingdom
2
University of Dublin, Dublin, Ireland

Background: Circulating levels of glucagon have been reported to increase following


Roux-en-Y gastric bypass surgery (RYGB). Such glucagon elevation is
counterintuitive for a procedure that cause improvement of diabetes and also
increases levels of GLP-1 and insulin, two factors that typically cause glucagon
suppression in physiologic conditions. Glucagon and GLP-1 derive from the same
gene and result from differential cleavage of preproglucagon by prohormone
convertase 2 (PCSK2). We sought to investigate whether gastric bypass surgery can
induce changes in duodenal PCSK2 expression and preproglucagon processing,
possibly enabling entero-endocrine cells to synthesise and release glucagon.

Materials and Methods: PCSK2 and preproglucagon mRNA levels were quantified
using qRT-PCR in duodenal extracts from diabetic Zucker fa/fa rats that underwent
RYGB (n=6) or a sham operation (n=6). Duodenal glucagon expression was also
investigated using immunohistochemistry.

Results: RYGB caused significant increase in duodenal PCSK2 mRNA and


preproglucagon mRNA compared to sham surgery (p<0.05 for both).
Immunohistochemistry, however, failed to detect significant levels of glucagon in the
duodenum of either RYGB or sham operated animals.

Conclusions: Our findings suggest that RYGB can increase expression of PCSK2 in
duodenal enteroendocrine cells. However, we found no evidence of duodenal
expression of glucagon. Further studies are needed to determine the role of
increased intestinal PCSK2 after gastric bypass.
WCIDT-0163
Mechanisms of action of bariatric and metabolic surgery

METABOLIC SIGNATURES OF ENHANCED FUEL UTILIZATION IN THE


INTESTINE OF HUMAN PATIENTS AND RODENTS AFTER ROUX-EN-Y-
GASTRIC BYPASS SURGERY
L. Meoli1, R. Muñoz2, N. Stylopoulos1
1
Boston Children's Hospital, Center for Basic and Translational Obesity Research,
Boston, USA
2
Pontificia Universidad Católica de Chile, Department of Digestive Surgery, Santiago,
Chile

Roux-en-Y Gastric Bypass Surgery (RYGBS) reprograms the metabolism of the


anatomically reconfigured jejunum of rodents. The intestine, early after RYGBS
undergoes proliferation and tissue remodeling. In response to augmented energetic
needs, it increases sequestration and utilization of key metabolic substrates such as
glucose, cholesterol and amino acids. This metabolic reprogramming may be a key
mechanism of the rapid and sustained control of blood glucose and lipids levels
observed after RYGBS.
We first determined whether the intestine of human patients, following RYGBS,
exhibits the same metabolic rewiring observed in rodents. We examined Roux limb
specimens and compared them to jejunum samples from control obese subjects.
Transcriptome analysis demonstrated an enhancement of pathways involved in cell
cycle, glucose, lipid and amino acid metabolism. Consistently, there was an increase
in the protein expression of key components of these biochemical pathways including
CDK1, a protein essential for cell mitosis, and LDLR. A metabolite profiling of Roux
limb samples further supported the notion that fuel utilization may be increased also
in the Roux limb of human patients. We then sought to determine whether strategies
aiming at enhancing intestinal glucose and lipid metabolism mimic the beneficial
metabolic effects of RYGBS. To this end, we have started to study mouse models,
which specifically replicate the intestinal changes of key metabolic factors induced by
RYGBS (e.g. LDLR overexpression). Preliminary data further support the hypothesis
that intestinal metabolic reprogramming may be a key mechanism for the effects of
RYGBS.
WCIDT-0011
Miscellaneous

USE OF INCRETIN RECEPTOR KNOCK-OUT &BETA;-CELL LINES FOR DUAL


AGONISM DRUG DISCOVERY
J. Naylor1, A. Suckow1, I. Sermadiras2, P. Ravn2, R. Howes2, J. Li2, M. Snaith2,
D. Hornigold1, M. Coghlan1
1
Medimmune, Cardiovascular & Metabolic Disease, Cambridge, United Kingdom
2
Medimmune, Antibody Discovery & Protein Engineering, Cambridge,
United Kingdom

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide


(GIP) are gut peptides secreted in response to food intake that decrease blood
glucose levels by stimulating insulin secretion from pancreatic β–cells. G-Protein
Coupled Receptors (GPCRs) for GLP-1 and GIP are natively expressed in the rat β–
cell line INS1, making it a useful cell line to screen agonists against the receptors at
physiological expression levels. GLP-1 and GIP receptors share downstream
signalling pathways and there are reports of agonists with dual activity at both
receptors (Finan et al., 2013). It is therefore important to distinguish between the
contributions of the two receptors when evaluating new GLP1/GIP dual agonist
molecules as a part of Structure/Activity Relationship (SAR) determination. Selective
antagonists were used to inhibit each receptor to define in vitro pharmacology
however at the high concentrations required for complete blockade, we found the
antagonists to exhibit non-specific effects. For this reason we created a GLP-1 and a
GIP receptor knock out INS1 cell line in which protein for the individual receptors is
completely depleted, which is beneficial over RNA interference. Monoclonal cell lines
harbouring DNA strand breaks were isolated and assayed for receptor absence at the
DNA and protein levels. The downstream production of cAMP in response to GLP-1
or GIP receptor agonism was fully abolished in the respective knock out cell line.
Functional assays clearly demonstrate the utility of such receptor knock-out cell lines
for assessing the specificity and selectivity of dual agonist molecules in an in vitro
screening programme.
WCIDT-0043
Miscellaneous

PHARMACOECONOMIC EVALUATION OF ORAL ANTIDIABETICS ON


DIAGNOSED PATIENTS WITH TYPE 2 DIABETES MELLITUS FROM A CLINIC
OF THE SOCIAL SECURITY MEXICAN INSTITUTE IN MEXICO CITY
F. López-Naranjo1, J. Kravzov-Jinich1, R. Córdova-Moreno1, H. Ortiz-Perez2,
I. Martínez-Barbabosa2
1
Universidad Autónoma Metropolitana - Xochimilco,
Departamento de Sistemas Biológicos, Mexico City, Mexico
2
Universidad Autónoma Metropolitana - Xochimilco,
Departamento de Atención a la Salud, Mexico City, Mexico

Introduction: During a one-year study, it was completed a pharmacoeconomic


evaluation to compare three oral antidiabetics from different therapeutics classes:
Acarbose, Metformine and Glibenclamide, lying on the treatment of ambulatory
patients from a clinic of basic health of the Social Security Mexican Institute in Mexico
City, diagnosed with type 2 diabetes mellitus (DM2), subsequent to a failed
modification of the style life characterized with diet and exercise to control the
hyperglucemic state.

Objective: It was finished a review of therapeutics guides to the treatment of the


DM2 to design the Markov Cycles Tree, based on the Program of Tree Age with the
proposal to appreciate this pharmacoeconomic evaluation. It was considered a
rescue therapy as a double combined therapy (Metformine plus Glibenclamide) in
case of a failed monotherapy characterized by alternative therapies.

Material and Methods: It was completed an evaluation of the total annual costs and
the efficacy of alternative therapeutics and a proposed rescue therapy, in terms of
probability of a successful treatment to reach 7% HbA1C levels. The obtained results
of costs and efficacy were analized with the program called “Markov Cycles Tree”
designed to obtain the cost-effectiveness relationships of alternative therapies
throughout the study period.

Results: Glibenclamide had the lowest cost-effectiveness ($3639/QALY), followed by


Metformine ($3957/QALY) and finally, Acarbose ($5471/QALY) with major frequency
of adverse effects.

Conclusion: The monotherapy with Glibenclamide is the best treatment in terms of


cost-effectiveness, therefore, it could be the most recommended for the initial
pharmacological treatment of patients with DM2.
WCIDT-0061
Miscellaneous

ADIPONECTIN: A POTENTIAL RISK FACTOR OF DIABETIC MYASTHENIA AND


INTERVENTION EFFECT OF CHINESE HERB FORMULA
J. Zhao, M. Xie
Beijing University of Chinese Medicine, Formula, Beijing, China

Background: Skeletal muscle as the major target organ for insulin, plays an
important role in the regulation of energy and material metabolism. Skeletal muscle
dysfunction can cause the development of complication in type 2 diabetes (T2DM).
Such as, excess lipid accumulation in skeletal muscle leads to diabetic myasthenia.
The aim of this study was to investigate that adiponectin induced diabetic myasthenia
by leading to excess lipid accumulation in skeletal muscle, and intervention effect of
Chinese herb formula (CHF) on excess lipid accumulation.

Methods: T2DM was induced by high-fat diet (HFD) and streptozotocin (STZ, 30
mg/kg) and CHF was administered via gavage for 14 days. Serum adiponectin and
skeletal muscle adiponectin receptor, adenosine 5’-monophosphate-activated protein
kinase (AMPK), fatty acid translocase (FAT)/CD36, carnitine palmitoyl transterase-1
(CPT-1) levels were determined by ELISIA kits, as well as skeletal muscle triglyceride
(TG) level was determined by automatic hemorheology analyzer and grip strength
was determined by YLS-13A grip strength meter.

Results: The model animals showed hyperglycemia, hyperinsulinemia; low serum


adiponectin and skeletal muscle adiponectin receptor, AMPK, FAT/CD36, CPT-1
levels; as well as high skeletal muscle TG level and the loss of grip strength.
Administration of CHF (3.4 g/kg for 14 days) significantly decreased fasting blood
glucose (FBG), glycolated hemoglobin (GHbA1c), fasting serum insulin (Fins),
skeletal muscle TG levels, and increased serum adiponectin, skeletal muscle
adiponectin receptor/AMPK/(FAT/CD36)/CPT-1 levels, as well as improved grip
strength.

Conclusions: Adiponectin caused diabetic myasthenia to happen by


AMPK/(FAT/CD36)/CPT-1 pathway, and CHF showed an intervention effect on it.
WCIDT-0063
Miscellaneous

PREOPERATIVE SERUM IRISIN LEVELS WERE ASSOCIATED WITH WEIGHT


LOSS EFFECTS AFTER ROUX-EN-Y GASTRIC BYPASS
Y. Lee1, K. Ju-hee2, H. Yun-suk3, C. Ji-ho1, P. Sunghyouk4, K. Kyung-gon5
1
Inha University Hospital, Family Medicine, Incheon, Korea
2
Inha University Hospital, Clinical Pharmacology, Incheon, Korea
3
Inha University Hospital, Surgery, Incheon, Korea
4
Seoul National University, Pharmacology, Seoul, Korea
5
Gachon Gil Hospital, Family Medicine, Incheon, Korea

Background: Irisin, a humoral factor secreted from muscle (myokine), has been
known to stimulate the program of brown fat development in adipose tissue
(“browning”). Recent animal studies suggested that irisin has possibility to enhance
energy expenditure in obese patients. However, we have limited clinical data to
understand biology of irisin in human, especially in morbidly obese patients taken
bariatric surgery.

Methods: This is a single center, longitudinal, observational study. We recruited thirty


nine morbidly obese subjects (25-56 years, 29.6~45.9 Kg/m2 of BMI) who underwent
Roux-en-Y gastric bypass surgery (RYGBP) and be followed up regularly. In twelve
subjects, fasting serum samples for measuring irisin were collected preoperatively,
and one and nine months after RYGBP. We analyzed the association between irisin
concentrations and clinical change of metabolic characteristics.

Results: Serum irisin concentrations, 1.0115 ± 0.2282 μg/ml ranging from 0.7347 to
1.4928 pre-operatively, altered bidirectionally on one month after RYGBP. In respect
to change of adiposity, pre-operative irisin levels were associated with %EWL at
3months (ß=0.573, R2=0.478, P=0.069) and one year (ß=0.576, R2= 0.612, P=0.04)
after RYGBP.

Conclusions: The Preoperative serum irisin levels were associated with weight loss
effects after RYGBP.
WCIDT-0080
Miscellaneous

DIET OF PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ITS


RELATIONSHIP WITH FOOT INFECTIONS
I. Martínez-Barbabosa1, H. Ortiz-Perez1, R. Romero Cabello2, R. Córdova-Moreno3,
M. Aguilar-Venegas1
1
Universidad Autónoma Metropolitana - Xochimilco,
Departamento de Atención a la Salud, Mexico City, Mexico
2
Hospital General de México, Servicio de infectología, Mexico City, Mexico
3
Universidad Autónoma Metropolitana - Xochimilco,
Departamento de Sistemas Biológicos, Mexico City, Mexico

Introduction: The Type 2 diabetes mellitus (T2DM) complicated with foot infections,
ranks 6th overall morbidity and mortality in Mexico, 4th place worldwide as a direct
and indirect cause of death, and is one of the leading causes of hospitalization.

Objective: Analyze the diet of people with T2DM, before admission to the General
Hospital of Mexico operated by Ministry of Health and its relationship to the
development of foot infections.

Material and Methods: One hundred and fifty patients with T2DM and foot infection
were studied. A questionnaire was conducted to determine the consumption of
cereals, tubers, animal foods, fruits, vegetables, oils and sugars. A medical history of
each patient was filled. Laboratory tests were performed to meet the bacteria causing
infections

Results: The bacteria isolated were Proteus mirabilis, Klebsiella sp, Escherichia coli,
Serratia marcesscens, Enterococcus sp, Staphylococcus aureus, Staphylococcus
epidermidis, Streptococcus β hemolytic and anaerobic bacteria. Patients consumed
55% more carbohydrate (homopolysaccharides, monosaccharides) that lipids and
proteins. Food made of starch (glucose homopolysaccharide) are conducive
hyperglycaemic metabolic imbalance and soft tissues infectious complications. The
greatest risk factor associated with the development of infection was high intake of
simple sugars (sucrose and glucose) p <0.04.

Conclusions: The results indicate that patients with T2DM should not eat simple
carbohydrates such as glucose, and disaccharides such as sucrose. Increased
consumption of fruits and vegetables can prevent metabolic decompensation and
development of diabetic foot infections.

Keywords: Nutrition, Type 2 Diabetes Mellitus, foot infections


WCIDT-0103
Miscellaneous

PIG AS A REPRODUCIBLE LARGE ANIMAL MODEL FOR ASSESSMENT OF


LAPAROSCOPIC ROUX-EN-Y GASTRIC BYPASS EFFECTS ON METABOLIC
SYNDROME
L. Hurtado1, I. Díaz-Güemes1, J.L. De la Cruz2, F.M. Sánchez-Margallo3
1
Minimally invasive Surgery Centre Jesús Usón, Laparoscopy Unit, Cáceres, Spain
2
Clinica San Francisco, Gerneral Surgery, León, Spain
3
Minimally invasive Surgery Centre Jesús Usón, Scientific Director, Cáceres, Spain

Introduction:

The aim of this study is to develop a reproducible model of metabolic syndrome (MS)
and after, a survival model of LYRGB, with similarities to human.

Methods:

Eleven Male Göttingen minipigs (29.52 kg) were induced to MS through a high-fat
high-surcrose diet. After this period, minipigs were subjected to a LRYGB. All animals
underwent a repeated metabolic evaluation (at baseline (T0), after model creation
(T1) and 4 month after surgical procedure(T2)) to assess longitudinal changes in beta
cell function and insulin resistance lipid profile, body condition, adipokines, adipose
tissue distribution. Apart from these, operative time, morbidity and mortality were
registered.

Results:

Body weight, neck and abdominal circumferences, as well as body fat increased
significantly after model creation. Fasting plasma glucose and insulin were increased
in the obesity model and, after surgery, both were decreased. In this context, HOMA-
IR and HOMA-B showed a significant increase after model creation and decrease
after procedure. Adiponectin plasma levels were kept unchanged. Other assessed
parameters (lipid profile) were affected in the same way, increasing at model creation,
as happens in human being. 9 out of 11 pigs survived to the end of the study period.

Conclusion:

We have described a survival porcine model of MS and LRYGBP that can be


reproduced. Gottingen minipig can be an effective model assisting in the evaluation
of the effect of bariatric surgery on body weight and glucose homeostasis. Future
studies isolating the effect of nutrient exposure to specific portions of the gastric
mucosa and distal intestine should help to elucidate more effects.
WCIDT-0140
Miscellaneous

EFFECTIVENESS OF A SOY BASED MEAL REPLACEMENT PRODUCT ON


WEIGHT LOSS AND GLYCAEMIC CONTROL IN OVERWEIGHT AND OBESE
PATIENTS WITH TYPE 2 DIABETES
H. Mccarthy1, S. Koohkan2, A. Berg2, D. Koenig2
1
London Metropolitan University, Public Health Nutrition Research Group, London,
United Kingdom
2
University Hospital Freiburg, Centre for Internal Medicine, Freiburg, Germany

Introduction and objective: Weight loss is important for patients with T2DM prior to
surgery and can help to improve glycaemia. Additionally a liquid meal post-surgery
can provide protein and micronutrients to meet requirements and support the weight
loss process. Almased® is a soy-based meal replacement product. The objective
was to compare Almased® with standard healthy eating/lifestyle advice on weight
loss and glycaemic control in patients with T2DM.

Participants and Methods: 48 overweight/obese patients with diagnosed T2DM,


who were not seeking weight loss surgery and who met the inclusion criteria were
randomised to receive either Almased® or standard health eating/lifestyle advice.
Almased® replaced breakfast or lunch each day for up to 12 months. Healthy
eating/lifestyle advice sessions were delivered monthly. Body weight and composition
and fasting HbA1c, blood glucose and insulin levels were measured at baseline and
after 6 and 12 months. 6 month data are presented.

Results: 11 patients dropped out by 6 months. Weight loss (p<0.03) and decreases
in BMI (p<0.02), body fat (p<0.02) and waist (p=NS) were all greater in the Almased®
group compared with the healthy eating/lifestyle advice group. Improvements in
HbA1c, fasting glucose and fasting insulin were all greater for the Almased® group
but did not reach statistical significance.

Conclusion: These preliminary findings indicated that T2DM patients performed


better by 6 months when consuming Almased®. A larger study with greater statistical
power may confirm these positive benefits and suggest Almased® as an effective
means to promote weight loss and improve glycaemia in patients with T2DM.
WCIDT-0023
Novel technologies and gastrointestinal devices for diabetes

POSTPRANDIAL INSULIN AND INCRETIN RESPONSES AFTER GASTRIC


ELECTRIC STIMULATION (DIAMOND) IN CHINESE OBESE PATIENTS WITH
TYPE 2 DIABETES - A ONE YEAR FOLLOW UP
S. Wong1, A. Kong2, V. Ng3, J. Holst4, E. Ng1, J. Chan2
1
Faculty of Medicine- The Chinese University of Hong Kong, Department of Surgery,
Hong Kong, Hong Kong- China
2
Hong Kong Institute of Diabetes and Obesity- The Chinese University of Hong Kong,
Department of Medicine and Therapeutics, Hong Kong, Hong Kong- China
3
Prince of Wales Hospital, Department of Medicine and Therapeutics, Hong Kong,
Hong Kong- China
4
Faculty of Health and Medical Sciences- University of Copenhagen.,
Department of Biomedical Sciences, Copenhagen, Denmark

Aim: To evaluate the gut hormone response during standard meal test after
implantation of TANTALUS system, a meal-initiated implantable gastric contractility
modulator (GCM) in suboptimally controlled obese type 2 diabetes (T2D) patients.

Patients & Method: Moderately obese (BMI 25-35kg/m2) T2D patients who received
laparoscopic implantation of GCM were followed up and evaluated for changes in
body weight, waist circumference (WC), glycemic control (HbA1C) before and after
treatment. Standard meal challenge test was performed to assess the postprandial
responses of insulin, glucagon like peptide (GLP-1), gastric inhibitory polypeptide
(GIP) and glucagon before and 12 months after treatment.

Results: Eight suboptimally controlled T2DM patients (female = 3) with mean age of
43.9 (SD 10.4) years, mean BMI 29.4 (SD 2.1) kg/m2 and mean HbA1c 9.1% (SD
1.0) received GCM therapy. At 12 months, BW (-3.2±5.2kg, p=0.043) and WC (-
3.8±4.5cm, p=0.021) fell after GCM therapy. At 6 and 12 months, HbA1c fell by
1.6±1.1% and 0.9±1.6% (p=0.011) respectively. Standard meal test showed
significant increases in postprandial insulin secretion at 6 months (area under curve
(AUC), p=0.012) and 12 months (AUC, p=0.028) after surgery. There were also
significant reduction in postprandial glucagon level response (AUC, p=0.017) and
increase in early postprandial rise (15 minutes) of GLP-1 level at 12 months after
surgery (p=0.012), while GIP level remained unchanged.

Conclusion: Our results suggested that GCM implantation improved glycemic


control in obese T2D patients which was associated with increased endogenous
insulin and GLP-1 responses with reduced glucagon production after meal.
WCIDT-0033
Novel technologies and gastrointestinal devices for diabetes

GASTRIC CONTRACTILITY MODULATION: MEDIUM- TO LONG-TERM RESULTS


OF A PILOT STUDY IN OBESE AND NON-OBESE TYPE 2 DIABETIC PATIENTS
F.S. Papadia1, H. Lebovitz2, G.B. Camerini1, A. Belligoli3, C. Flavia1, N. Scopinaro1
1
IRCCS-AOU San Martino-Istituto Nazionale per la Ricerca sul Cancro,
Department of Surgical Sciences and Integrated Diagnostics DISC, Genoa, Italy
2
State University of New York, Health Sciences Center at Brooklyn, New York, USA
3
Impulse-Dynamics, Metacure, Stuttgart, Germany

Background: Up until now only short-term data on Gastric Contractility Modulation


(GCM) in obese and non-obese diabetic type 2 (T2DM) patients have been available.
This study investigates the effect of GCM at longer term in T2DM patients with
insufficient control on oral agents.

Methods: Initial study design focused on glycemic control and weight loss at 25
weeks. The present study investigates glycemic control as indicated by HbA1c,
weight loss and use of antidiabetic medications of implanted patients at their
maximum follow-up.

Results: 20 patients (12 males, 8 females) were enrolled between August 2007 and
October 2009 and implanted with the Diamond System (MetaCure Ltd), without
perioperative morbidity. Mean age was 59 years, BMI: 32.3 kg/m2 (26.8-42.9),
diabetes duration 12.9 years, mean HbA1c 8.89%. One patient enrolled on insulin
has been excluded from the present analysis.

10 patients dropped out (4 conversions to bariatric surgery, 1 explantation at the


patient’s request, 5 patients stopped using the device).

Nine patients with active device and a minimum 5 year follow-up show reduction of
mean HbA1c from 8.2 % to 6.8 % and BMI from 31 to 28 kg/m2. Seven of the 9
patients were on reduced or comparable antidiabetic therapy as compared to their
baseline treatment.

Conclusions: Our experience indicates that type 2 diabetic patients who are
overweight to moderately obese, have HbA1c 10 % or less on oral agents and normal
triglycerides are likely to have significant long-term improvement when treated with
the Tantalus-DIAMOND device.
WCIDT-0048
Novel technologies and gastrointestinal devices for diabetes

GASTRIC CONTRACTILITY MODULATION (GCM) IN THE TREATMENT OF TYPE


2 DIABETES: A RANDOMIZED BLINDED CROSS-OVER STUDY
M. Zelewski1, H.E. Lebovitz2, B. Ludvik3, J. Kozakowski4, W. Tarnowski5, I. Yaniv6,
T. Schwartz7
1
MetaCure Ltd, CEO, Jozefow, Poland
2
State University of New York, Health Science Center at Brooklyn, Brooklyn, USA
3
Krankenanstalt Rudolfstiftung, 1.Medizinische Abteilung, Vienna, Austria
4
Center of Postgraduate Medical Education, Bielanski Hospital, Warsaw, Poland
5
Center of Postgraduate Medical Education, Orlowski Hospital, Warsaw, Poland
6
MetaCure Ltd, CEO, Oramgeburg, USA
7
GCP Clinical Studies, Research Division, Tel-Aviv, Israel

Background:

Gastric Contractility Modulation (GCM) improves glycemic control and decreases


weight and systolic blood pressure in patients with type 2 diabetes inadequately
controlled on oral antidiabetic agents.

Objective:

To determine whether device implantation alone (placebo effect) contributes to the


observed long-term GCM metabolic benefits.

Design:

48 week randomized, blinded, cross-over trial comparing glycemic improvement of


DIAMOND® (MetaCure Ltd) implanted patients with type 2 diabetic with no activation
of the electrical stimulation (placebo) versus meal-mediated activation of the electrical
signal. All implanted patients have been randomized to have the device turned either
“OFF” or “ON” for 24 weeks. Subsequently the device status was cross- over for
next 24 weeks. The endpoint was improvement in glycemic control (HbA1c) from
baseline to 24 and 48 weeks

Results:

In period 1 (0-24 weeks) equal improvement in HbA1c occurred independent of


whether the meal-mediated electrical stimulation was turned on or left off (HbA1c -
0.80 % and -0.85 % (-8.8 and -9.0 mmol/mol). The device placebo improvement
proved to be transient as it was lost in period 2 (25-48 weeks). With electrical
stimulation turned off, HbA1c returned toward baseline values (8.06 compared to
8.32 %; 64.2 to 67.4 mmol/mol). In contrast, turning the electrical stimulation on in
period 2 sustained the decrease in HbA1c from baseline (-0.93 %, -10.1mmol/mol)
observed in period 1.

Conclusion:

Implantation of the DIAMOND device causes a transient improvement in HbA1c


which is not maintained after 24 weeks. Meal-mediated electrical stimulation accounts
for the significant improvement in HbA1c beyond 24 weeks.
WCIDT-0049
Novel technologies and gastrointestinal devices for diabetes

OBESE TYPE 2 DIABETES PATIENTS TREATMENT WITH GASTRIC


CONTRACTILITY MODULATION; NORMAL TRIGLYCERIDES PREDICT
DURABLE EFFECTS FOR AT LEAST 3 YEARS
H.E. Lebovitz1, B. Ludvik2, M. Zelewski3, I. Yaniv4, T. Schwartz5
1
. State University of New York, Health Science Center at Brooklyn, Brooklyn, USA
2
Krankenanstalt Rudolfstiftung, 1. Medizinische Abteilung, Vienna, Austria
3
MetaCure Ltd, CEO, Jozefow, Poland
4
MetaCure Ltd, CEO, Orangeburg, USA
5
GCP Clinical Studies, Research Division, Tel-Aviv, Israel

Background:

Gastric Contractility Modulation (GCM) improves glycemic control, decreases weight


and systolic blood pressure in patients with type 2 diabetes inadequately controlled
on oral antidiabetic agents.

Objective:

To evaluate the long-term benefit of GCM by DIAMOND® (MetaCure Ltd) device on


glycemic control and weight and determine the magnitude of the modulating effects of
plasma triglyceride levels on the metabolic effects of GCM.

Methods:

61 patients with type 2 diabetes were implanted with the DIAMOND® device and
treated with meal-mediated antral electrical stimulation for up to 36 months. The
effects of baseline A1C and fasting plasma triglyceride levels (TG) on glycemic
control, body weight and systolic blood pressure were assessed.

Results:

GCM reduced mean A1C by 0.9 % and body weight by 5.7 %. The effects were
greater in patients with normal plasma triglycerides (NTG) as compared to those with
hypertriglyceridemia. The mean decrease in A1C in NTG patients averaged 1.1 %
and was durable over the 3 years. ANCOVA indicated that improvement in A1C was
a function of both baseline fasting plasma TG (p=0.02) and A1C (p = 0.001) and their
interaction (p=0.01). Marked weight loss (≥ 10 %) was observed in a significant
proportion of NTG patients by 12 months of treatment and persisted through the 3
years.
Conclusions:

GCM improves the metabolic parameters in patients with type 2 diabetes


inadequately controlled on oral agents. A likely mechanism for these effects is
through a gut-brain interaction that modulates effects on the liver and pancreatic
islets.
WCIDT-0081
Novel technologies and gastrointestinal devices for diabetes

DUODENO-JEJUNAL BYPASS LINER IN OBESE T2DM PATIENTS WITH


ADVANCED DISEASE
A. García Ruiz De Gordejuela1, J. Pujol Gebelli1, A. Casajoana Badía1, E.C. Eduard2,
M. Galvao Neto3, N. Vilarrasa García4
1
Hospital de Bellvitge, General Surgery Department,
L´HOSPITALET DE LLOBREGAT, Spain
2
Hospital Universitary Dexeus, Endoscopy Department, Barcelona, Spain
3
Gastro Obeso Center, Endoscopy Department, Sao Paulo, Brazil
4
Hospital de Bellvitge, Endocrinology Department, L´HOSPITALET DE LLOBREGAT,
Spain

Background:

The duodeno-jejunal bypass liner (DJBL) is a new endoscopic device with promising
results. We evaluated the device diabetic obese patients with advanced disease.

Methods:

We indicated the DJBL in patients with very long T2DM evolution or poor glycemic
control. We excluded patients with BMI over 45kg/m2. The device was scheduled for
12 months. We evaluated the evolution of T2DM during the use of the DJBL and
after the retrieval, weight loss and the safety of the device.

Results:

29 patients were indicated for DJBL. 27 had the device retrieved during the study
time (18 had at least 6 months of follow-up after that and 13 one year). 14 were
women with mean age of 51.87 (range 24 to 65). They had an average of 154
months of T2DM duration (5 to 348) and HbA1c was 8.53% (5.4 to 13.10). 83% of the
patients needed insulin. HbA1c improved in 1.22 units at the time of the retrieval with
moderate worsening after that. Following ADA criteria, at the time of the retrieval 2
patient were under partial remission and 9 had improvement. One year later 2
remained under partial remission and 2 with improvement. There were not severe
complications (3 cases of Clavien≤2B and 3 with Clavien 3B) and no mortality.

Conclusions:

In those complex T2DM patients the effect of the DJBL is not as good as in other
patients with better profile. We found one subtype of patients with moderate results,
but the population is too low to take any heavy conclusion.
WCIDT-0104
Novel technologies and gastrointestinal devices for diabetes

DUODENAL MUCOSAL RESURFACING (DMR) AS A NEW ENDOSCOPIC


TREATMENT FOR TYPE 2 DIABETES (T2DM): SAFETY AND PROOF-OF-
PRINCIPLE COHORT STUDY
A.D. Cherrington1, M.P. Galvão Neto2, L. Rodriguez3, P. Becerra3, P. Rodriguez3,
P. Vignolo3, H. Rajagopalan4, J.D. Caplan4, G. Mingrone5
1
Vanderbilt University Medical Center, Molecular Physiology and Biophysics,
Nashville, USA
2
Gastro Obeso Center, Gastrointestinal- Bariatric and Metabolic Surgery, São Paulo,
Brazil
3
CCO Obesidad Y Diabetes, Department of Surgery, Santiago, Chile
4
Fractyl Labs, R&D, Waltham, USA
5
Catholic University of Rome, Department of Internal Medicine, Rome, Italy

Introduction: Bariatric surgeries that prevent nutrients from contacting the


duodenum improve glycemic control in T2DM. DMR, a non-invasive, endoscopic
procedure involving thermal ablation of the duodenal mucosa, potentially offers
similar metabolic benefit.

Objectives: To assess procedural safety and glycemic control after DMR in patients
with poorly controlled T2DM (HbA1c > 7.5% on 1-2 anti-diabetic agents).

Methods: Using novel balloon catheters, we performed thermal ablation on varying


lengths of duodenum in 39 anesthetized patients at a single center (Santiago, Chile):
28 received DMR on a long-segment (~9.3 cm; LS-DMR), 11 received DMR on a
short segment (~3.4 cm; SS-DMR).

Results: Baseline mean HbA1c of 9.5% (SD±1.3) was reduced by 2.5% (SD±1.3) in
LS-DMR and 1.2% (SD±1.7) in SS-DMR at 3 months post-procedure (p<0.05 for LS
vs SS). In 15 LS-DMR subjects with baseline HbA1c of 7.5-10% (mean 8.7%
[SD±0.9]), HbA1c at 6 months was reduced to 7.5% (SD±1.2) despite anti-
diabetic medication reduction in 9 of the patients. Excluding patients with medication
adjustments, HbA1c decreased from 8.5% (SD±0.9) to 7.1% (SD±0.6; p<0.05) at 6
months after LS-DMR, accompanied by a modest weight reduction of 2.3 kg
(SD±3.2). There was no apparent correlation between degree of weight loss and
magnitude of HbA1c improvement. Three patients experienced duodenal stenosis
that required balloon dilation, with good resolution.

Conclusion: Single procedure DMR substantially improves glycemic control in T2DM


with acceptable safety and tolerability.
WCIDT-0135
Novel technologies and gastrointestinal devices for diabetes

A NOVEL LAPAROSCOPIC REVERSABLE GASTRIC BAY-PASS WITH


FUNDECTOMY AND ESPLORABLE STOMACH (LRYGBP FSE)
G. Lesti1, M. Zappa2, F. Altorio1, A. Porta2
1
Clinica Di Lorenzo Avezzano, ., Avezzano, Italy
2
Ospedale Fatebenefratelli Erba, ., Erba, Italy

Background: This novel personal model of laparoscopic gastric bypass(LRYGBPfse)


has a gastric pouch 30-40 cc in volume connected to the remnant stomach by a
channel 2 cm. wide closed with a Gore-The band(polytetrafluorethilene) 5-7 cm.
long and 0.8cm. wide; the remnant stomach can therefore be investigated
endoscopically . Gastric fundus removal allows a decrease in ghrelin and an
increase in PYY and GLP-1.The operation is easily reversible by cutting the band.

Methods: From January 2007 to December 2014, 512 morbidly obese patients
underwent LRYGBPfse; 107 (63 females and 44 males) had type 2 diabetes. Body
weight, fasting plasma glucose, fasting C-peptide and HbA1c were measured in all
patients before surgery and after 1, 3 and 5 years.

Results: Weight loss and mass index decreased in all 512 patients, comparable to
the results of standard LRYGBP. In a sample of 25 morbidly obese patients with type
2 diabetes the fasting ghrelin levels were markedly decreased 6 and 12 months after
the operation. The C-peptide showed a decrease in all patients at 1 month which
persisted in the following measurements . 93% of patients with C-peptide >3 ng/ml.
achieved a complete remission of their diabetes with HbA1c <6.5%. at 1 year, 84%
at 3 years and 78% at 5 years.

Conclusions: This model of gastric bypass with fundus removal decreases the
ghrelin level and increases the PYY and GLP-1 levels. The operation still allows
endoscopic diagnosis and treatment of stomach and biliary tract diseases.
Reversibility is important, above all ,for the non-responder diabetic patients.
WCIDT-0035
Randomized clinical trials comparing surgical procedures head to head for the
treatment of diabetes

BY-BAND-SLEEVE: PRAGMATIC RCT TO EXAMINE THE EFFECTIVENESS AND


COST EFFECTIVENESS OF LAPAROSCOPIC ADJUSTABLE-GASTRIC-BAND,
ROUX-EN-Y-GASTRIC-BYPASS AND SLEEVE-GASTRECTOMY FOR SEVERE
AND COMPLEX OBESITY
R. Welbourn1, J. Byrne2, R. Andrews3, W. Caroline4, J. Donovan4, C. Rogers5,
J. Blazeby4, on behalf of the By-Band-Sleeve TMG5
1
Musgrove Park Hospital, Bariatric Surgery, Taunton, United Kingdom
2
University Hospital Southampton, Bariatric Surgery, Southampton, United Kingdom
3
Musgrove Park Hospital, Diabetes and Endocrinology, Taunton, United Kingdom
4
University of Bristol, School of Social and Community Medicine, Bristol,
United Kingdom
5
University of Bristol, Clinical Trials and Evaluation Unit, Bristol, United Kingdom

The recent Cochrane review of surgery for weight loss highlights the need for good-
quality long-term RCTs to establish evidence for types of surgery for the remission of
diabetes. However RCTs in surgery are often considered to be difficult-to-do because
of preferences that prohibit randomisation. Here we present progress and recruitment
into the NIHR By-Band-Sleeve RCT.

By-Band-Sleeve is a multi-centre RCT with an internal pilot phase. The first part
included a recruitment intervention to establish if randomisation between adjustable-
gastric-band and Roux-en-Y-gastric-bypass (By-Band1) was possible. The
recruitment intervention included audio-recordings of consultations between surgeons
and patients and individual and group training and feedback to establish how to
explain randomisation and balance information provision. Numbers of patients
referred for surgery, eligible for the study and randomised were monitored, and at the
end of the pilot evidence and practice for sleeve-gastrectomy was reviewed.

Initially in two centres in six-months 133 patients were screened, 103 eligible and
only 23 randomised. After training and feedback this increased to 432, 315 and 107
respectively at 18-months. Funding to expand into the main trial was obtained and
based UK sleeve-gastrectomy NSBR data an extension to adapt By-Band to By-
Band-Sleeve funded. Of the 188 patients currently randomised in By-Band alone 70
(37%) have diabetes.

This study shows that it is possible to recruit into difficult-to-do RCTs of types of
surgery for severe obesity including patients with diabetes. By-Band-Sleeve will now
expand into 12 centres and recruit 1341 patients to answer questions of importance
to patients, surgeons and the NHS.

Acknowledgement and Disclaimer

This project was funded by the National Institute for Health Research Health
Technology Assessment Programme (project number 09/127/53). The views and
opinions expressed therein are those of the authors and do not necessarily reflect
those of the HTA, NIHR, NHS or the Department of Health.
WCIDT-0071
Role of bile acids in glucose homeostasis

THE RATIO OF 12&ALPHA;-HYDROXYLATED : NON-12&ALPHA;-


HYDROXYLATED BILE ACIDS IS NOT ALETRED AFTER ROUX-EN-Y GASTRIC
BYPASS IN HUMANS
R. Vincent1, M. Werling2, G. Cross1, L. Fädriks2, H. Lonroth2, D. Taylor1,
J. Alaghband-Zadeh1, T. Olbers2, C. le Roux3
1
King's College Hospital, Clinical Biochemistry, London, United Kingdom
2
Sahlgrenska Academy- University of Gothenburg,
Department of Gastrosurgical Research and Education, Gothenburg, Sweden
3
Conway Institute- University College Dublin,
Diabetes Complications Research Centre, Dublin, Ireland

Background: Roux-en-Y gastric bypass (RYGB) leads to the remission of type 2


diabetes (T2DM) in up-to 40% of patients. Altered bile acid (BA) secretion and
composition may partly contribute to T2DM remission. The enzymes CYP7A1 (rate
limiting) and CYP8B1 (12α hydroxylase) drive the BA pool and composition
respectively. Non-12α hydroxylated (non-12H) primary and secondary BA have
greater affinity to receptors FXR and TGR5 respectively. It has been shown in rats
RYGB reduces hepatic CYP8B1 but does not alter CYP7A1 expression. Insulin
inhibits CYP8B1. We assessed the effect of RYGB on both these enzymes by
measuring changes in BA.

Methods: The prospective study recruited 63 obese individuals (43 F), aged 43 (36-
56) [median (IQR)] years. Blood samples were collected before and every 30min for
120min after a 400 kcal meal before and 15 months after RYGB. BA (15 fractions),
glucagon like peptide-1 (GLP-1), glucose and insulin were measured. Delta (Δ;
difference between baseline and maximal post-prandial response) and HOMA-IR
were calculated.

Results: After RYGB, HOMA-IR decreased 5.9 (3.5-9.2) to 1.7 (1.1-2.2) (p<0.001).
Baseline total BA and GLP-1 increased (p=0.02 & <0.001). Δ total BA and ΔGLP-1
increased (p<0.01 & <0.001). Baseline 12H and non-12H increased (p=0.01 & 0.02),
the 12H:non-12H was similar (p=0.35). There were marked increase in Δ12H and
Δnon-12H (both, p<0.0001), but the ratio was retained p=0.32.

Conclusions: After RYGB the CYP7A1 pathway was up-regulated, however; the
expected suppression of CYP8B1 was notnoted. The increase in non-12α
hydroxylated BA may in part contribute to remission of T2DM after RYGB.
WCIDT-0091
Role of bile acids in glucose homeostasis

EFFECTS OF ORAL ADMINISTRATION OF BILE ACIDS ON GLP-1 SECRETION


AFTER ROUX-EN-Y GASTRIC BYPASS
S. NIELSEN1, M.S. Svane1, K.N. Bojsen-Moeller1, V. Kristiansen2, J.J. Holst3,
S. Madsbad1
1
Copenhagen University/ Hvidovre Hospital, Department of Endocrinology, Hvidovre,
Denmark
2
Copenhagen University/ Hvidovre Hospital,
Department of Surgical Gastroenterology, Hvidovre, Denmark
3
University of Copenhagen, Department of Biomedical Sciences, Copenhagen,
Denmark

Background

Bile acids have been proposed as contributors to improved glycaemic control after
Roux-en-Y gastric bypass (RYGB) by enhancing postprandial GLP-1 secretion
through TGR5-receptor activation. As RYGB changes the gastrointestinal anatomy, it
may be possible to reach L-cells in the distal part of the intestine by an oral route.
Therefore, we evaluated the effects of oral administration of ursodeoxycholic acid
(UDCA) and chenodeoxycholic acid (CDCA) on GLP-1 and insulin secretion in
RYGB-operated patients.

Methods

On three different days 10 RYGB-operated patients (age (mean ± SEM) 37.9 ± 3.4
years, BMI 29.2 ± 1.3 kg/m2, fasting plasma glucose 4.96 ± 0.13 mmol/L) ingested
either 1) UDCA (750 mg); 2) CDCA (1250 mg) suspended in 150mL water; or 3)
150mL water alone (placebo). Blood samples were drawn for the following 180
minutes.

Results

Oral intake of CDCA increased GLP-1 and insulin secretion slightly, but significantly,
compared with placebo (delta GLP-10–peak: placebo: 4.67 ± 1.76 pmol/L, CDCA: 14.81
± 1.39 pmol/L, p = 0.0055; delta C-peptide0–peak: placebo: 45 ± 13 pmol/L, CDCA: 140
± 27 pmol/L, p = 0.0012), while GLP-1 and insulin secretions were unaffected by
UDCA (delta GLP-10–peak: 9.64 ± 2.54 pmol/L, p = 0.11; C-peptide0–peak: 72 ± 13
pmol/L, p = 0.23). Neither UDCA nor CDCA changed plasma glucose.

Conclusion
In RYGB-operated patients with normal glucose tolerance, oral administration of
CDCA increased GLP-1 and insulin secretion significantly compared with placebo,
whereas no effect was seen after oral administration of UDCA.
WCIDT-0024
Role of gut microbiota in metabolism and in the pathophysiology of obesity
and diabetes

MORBID OBESITY AND RACE-RELATED HELICOBACTER PYLORI


COLONIZATION
J. Su, C.H. Tan, A. Cheng
Khoo Teck Puat Hospital, Department of Surgery, Singapore, Singapore

Introduction:

Recent publication has indicated that there is an inverse relation between the
presence of HP colonization and Obesity. We studied this relationship in a cohort of
patients seeking Bariatric Surgery in multi-ethnic Singapore.

Methods:

All morbidly obese patients seeking Bariatric Surgery in a single institution in


Singapore from January 2010 to January 2015 who underwent routine gastroscopy
during their workup process were retrospectively selected. Antral biopsy was
obtained and tested for HP colonization using HP ONE, a proprietary Rapid Urease
test.

During the same period, all patients who underwent OGD for various indications and
who have recorded a similar antral biopsy and HP One Rapid Urease test, were
recorded as a reference for prevailing HP colonization rate.

Results:

There were 158 Bariatric patients of which 21 (15.8%) were HP positive. At the same
period 10170 Rapid Urease tests were carried out and 1607 (15.8%) were HP
positive.

Racial subgroup analysis was then performed, showing that Indians had the highest
HP positivity rates (23.1% in morbid obesity group, 19.7% in other individuals)

Conclusion:

This study presents a significantly lower HP positivity rate than that previously
reported, likely due to different modalities used to define HP colonization i.e. biopsy-
based tests vs sero-positivity. Our finding of no statistically significant result in HP
positivity rate between morbidly obese individuals and other individuals concurs with
that of the 3rd National Health and Nutrition Examination Survey. Racial differences
may play a part in HP positivity and suggest that further studies may be necessary to
elucidate this relationship.
WCIDT-0065
Role of gut microbiota in metabolism and in the pathophysiology of obesity
and diabetes

GUT MICROBIOTA-DERIVED SHORT CHAIN FREE FATTY ACIDS STIMULATE


INSULIN SECRETION FROM MOUSE AND HUMAN ISLETS
A. Pingitore, T. Hill, J. Bowe, G.C. Huang, S. Persaud
King's College London, Diabetes & Nutritional Sciences, London, United Kingdom

Short chain fatty acids (ScFA) are 2-6 carbon fatty acids originating from fermentation
of carbohydrates and fibre by gut microbiota, which act as endogenous ligands of G-
protein coupled receptors FFA2 and FFA3. Changes in gut microbiota composition
modulate ScFA production and diets rich in fermentable carbohydrates improve
glucose homeostasis, but it is not known if direct actions of ScFA at islets contribute
to this. We have studied the effects of sodium acetate (SA; C2) and sodium
propionate (SP; C3), the main circulating ScFAs, on insulin secretion from human (HI)
and mouse islets (MI) via dynamic insulin profiling. Changes in intracellular Ca2+
([Ca2+]i) in Fura-2-loaded islet cells following ScFA treatment were measured by
microfluorimetry. Perifused HI responded with significant and reversible potentiation
of insulin secretion upon exposure to 0.1-1mM SA (20mM glucose: 25.9±3.4
pg/islet/min; +1mM SA: 118.0±12.9, n=5, p< 0.001). Insulin secretion from HI was
also potentiated by 1mM SP, albeit to a lesser extent than with 1mM SA (20mM
glucose: 24.8±1.9 pg/islet/min; +1mM SP: 40.3±6.4, n=5, p<0.05). MI perifused with
SA and SP behaved similarly (20mM glucose: 8.0±0.7 pg/ islet/min; +1mM SA:
11.5±1.6, n=3, p<0.01; +1mM SP: 25.2 ±4.8, n=4 p<0.001). MI responded with
reversible increases in [Ca2+]i at 20mM glucose upon exposure to SA or SP (basal to
peak difference, SA: 0.069±0.025 n=10, p<0.05 , SP: 0.033±0.015, n=12 p<0.05).
Our data provide evidence for stimulatory roles of SA and SP, possibly acting via the
Gq-coupled FFA2, and they implicate this ScFA receptor in the management of
glucose homeostasis.
WCIDT-0093
Role of gut microbiota in metabolism and in the pathophysiology of obesity
and diabetes

AN ADIPOSE TISSUE 16S RIBOSOMAL DNA TARGETED METAGENOMIC


CATALOGUE OF PATIENTS WITH METABOLIC DISEASE
B. Coupé1, S. Paissé1, B. Lelouvier1, F. Servant1, A.C. Brunet1, J. Christensen2,
C. Schuster-Klein3, B. Guardiola-Lemaitre3, F. Pattou4, J. Amar5, M. Courtney1,
R. Burcelin6
1
Vaiomer, Molecular and Cell Biology, Labège, France
2
Vaiomer- Molecular and Cell Biology,
Institut des Maladies Métaboliques et Cardiovasculaires- INSERM U1048, Labège,
France
3
Servier, ADIR- Groupe de Recherches Servier, Suresnes, France
4
European Genomic Institute for Diabetes- INSERM UMR 1190,
Centre Hospitalier Régional Universitaire- Université de Lille, Lille, France
5
Hôpital Rangueil- Département Thérapeutique- Université Paul Sabatier-,
Institut des Maladies Métaboliques et Cardiovasculaires- INSERM U1048, Toulouse,
France
6
Institut des Maladies Métaboliques et Cardiovasculaires- INSERM U1048,
Université Paul Sabatier, Toulouse, France.

Background: Metabolic disease is characterized by dysbiosis of gut microbiota


which can translocate from the intestine to adipose tissue and interact with
corresponding cells to control inflammation and their metabolic functions. To gain
knowledge we generated the first 16S rDNA metagenomics catalogue of human
omental adipose tissue.

Methods: 100 subjects in this study were enrolled from the ABOS cohort (A
Biological Atlas of Severe Obesity - ClinicalGov NCT01129297) of patients that some
were obese and eligible for bariatric surgery. Bacterial taxons were identified by
MiSeq Illumina based 16S rDNA targeted sequencing of V3-V4 region and quantified
by qPCR. Operational taxonomic units were generated with 97% identity and
taxonomically assigned.

Results: The 16S rDNA copy number per ng of total DNA in adipose tissue was
significantly higher in obese diabetic patients compared to non-diabetic (obese and
non-obese) patients. The analysis of significantly differential relative abundance of
16S rDNA sequences revealed that specific bacterial taxa correlate independently
with BMI, fasting glycemia and Hba1C. A specific signature of bacterial taxa could be
identified for obese/diabetic, obese/non-diabetic, and non-obese/non-diabetic
subjects.

Conclusions: We have generated the first human catalogue of the adipose tissue
microbiome and identified significant differences in abundance of bacterial taxa
dependent on clinical grouping of subjects. These findings highlight the potential for
differential host-microbe crosstalk from specific metagenomic signatures within a
tissue.
WCIDT-0150
Role of gut microbiota in metabolism and in the pathophysiology of obesity
and diabetes

GPCR LIGAND SECRETOME OF MOUSE DUODENUM: POSSIBLE TARGETS


FOR INVESTIGATIONS ON MECHANISMS OF ACTION OF
BARIATRIC/METABOLIC SURGERY
P.F. Pedro, A. Alami, R. Hawkes, S. Amisten, S.J. Persaud, F. Rubino, P.M. Jones
King's College London- Denmark Hill Campus, Metabolic and Bariatric Surgery-
Division of Diabetes and Nutritional Sciences- James Black Centre, London,
United Kingdom

Background: Peptide hormones secreted by enteroendocrine cells (incretins and/or


putative anti-incretins) have been implicated in the improved metabolic responses
induced by bariatric surgery. Incretins can influence insulin secretion via G-protein
coupled receptors (GPCRs). We have previously identified the expression of 293
GPCRs in islets. Here we investigate the expression of mRNA species for all known
peptide/protein ligands targeting islet GPCRs in mouse duodenum.

Methods: We hypothesised that incretin and/or anti-incretin expression will be


modified by food intake, so we analysed changes in mRNA expression in duodenum
from fed mice (n=6) and mice deprived of food for 24h (n=6). To identify novel
candidate incretins and/or anti-incretins we have used a non-biased qRT-PCR array.

Results: Our GPCR-ligand mRNAs screening identified the expression of 94 different


molecules in extracts from mouse duodenum, of which 66 were expressed at high
levels (Ct<26), 22 at medium levels (Ct 26-30) and 6 at low levels (Ct>30). We
detected mRNAs encoding known enteroendocrine peptides such as cholecystokinin,
preproglucagon, GIP, ghrelin and somatostatin but also detected high/medium levels
of a range of other biologically active molecules, including corticotropin-releasing
hormone, Arginine Vasopressin (AVP) and islet amyloid polypeptide (IAPP).
Starvation induced changes in mRNA expression of a number of these GPCR-ligands
including cholecystokinin, Gastric inhibitory polypeptide (GIP), ghrelin, AVP and
IAPP.

Conclusion: This study demonstrates that mouse duodenum expresses many more
biologically active peptides than the classical incretins, and that their expression
levels are modified by food intake. The availability of this mouse duodenal
“secretome” offers targets for future studies of the role(s) of enteroendocrine peptides
in responses to bariatric surgery.
WCIDT-0100
Role of the gastrointestinal tract in glucose metabolism

EFFICACY AND SAFETY OF SITAGLIPTIN IN SUBJECTS WITH 2 DIABETES


MELLITUS WITH FATTY LIVER
V. Kapetivadze, R. Tabukashvili, N. Gegeshidze, K. Tchaava, Z. Maglaperidze,
Z. Grigorashvili
Tbilisi State Medical University, Internal Medicine, Tbilisi, Georgia

Objective: The aim of this study was to investigate the efficacy and safety of
sitagliptin plus metformin in treatment type 2 diabetes mellitus patients with fatty
liver.

Methods: We evaluated 30 mean age 55,4+ 1,7 (16 females, 14 males) type 2
diabetes mellitus patients with fatty liver. The patients were administrated sitagliptin
(50 mg/body day) for 3 months. Sitagliptin plus metformin (1000 mg) was given in
combination with standard therapy (thiogamma, essencialee forte, Vit. E). The
patients were divided in to 2 groups. Control group (14 patients) were given standard
treatment. Experimental group (16 patients) were additionally given 50 mg sitagliptin
daily. We studied plasma glucose, serum HBA 1c, AST, ALT and j-G-TP levels were
observed before and after 3 months of treatment with sitagliptin.

Results: Three months after clinical observations in experimental group was


obtained more significant decrease of the plasma glucose, serum HBA 1c, AST, ALT
and j-G-TP levels.

Conclusion: This combination (sitagliptin plus metformin) may be an alternative


treatment option in type 2 diabetes mellitus patients with fatty liver.

Key Words: Sitagliptin, Metformin, Fatty liver.


WCIDT-0111
Role of the gastrointestinal tract in glucose metabolism

CHANGE OF INTESTINAL HORMONE AFTER LAPAROSCOPIC SLEEVE


GASTRECTOMY WITH DUODENAL JEJUNAL BYPASS FOR NON-MORBID
OBESE T2DM PATIENTS
K. Kasama1, Y. Seki1, A. Watanabe1, H. Haruta1, Y. Kurokawa2
1
Yotsuya Medical Cube, Weight loss and Metabolic Surgery Center, Chiyoda, Japan
2
Yotsuya Medical Cube, Director, Chiyoda, Japan

Background

Laparoscopic Sleeve gastrectomy with Duodenojejunal bypass (LSG/DJB) reveals


better outcome for morbid obese T2DM patients than Sleeve gastrectomy alone. We
also reported good outcome of LSD/DJB for low BMI (BMI<35) but hormonal change
after LSG/DJB are still unclear.

Methods

Sixty six low BMI patients (m: 37, f:29) with T2DM underwent LSG/DJB from 09/2007
to 12/2014. 37 of them were followed up at least 1 year after surgery

Average BMI, BW at the time of surgery was 31.7kg/m2, 88.4kg. Average HbA1C at
the first visit was 9.1%, average duration of DM was 8.7years and 89% of them had
used insulin before surgery. Change of parameters with meal tolerance test, including
Active GLP-1, insulin, C-peptide, GIP, Oxytomodulin, PYY, proinsuin, glucagon and
HOMA-R were checked pre and 3 months postoperatively

Results

Average BMI, BW, HbA1C at 1 year after surgery was23.7, 66.1kg, 6.3%. Remission
of T2DM was 56% and HbA1c<7% was 74%.

Pre and postope. AUC of active GLP-1, insulin, C-peptide, GIP, Oxytomodulin, PYY,
proinsuin, glucagon was pre:667/post:2302pM, 28.09/50.19, 2.42/4.07,
54403/53054, 0.27/1.97, 0.21/0.77, 23.28/27.29 18.65/23.60, respectively. HOMA-R
changes from 9.9+-6.8 to 2.3+-3.2 Active GLP-1, C-peptide,Oxytomodulin, PYY and
HOMA-R were significantly different between pre and postope .

Conclusions

LSG/DJB showed significant change of DM related factors and is thought to be an


effective treatment option for non-morbid obese T2DM patients.
WCIDT-0138
Role of the gastrointestinal tract in glucose metabolism

IMPAIRMENT OF INTESTINAL BARRIER INTEGRITY IN HUMAN OBESITY:


INVOLVEMENT OF DIETARY LIPIDS
L. Genser1, S. Benaissa2, A. Torcivia3, M. Rousset2, K. Clement4, E. Brot-Laroche2,
A. Leturque2, S. Thenet5, C. Poitou-Bernert6
1
Institute of Cardiometabolism and nutrition ICAN, UMR 1166 INSERM UPMC UPD-
Pitié-Salpêtrière Hospital- Paris- Department of digestive surgery-
liver transplantation- Pitié-Salpêtrière Hospital, Paris, France
2
Institute of Cardiometabolism and nutrition ICAN, UMR 1138 INSERM UPMC UPD-
Cordeliers Research Center- F-75006 Paris, Paris, France
3
Institute of Cardiometabolism and nutrition ICAN, Department of digestive surgery-
liver transplantation- Pitié-Salpêtrière Hospital, Paris, France
4
Institute of Cardiometabolism and Nutrition ICAN, UMR 1166 INSERM UPMC UPD-
Pitié-Salpêtrière Hospital- Paris- F-75013 France- Assistance Publique-
Hôpitaux de Paris- Pitié-Salpêtrière Hospital-
Heart and metabolism department Paris- F-75013 France, Paris, France
5
Institute of Cardiometabolism and Nutrition ICAN, UMR 1138 INSERM UPMC UPD-
Cordeliers Research Center- F-75006 Paris-
Cellular and Molecular pharmacology laboratory- Ecole Pratique des Hautes Etudes-
F-75006 Paris, Paris, France
6
Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris-
Pitié-Salpêtrière Hospital- Heart and metabolism department Paris- F-75013 France-
UMR 1166 INSERM UPMC UPD- Pitié-Salpêtrière Hospital- Paris- F-75013 France,
Paris, France

Background: Intestinal barrier alteration may contribute to the inflammation


associated to obesity and metabolic disorders. Documented in rodents, this feature is
not fully established in humans. Moreover, the underlying mechanisms remain to be
deciphered. We characterized intestinal barrier integrity in obese (Ob) patients and
type-2-diabetic obese patients (Obd) undergoing gastric bypass (GBP) surgery.

Methods: In-vivo, intestinal paracellular permeability (IPP) was estimated by


lactitol/manitol excretion ratio (L/M) in 31 Ob and 15 Obd patients. Fecal calprotectin
levels were measured by ELISA. Jejunum tissues from surgical waste of GBP (47 Ob,
29 ObD) and lean surgeries (n=14) were analyzed ex vivo for IPP assays in Ussing
chambers using FITC-labeled tracers of different sizes.

Results: Measured after an overnight fast, L/M values did not differ between Ob
(n=28) and Obd (n=17) subjects (1.2%±2.1 vs 2.1%±2; p=0.80) and revealed
unaltered in vivo IPP toward small molecules (0.4 kDa) as compared to the healthy
standard (3%). Fecal calprotectin levels were within normal ranges (<100μg/g),
indicating no intestinal microinflammation. In fasting condition, ex-vivo IPP toward 0.4
to 40 kDa tracers was similar in jejunum of Ob or Obd as compared to lean subjects.
However, lipid micelles mimicking a lipid-rich meal increased paracellular permeability
in cultured human enterocytes and in jejunum samples from obese subjects (p<0.05).

Conclusion: Human obesity is not accompanied by changes of in vivo and ex vivo


IPP in fasting conditions. However, dietary lipids may loosen directly the epithelial
barrier by mechanisms, yet unexplored, that we will analyze in the context of obesity.
WCIDT-0143
Safety of bariatric/metabolic surgery

THE MANAGEMENT OF POST-PRANDIAL HYPOGLYCAEMIA (PPH)-


INSIGHTS INTO THE ROLE OF GUT HORMONES IN BOTH THE PATHOLOGY
AND TREATMENT OF PPH
G. Tharakan1, P. Behary1, W. Al Najim1, A. Miras1, S. Purkayastha2, S. Hakky2,
K. Moorthy2, A. Ahmed2, H. Chahal3, T. Tan1
1
Imperial college London, 6th Floor- Commonwealth Building, London,
United Kingdom
2
Imperial college London, Department of Surgery and Cancer, London,
United Kingdom
3
Imperial college London, Imperial Weight Centre, London, United Kingdom

Bariatric surgery for obesity remains the most effective method to achieve weight loss
and improvements in mortality. However, as the number of procedures increases to
match the rising burden of obesity, unusual metabolic complications are now coming
to the fore. One example of this is postprandial hypoglycaemia (PPH).

The management of PPH remains clinically challenging. Currently there are no


consensus guidelines on the treatment of PPH, but there are case reports and series
describing treatments ranging from dietary changes to surgery. However, the
mechanism of these treatments as well as the pathogenesis of PPH remains elusive.

We present our experience of managing these patients at a tertiary centre. Our


cohort has been comprehensively investigated via a series of tests; continuous
glucose monitoring, prolonged oral glucose tolerance test and mixed meal tests. We
provide results of these investigations in our cohort and highlight the advantages and
limitations of each test. Furthermore we present the gut hormone response in our
PPH patients and an asymptomatic group. Our data (Figure 1) implicates glucagon
dysregulation in the pathology of PPH.

In addition we describe the successful management of PPH using a GLP-1 agonist,


Liraglutide- a novel treatment previously only described in 5 other patients. We
demonstrate the effects of GLP-1 agonists on glucose variability in PPH patients and
suggest that its suppressive effect on glucagon may account for its benefits in this
condition.
WCIDT-0146
Safety of bariatric/metabolic surgery

IS IT SAFE TO PERFORM BARIATRIC SURGERY IN OBESE PATIENTS WITH


CHRONIC KIDNEY DISEASE?
D. Elfadl, S. Ramar, H. MacLaughlin, I. Macdougall, A. Patel, F. Rubino, A. Chang
King's College Hospital, Minimally Invasive Surgery, London, United Kingdom

Introduction:

Obese patients with chronic kidney disease (CKD) constitute a high risk group
requiring multidisciplinary management. Weight loss has life-changing benefits such
as resolution of diabetes and eligibility for transplantation. A protocol has been
introduced at King’s College Hospital (KCH) which defines multidisciplinary team
working to improve perioperative safety and efficacy. Early results are presented
here.

Aim:

To determine 30-day morbidity and mortality, and assess safety & early benefits.

Methods:

A retrospective analysis of prospectively maintained data.

Results:

Between April-2013 and March-2015, eleven patients with CKD stages II-V and mean
age of 47.6 underwent bariatric surgery at KCH. The average BMI was 45.6. Ten
patients underwent laparoscopic sleeve gastrectomy, while one patient had
laparoscopic revision of a sleeve gastrectomy. The median length of stay was 4 days
(4-16). 54.5% of patients were diabetic, and all but one were hypertensive. Six
patients had obstructive sleep apnoea. Ten were on haemodialysis.

One patient had a pulmonary embolism on day-1 postoperatively. One patient had
abdominal pain 3-weeks post operatively which required hospital admission. There
was no mortality.

At 6 months, the percentage of excess body weight lost was 13-119%. 5/10
hypertensive patients, and one diabetic patient no longer required medication. Nine
patients were on haemodialysis, while one patient underwent renal transplantation.

Conclusion:
Under the current protocol at KCH, we report morbidity of 18.1%, and no mortality at
30 days. These are early results. However, they indicate that we can safely perform
bariatric surgery on patients with CKD on dialysis and achieve good outcomes.

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