Physiologic effects of metabolic surgery Y. Van Nieuwenhove , Piet Pattyn Department of Gastrointestinal Surgery UZ Gent Vanavond leren we dat GLP-1 postprandiaal door intestinale L-cellen wordt afgescheiden en een potent incretine is terwijl Ghreline tijdens vasten vrijkomt in de oxyntische maagmucosa, en het eerst gekende perifere orexigene hormoon is. Indien dit u niet kan boeien, vertel ik u ook erbij wat de rol is van het Gila monster in de behandeling van diabetes mellitus type2.

Weight loss surgery Kremen 1955 Malabsorption Mason 1965 Restriction

Metabolic effect? Gastric banding Gastric bypass Sleeve gastrectomy

Meer vrouwen?

Only weight loss? Buchwald (JAMA, 2004) Pories (Ann Surg, 1995)

Diabetes epidemic Zimmet, Nature 2001

Gut hormones GI tract is the biggest endocrinologic organ Secretion Motility Growth Satiety/hunger Energy balance Glucose and fat metabolism

Anorexigenous Orexigenous Systemic Central Central Systemic CCK PYY (Y2)(fysiol.) PP (Y4) GLP-1 OXM Amylin Leptin Central PYY (ARC!!) PP Orexigenous Central PYY (Y1 en Y5) Ghrelin AgRP Systemic

Leptin Adiposity hormone Found in “mutant” mice Leptin is “lipostatic” (long term) Proportional with body fat High concentrations in obesity resulting in insensitivity No immediate therapeutic use

Ghrelin 80% secreted by P/D1 cells in stomach Hunger hormone (Rindi, Histochem Cell Biol 2002) 80% secreted by P/D1 cells in stomach Hunger hormone Fat storage increases Therapeutic role In hyponutrition Obesitas => Vaccinatie tegen Ghrelin Gastrectomie

GLP-1 Secreted by L-cells in distal bowel Potent incretin Increases insuline secretion Decreases glucagon secretion Increases beta cell mass Slows gastric emptying and induces satiety Half-life only 2 minutes Degraded by DDP-4

Therapeutic use of GLP-1 Exenatide GLP-1 agonist Poison of Gila Monster (Heloderma suspectum) Byetta® Pancreatitis! Liraglutide (Victoza®) Sitagliptine DPP-4 inhibitor Potentializes GLP-1 en GIP Januvia®

Sleeve gastrectomy Reduction of 80% of Ghrelin production Decreases hunger sensation

Hindgut en foregut hypothese (F. Rubino, Ann Surg 2006) Hindgut hypothes R-Y gastric bypass, Scopinaro Food reaches distal bowel earlier early secretion of incretins GLP-1 GIP OXM Foregut hypothes Gastro-duodeno-jejunal exclusion Less anti-incretines?

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Adult nesidioblastose (noninsulinoma pancreatogenous hypoglycemic syndrome) Persistant hyperinsulinemic hypoglycemia Clear link with R-Y gastric bypass GLP-1 effect?

Long term outcome after laparoscopic adjustable gastric banding Y. Van Nieuwenhove, A. Stockman, E. Snoeck, H. Van Ommeslaeghe, K. Van Renterghem, D. Van de Putte, W.Ceelen, P. Pattyn Dept. Of Gastrointestinal Surgery University Hospital Ghent

Background First LAGB in Belgium in 1994 >50% were LAGB Peak of >10.000 interventions in 2004 Since 2006 => LAGB=LRYGB

Long term results? SOS-study

Patients and methods A retrospective study of a prospective database* Telephone interview - preliminary results consecutive patients who underwent SAGB at least 4 years earlier. Primary outcome was presence of the banding device at the time of analysis final excess weight loss maximal weight loss conversions to other procedures (*Ceelen et al. Ann Surg 2003)

Results 1085 patients had been called on march 26th 2009 4 (0,36%) patients had died 10 (1%) refused to cooperate 46 (4%) lost from follow-up 664 (61%) unreachable 361 (33%) responders Mean age was 36 years 77% were women mean initial BMI was 41,18 ± 6,20kg/m2 The median follow-up was 90 months (range 48-152)

Presence of the banding Removal of the band was carried out in 83 (24%) patients after a median interval of 61 months (range 6-125).

Weight loss Weight kg BMI kg/m2 BMI dropped to 30,10 ± 5,44kg/m2 after a mean of 43 ± 33 months Weight regain to 33,64 ± 6,74 kg/m2 at the time of analysis Overall 40 ± 31% excess weight loss and 28% of BMI Weight kg BMI kg/m2

Late complications Food impaction 11 3% Pouch dilatation 36 10% Band leakage 7 2% Port problem 10 2,3% Erosion 16 4,5% Oesophagitis 8 Oesophageal dilat. 5 1,3% Total 93 25%

Reinterventions 280 interventions in 123 patients (34%)

Conclusion These preliminary data show that after a follow-up between 4 and 12 years High intervention rate High system related problems Minor complications more than 3 out of 4 devices are still functioning, 1 out of 3 successfull 40% excess weight loss

Conclusion Not only weight loss as objective Comorbidities can cure after surgery Obese diabetici Clear metabolic effect GLP-1 Ghrelin Other types of surgery? For non-obese diabetics?

Duodenal-jejunal Bypass Sleeve EndoBarrier TM Gastrointestinal Liner Endo- and fluoroscopy Gersin et al, Surgical Innovation December 2007