1. Screening and Follow-up in Obese subjects Bariatric Sugery: When? Gabriella Garruti Department of Emergency and Organ Transplantation Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases (Chairman: prof. F. Giorgino) Et lucem sed aliam reddit… Bari 27 novembre 2009

2. Bari 27 novembre 2009 Et lucem sed aliam reddit…

3. What is Overweight?

4. Underweight<18.5 Kg/m 2 Normal-weight18.5 - 24.9 Kg/m 2 Overweight25.0 – 29.9 Kg/m 2 Obesity category 1st30.0 – 34.9 Kg/m 2 2nd35.0 – 39.9 Kg/m 2 3rd> 40.0 Kg/m 2 BMI Overweight and Obesity: When? WAIST FAT distribution Central obesity 94 Man:> 94 (102) cm 80 Woman: > 80 (88) cm IDF /(ATPIII)

5. Diet Physical Activity Lifestyle Modification Pharmacotherapy Surgery Obesity Treatment Pyramid Et lucem sed aliam reddit… Bari 27 novembre 2009

6. Guidelines for Selecting Obesity Treatment Treatment25-26.927-29.930-34.935-39.9>40 Diet, Exercise, Behavior Tx +++++ Pharmaco- therapy With co- morbidities +++ Surgery With co- morbidities + The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000, NIH Pub. No.00-4084 modified by Garruti 2008 + BMI Category (kg/m 2 ) Bari 27 novembre 2009

7. 13.02.05 Gastric Bypass (Roux-en-Y) Only when Lifestyle is unhealthy Gastric banding Bariatric surgery Et lucem sed aliam reddit… Bari 27 novembre 2009

8.  The operations employed for morbid obesity are not to be confused with plastic surgery  Real risk comes with each surgical procedure  Prospective patients should also be thoroughly convinced that they have exhausted all other reasonable avenues of weight loss before selecting surgery  The operations employed for morbid obesity are not to be confused with plastic surgery  Real risk comes with each surgical procedure  Prospective patients should also be thoroughly convinced that they have exhausted all other reasonable avenues of weight loss before selecting surgery Bariatric surgery: what is? Et lucem sed aliam reddit… Bari 27 novembre 2009

9. Indications 1.BMI >40 kg/m 2 or BMI 35–39.9 kg/m 2 and life-threatening cardiopulmonary disease, severe DIABETES, or lifestyle impairment 2.Failure to achieve WL with Medical Treatment Controintraindications 1.History of noncompliance with medical care 2.Psychiatric illnesses: personality disorder, uncontrolled depression, suicidal ideation, substance abuse 3.elevated ASA risk NIH Consensus Development Panel. Ann Intern Med 1991;115:956. Bariatric Surgery: When ? EAES /ASBS 2005 BMI 30-35 kg/m2 & life-threatening comorbidities Sauerland et al. Surg Endosc 19:200 Buchwald et al. J Am Coll Surg 200:593 Et lucem sed aliam reddit… Bari 27 novembre 2009

10.  Obesità di durata superiore a 5 anni  BMI > 40Kg/m 2 o BMI >35Kg/m 2 con comorbidità*  Età: da 18-65 anni  Fallimento Tx medica (dietetica, farmacologica, comportamentale) per almeno 1 anno  Assenza di cause endocrine di obesità  Rischio anestesiologico max < ASA 2  Assenza di malattie psichiatriche e/o disturbi del comportamento alimentare (DCA).  Compliance del paziente (follow-up) NIH 1998- LIGIO 1999 EAES /ASBS 2005 Et lucem sed aliam reddit… Indicazioni Bari 27 novembre 2009

11. BMI >35 con comorbilità*  OSAS/Pickwick  Ipertensione arteriosa  Scompenso cardiaco  Diabete mellito tipo 2  Osteoartrosi  Colelitiasi  Dislipidemie  Insuff. venosa cronica arti inferiori  Impotenza/Irregolarità mestruali /Infertilità  Iperuricemia  Irsutismo  Nefrolitiasi Indicazioni Et lucem sed aliam reddit… Bari 27 novembre 2009

12. Et lucem sed aliam reddit… Bariatric Sugery: how important is the multidisciplinary approach? Bari 27 novembre 2009

13. Et lucem sed aliam reddit… Bariatric Sugery: how important is the multidisciplinary approach? Anesthesiologist, Cardiologist, Dietitian or Nutritionist, Endocrinologist, Pneumologist, Psychiatrist, Surgeon Bari 27 novembre 2009

14. Valutazione clinica e strumentale prima della chirurgia  Esami ematochimici  Inquadramento endocrino-metabolico * e genetico  Rx torace  Ecografia addome superiore e inferiore  Doppler venoso arti inferiori  Emogasanalisi, spirometria, polisonnografia  Inquadramento psicologico-nutrizionale (psichiatra e dietisti)  Rx baritato (+Trendelenburg per ernia iatale)  EGDS + biopsia per infezione H. pylori  Consulenza cardio-anestesiologica Et lucem sed aliam reddit… Bari 27 novembre 2009

15. Inquadramento endocrino- metabolico e nutrizionale Indagine alimentare, variabili antropometriche Indagine alimentare, variabili antropometriche Indici nutrizionali Indici nutrizionali HOMA/ OGTT per glicemia e insulinemia HOMA/ OGTT per glicemia e insulinemia Pattern ormonali: Pattern ormonali: –asse ipofisi-surrene/gonadi –asse ipofisi-tiroide –asse GH /IGF1 Ecografia tiroidea Ecografia tiroidea Mineralometria ossea computerizzata “Total body” Mineralometria ossea computerizzata “Total body” Et lucem sed aliam reddit… Bari 27 novembre 2009

16. Palatableness (taste receptors) Geography Nutrients availability Economic situation Culture Religion Is Diet dependent on …? Energy needs Environment Genes (metabolism) Your Gut Has Taste Receptors ScienceDaily (Aug. 21, 2007) Et lucem sed aliam reddit… Bari 27 novembre 2009

17. Lazar Science 2005 modified by Garruti In the Pima, survival mechanisms evolved to store fat extremely efficiently (“thrifty genotype”) This GENETIC MAKE-UP would have served the tribe well in the harsh desert climes of the southwest Today this so-called "thrifty gene" means 70% of the Arizona Pima are obese and diabetics The Desert’s perfect foods Et lucem sed aliam reddit… Normalweight Overweight Obese Bari 27 novembre 2009

18. Bari 27 novembre 2009 Et lucem sed aliam reddit…

19. Indagine alimentare Et lucem sed aliam reddit… 2200 6299.2154 41.8 20 12% 28% 60% 3 X XX pane, pasta, condimenti, rustici verdura Dieta a b.i.g 1200 Kcal/Die Attività fisica (v. piramide attività fisica) Bari 27 novembre 2009 Giovanna Mallardi

20. Diet & Energy needs Neuronal circuits in the hypothalamus affect Satiation (level of fullness during a meal which regulates the amount of food consumed) Satiety (level of hunger after a meal is consumed which regulates the frequency of eating) Schwartz et al. 2000 Nature Et lucem sed aliam reddit… Bari 27 novembre 2009

21. Energy density: Volume versus calories All foods have a certain number of calories within a given amount (volume) Foods with high energy density have a large number of calories in a small volume Alternatively foods with low energy density provide a larger portion size with a fewer number of calories. Et lucem sed aliam reddit… Bari 27 novembre 2009

22. Energy Density of Selected Foods Energy Density (kcal/g) Lettuce Vegetable soup Skim milk Apple Black beans White fish Yogurt Vegetable lasagna Roast chicken White bread Pretzels Cheddar cheese Salad dressing Potato chips Bacon Butter Klein S, et al. Gastroenterology. 2002 Et lucem sed aliam reddit… Bari 27 novembre 2009

23. HEALTHY PYRAMID FOOD (Harvard Medical School) Bari 27 novembre 2009

24. Classification Gastric restriction Primarily restrictive and partially malabsorptive Primarily malabsorptive and partially restrictive Procedure  Adjustable Gastric Banding  Roux-en-Y Gastric Bypass  Sleeve Gastrectomy  Biliopancreatic diversion with duodenal switch  Biliopancreatic diversion  Distal gastric bypass Current Bariatric Surgical Procedures Et lucem sed aliam reddit… Bari 27 novembre 2009

25. Restrictive Gastric Surgery Vertical gastroplasty Adjustable gastric banding Intragastric balloon (BIB) Et lucem sed aliam reddit… Bari 27 novembre 2009

26. Laparoscopic Adjustable Gastric Banding Silicone band placed around upper stomach to create a small pouch. Outlet diameter can be changed by infusing or withdrawing saline from port. Gastric Band Connection tubing Access port (reservoir) American Society for Metabolic and Bariatric Surgery, www.asbs.org LapBand TM Puglisi 2008 Et lucem sed aliam reddit… Bari 27 novembre 2009

27. Roux-en-Y gastric bypass Et lucem sed aliam reddit… Bari 27 novembre 2009

28.  Sleeve gastrectomy with rerouting of small intestine through “nutrient limb” and “biliopancreatic limb”  Digestion and absorption are limited to 100 cm “common channel” of terminal ileum  Causes marked weight loss, but can lead to significant nutritional deficiencies Biliopancreatic Diversion with Duodenal Switch Marceau P. et al. World J Surg 1998;22:947-54 Et lucem sed aliam reddit… Bari 27 novembre 2009

29. Follow-up (post- LAGB and post- GBP) 0 1 3 6 9 12 15 18 21 24 months EGDS Calibration Rx ? Cardiologist, Dietitian or Nutritionist, Endocrinologist, Pneumologist, Psychiatrist surgeon ……? Et lucem sed aliam reddit… Bari 27 novembre 2009

30. Energy Metabolism in mammals Basal Metabolic Rate [Obbligatory Thermogenesis (Th)] Exercise-induced Th Diet-induced Th Major effects of Bariatric Surgery Weight Et lucem sed aliam reddit… Bari 27 novembre 2009

31. Bari 27 novembre 2009 Et lucem sed aliam reddit…

32. Indagine alimentare Et lucem sed aliam reddit… 1000 99.2154 41.8 30 15% 28% 57% 3 X XX ? Dieta a b.i.g 1000-1200 Kcal/Die Attività fisica (v. piramide attività fisica) Bari 27 novembre 2009 Maria A. Lucafo’ & Giovanna Mallardi X X

33. Bari 27 novembre 2009 Et lucem sed aliam reddit…

34. Suggested Energy Deficit based on Initial BMI Initial BMI (Kg/m 2 ) Suggested Energy Intake (kcal/d) Approximate Initial Energy Deficit (kcal/d) 25-29.9?500 30-34.9?500 35-39.9?500-1000 >40 ?500-1000 >50 ?? National Institutes of Health, National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults – The Evidence Report. Obes Res. 1998;6(suppl 2):51S-209S Bari 27 novembre 2009 Et lucem sed aliam reddit…

35. Obrien et al. Ann Intern Med. 2006 Weight Loss, % Baseline Surgical (LapBand) Nonsurgical *VLCD, behavioral modification, and pharmacotherapy 6 mo12 mo18 mo24 mo Weight Loss after Bariatric Surgery or Medical Therapy* BMI between 30 and 35 Kg/m 2 Et lucem sed aliam reddit… Bari 27 novembre 2009

36. MesiWL(Kg)/SEMWE(Kg)/SEM%EWL/SEM 1° mese9.5/1.146.5/7.420.2/4.2 2° mese14.4/2.548.5/7.223.6/3.8 3° mese13.6/2.545.1/6.624.6/5.0 Parametri antropometrici dopo BIB 6° mese18.0/8.040.0/5.627.0/7.8 Et lucem sed aliam reddit… Bari 27 novembre 2009

37. Parametri antropometrici dopo LapGB Mesi WL(Kg)/SE M WE(Kg)/SE M %EWL/SEM 1° mese6.0/1.046.0/7.713.0/2.3 3° mese9.7/2.140.5/6.419.8/3.8 4° mese9.3/3.739.6/5.319.7/3.3 8° mese13.1/1.337.1/3.528.3/3.2 12° mese11.8/2.338.8/3.7626.2/5.4 18° mese23.1/6.532.5/3.830.0/5.3 Et lucem sed aliam reddit… Bari 27 novembre 2009

38. % of subjects with low or high compliance Excess Weight (EWL) and Compliance to Comprehensive Medical Therapy* after Gastric Banding Excess Weight Loss (EWL) and Compliance to Comprehensive Medical Therapy* after Gastric Banding low high low high Lucafo’ MA, Rotelli MT, De Tullio A. 2008 unpublished *[life-style modifications (diet, exercise) + pharmacotherapy] %EWL in subjects with low or high compliance Et lucem sed aliam reddit… Bari 27 novembre 2009

39. ProcedureApproximate Loss of Excess Weight (%) Laparoscopic gastric banding 45–65 Gastric bypass procedure 55–65 Biliopancreatic diversion (DS) 60–75 Effect of Different Bariatric Surgical Procedures on Weight Loss Klein et al. Gastroenterology. 2002;123:882-932 Et lucem sed aliam reddit… Bari 27 novembre 2009

40. Comorbidity outcomes after Bariatric surgery Comorbidity Improved/Resolved Diabetes100% Coronary artery disease100% Hypercolesterolemia96% Gastroesophageal reflux d.96% Sleep apnea93% Hypertension88% Osteoarthritis88% Hypertriglyceridemia86% Depression 55% Adapted from Schauer et al. Ann Surg 2000 Busetto et al. Obes Surg 2000 10: 569 Pontiroli et al JCEM 2002 87:3555 Scopinaro et al. Diabetes Care 2005; 28:2406 Busetto et al. NMCD 2008; 18:112 Et lucem sed aliam reddit… Bari 27 novembre 2009

41. THE EFFECTS OF GASTRIC BANDING ON RED BLOOD CELL AGGREGATION & DEFORMABILITY IN MORBIDLY OBESE SUBJECTS Puglisi Francesco, Capuano Palma, Giorgio Catalano, Garruti Gabriella, Trerotoli Paolo, Tedeschi Michele, De Fazio Michele, Cicco Giuseppe, Giorgino Francesco, Memeo Vincenzo TotalMF N209 (45%)11 (55%) Mean age (SD)40.8 (12.2)36.4 (11.3)44.4 (12.3) Range22-6022-5123-60 Mean Baseline weight (SD)132.3 (23.4)142.4 (26.9)124 (17.3) Range100-195112-195100-161 Mean Baseline BMI (SD)45.8 (5.9)45.6 (6.5)45.9 (5.8) Range37.4-58.637.4-55.738.9-58.6 Arterial hypertension9 (45%)3 (33.3%)6 (54.5%) Hypertryglyceridemia8 (40%)5 (55.6%)3 (27.3%) Smoke7 (35%)3 (33.3%)4 (36.4%) Diabetes7 (35%)3 (33.3%)4 (36.4%) Vascular dis.5 (25%)2 (22.2%)3 (27.3%) Joint diseases4 (20%)1 (11.1%)3 (27.3%) Hypoventilation syndrome3 (15%)1 (11.1%)2 (18.2%) Heart diseases.3 (15%)2 (22.2%)1 (9.1%) Anxiety-depression3 (15%)0 (0%)3 (27.3%) Thyroid dysfunction2 (10%)0 (0%)2 (18.2%) Gallbladder stones1 (5%)0 (0%)1 (9.1%) Box plot comparing EI 3 PA at baseline and 3 and 6 months after surgery. Bari 27 novembre 2009 Et lucem sed aliam reddit… AI: aggregation index; EI: elongation index

42. T0T3T6 p-values T3 vs T0T6 vs T0 AI %0.74 (0.04)0.72 (0.05)0.67 (0.06)0.0130.000 AI t1/21.34 (0.36)1.38 (0.3)1.49 (0.29)0.34470.189 EI 0.03 Pa0.042 (0.016)0.039 (0.016)0.043 (0.023)0.320.757 EI 3 Pa0.379 (0.065)0.412 (0.056)0.449 (0.067)0.0490.0001 EI 30 Pa0.584 (0.128)0.646 (0.043)0.669 (0.064)0.110.0274 Weight 132.305 (23.446) 117.85 (25.775) 109.75 (25.007)0.0001 BMI45.813 (5.977)40.813 (6.867)37.965 (6.792)0.0001 Tot Chol207.8 (23.305)196.6 (16.529) 185.15 (18.883)0.00450.0001 HDL Chol48.25 (11.201)50.15 (10.277)53.5 (8.918)0.1970.0048 LDL Chol132.05 (21.197) 128.21 (26.388)122.2 (23.294)0.0860.0042 Tryglicerides154.75 (51.759) 138.85 (38.232)129.7 (37.542)0.01610.0038 Glycaemia103.7 (15.058)99.65 (10.937)97.65 (7.436)0.160.38 Insulin33.66 (17.155) 27.171 (13.507)24.29 (12.446)0.0010.0001 AI: aggregation index; EI: elongation index THE EFFECTS OF GASTRIC BANDING ON RED BLOOD CELL AGGREGATION & DEFORMABILITY IN MORBID OBESE PATIENTS Puglisi Francesco et al. Box plot comparing AI% 3 at baseline and 3 and 6 months after surgery Et lucem sed aliam reddit… Bs 3M6M Bari 27 novembre 2009

43. BMI DISTRIBUTION IN A COHORT OF TYPE 2 DIABETIC SUBJECTS Bari 27 novembre 2009 Et lucem sed aliam reddit… GARRUTI G., VITA MG, GIAMPETRUZZI F et al. 2008 unpublished

44. LapGB LIMITI  Anestesia (vs Tx medica integrata)  Limitato calo ponderale (vs Tx chirurgica malassorbitiva)  Obbligatorio “counseling”  Alimentazione semiliquida per ~ 1 settimana (600 - 800Kcal/die) (vs Terapia medica ed chirurgica malassorbitiva)  Durata del pasto:> 40 min  Intervallo tra cena e bed-time: 2 h VANTAGGI  Dieta ipocalorica bilanciata (proteine 19,4%; glucidi 56,2% ; lipidi 24,4%) + integratori  Graduali modificazioni dell’immagine corporea Et lucem sed aliam reddit… Bari 27 novembre 2009

45. Complications after Gastric Bypass The bypassed portion of intestine is where the majority of calcium and iron absorption takes place LONG-TERM COMPLICATIONS anemia osteoporosis Other clinically important deficiencies Vitamin B 1 (thiamine) Vitamin B 12 lack of gastric intrinsic factor (GIF) Lifelong follow-up with a daily multi-vitamins and mineral supplementation are strongly recommended to prevent nutritional complications Et lucem sed aliam reddit… Bari 27 novembre 2009

46. GBP & Dumping syndrome  Gastric bypass operations may also cause "dumping syndrome" food or liquids travel too rapidly through the small intestine (sweets are often the culprit)  Dumping symptoms include nausea weakness sweating faintness diarrhea  Symptoms dissipate after the patient rests??? Et lucem sed aliam reddit… Bari 27 novembre 2009

47. Brain NPY AGRP galanin Orexin-A dynorphin Stimulate α-MSH CRH/UCN GLP-I CART NE 5-HT Inibit Central Signals Glucose CCK, GLP-1 Apo-A-IV Vagal afferents Insulin Ghrelin Leptin Cortisol Peripheral signals Peripheral organs +   + Gastrointestinal tract Adipose tissue Food Intake Adrenal glands External factors Emotions Food characteristics Lifestyle behaviors Environmental cues Regulation of Food Intake Schwartz et al. 2000 Nature Bari 27 novembre 2009 Et lucem sed aliam reddit…

48. Et lucem sed aliam reddit… Bari 27 novembre 2009

49. ANP Bari 27 novembre 2009 Et lucem sed aliam reddit… Adipose Tissue depots are a marvelous source of adipocyte precursors stem cells

50. Any surgical procedure  normalizes hyperglycemia  restores insulin sensitivity  prevents progression from IGT to DM  reduces mortality from DM Gastric bypass and Biliopancreatic diversion  restores euglycemia and normal insulin long before any significant weight loss Changes in hormones secretion from the GI tract Bariatric surgery and Glycaemia Et lucem sed aliam reddit… Bari 27 novembre 2009

51. Bariatric Surgery in DM2: When? “Should surgeons treat diabetes in severely obese people ?” J.H. Pinkney, Sjöström C.D., Gale E.A.M. Lancet 2001 357: 1357. Et lucem sed aliam reddit… Bari 27 novembre 2009

53. Rubino et al 2004 Ann Surg 240(2): 236–242 Incretins and anti-incretins in DM2 Et lucem sed aliam reddit…

54. Rubino et al. Ann Surg. 2004; 240(2): 236–242 Incretins and anti-incretins in DM2 after GBP Et lucem sed aliam reddit…

55.  [A] Simple gastro- jejunostomy Enhanced delivery of nutrients to the hindgut without excluding nutrient flow through the proximal intestine No improvement of Diabetes in diabetic GK animals. [B] DJB creates similar shortcuts of nutrients as in gastro- jejunostomy - includes the exclusion of the proximal intestine from the flow of nutrients - improves glucose tolerance and fasting glycemia in diabetic GK rats Exclusion of the duodenum is critical for the effect on diabetes Duodeno-jejunal bypass (DJB) and Diabetes Rubino et al. Diab. Care 2008 Et lucem sed aliam reddit…

56. Swiss pharmaceutical firm, Novartis, demonstrated in clinical studies that its investigational drug vildagliptin improves the function of pancreatic islets in both animals and humans. Vildagliptin, a novel investigational Incretin Enhancer, previously known as LAF237, inhibits DPP-4, resulting in an increase of circulating levels of GLP- 1, a crucial incretin hormone. Gastric inhibitory polypeptide (GIP), also known as the glucose- dependent insulinotropic peptide Drucker, D. J. J. Clin. Invest. 2007;117:24-32 Dipeptidyl peptidase IV (DPP4) enzyme that breaks down gut peptides especially GLP-1GLP-1 DPP-4 Inhibitors or Incretin Enhancers Et lucem sed aliam reddit…

57. Different effect of GBP on GIP in diabetic and nondiabetic patients Rubino et al. Ann Surg. 2004; 240(2): 236–242 Et lucem sed aliam reddit…

58. B ariatric Surgery in DM2 & MbS: When? Indications BMI >40 kg/m 2 or BMI 35–39.9 kg/m 2 and life-threatening cardiopulmonary diseases severe DIABETES EAES /ASBS 2005 BMI 30-35 kg/m2 & life-threatening comorbidities Sauerland et al. Surg Endosc 19:200 Buchwald et al. J Am Coll Surg 200:593 Systematic comparative studies with new therapeutic compounds - CB1 antagonists - CCK enhancers - DPP4 inhibitors - Incretin enhancers - Glitazones

59. Surgery V. MEMEO F. PUGLISI P. CAPUANO M. TEDESCHI M. A. LUCAFO’ Psychiatry L. ZAVOIANNI Internal Medicine & Endocrinology F. GIORGINO G.MALLARDI A. BELLOMO DAMATO F. BRESCIA G.STEFANELLI G. MALLARDI A. DE TULLIO Clinical Nurtition G. DE PERGOLA L. MANDOI A. RAFFO Anesthesia P. CARAVETTA Acknowledgements Endoscopy O. CAPUTI IAMBRENGHI Laboratory of D.E.T.O. M. T. ROTELLI Cardiology A. VENEZIANI Et lucem sed aliam reddit… Internal Medicine R. GIORGINO Bari 27 novembre 2009 Pneumology N. PALUMBO O. RESTA