type 2 diabetes is a surgical disease

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1 M. Lannoo, MD, University Hospitals Leuven Walter Pories claimed in 1992 type 2 diabetes is a surgical disease Buchwald et al. conducted a large meta-analysis THE FIRST OBSERVATIONS W. Pories 500 patients Long term sufficient weight loss Adequate follow up 163 studies 22,094 patients Surgical procedures Gastric Banding Gastric Bypass (Roux en Y) Gastroplasty Bilio-pancreatic Diversion Assesment of comorbities Diabetes Hypertension Hypercholesterolemia Obstructive Sleep Apnea N Engl J Med Aug 23;357(8): ) 1

2 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Resolution or improvement (% of patients) Diabetes AHT Hyperchol OSAS Buchwald et al. conducted a large meta-analysis (Buchwald H, Avidor Y,Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta analysis. Jama Oct 13;292(14): ) For all surgical procedures combined type 2 diabetes Resolved in 76.8% Resolved or improved in 86% of patients Complete remission by type of surgery 48% after gastric banding (operative mortality 0.1%) 84% after Roux en Y (operative mortality 0.5%) >95% after bilio-pancreatic diversion (operative mortality 1.1%) Remission of diabetes after gastric banding occurs over several weeks or month, whereas after gastric bypass it can occur within days OBSERVATIONS: mortality Sjöström et al. The Swedisch Obesity Study (SOS trial) Prospective, controlled Swedish Obese Subjects study. Effect= mainly 2010 underwent bariatric CVD surgery of DM pat (surgery group) 2037 received conventional treatment (matched control group). But not randomized, treatment of the control group not well defined, more pre-baseline cardiovascular events in controls The Swedisch Obesity Study (SOS trial) N Engl J Med Aug 23;357(8): ) Sjostrom L et al. n engl j med; 351;26, 2004 OBSERVATIONS: mortality OBSERVATIONS:sleeve gastrectomy Adams et al. N Engl J Med 357;8 august

3 OBSERVATIONS:sleeve gastrectomy author N %EWL 1y IDDM 2 AHT Sleep apnoea OBSERVATIONS:sleeve gastrectomy R DURATION OF DIABETES IS IMPORTANT Moon Han % 93% 100% Cottam % 75% 80% Sillechia 41 77% 63% 56,2% Vidal % Kasalicky % 65% Rosenthal et al Surg Obes Relat Dis 2009 Epub corrected proof REMARKABLE ANALOGY WITH RYGBP Tagaya 30 67% 56% Akkary Obes Surg : Ingestion of food GI tract Adapted from Brubaker PL, Drucker DJ Endocrinology 2004;145: ; Zander M et al Lancet 2002;359: ; Ahrén B Curr Diab Rep 2003;3: ; Buse JB et al. In Williams Textbook of Endocrinology. 10th ed. Philadelphia, Saunders, 2003: MECHANISMS: entero-insular axis Release of incretin gut hormones Active GLP-1 and GIP Pancreas Beta cells Alpha cells Glucose dependent Insulin from beta cells (GLP-1 and GIP) Glucagon from alpha cells (GLP-1) Glucose dependent Insulin increases peripheral glucose uptake Increased insulin and decreased glucagon reduce hepatic glucose output Blood glucose control MECHANISMS: entero-insulinar axis and type 2 DM? Insulin deficiency Islet MECHANISMS: entero-insulinar axis and surgery Excess glucagon Pancreas Alpha cell produces excess glucagon Diminished insulin Beta cell produces less insulin Hypothesis of the proximal bowel Diminished insulin Hyperglycemia Muscle and fat Liver Excess glucose output Insulin resistance (decreased glucose uptake) Adapted from Buse JB et al. In Williams Textbook of Endocrinology. 10th ed. Philadelphia, Saunders, 2003: ; Hypothesis of the distal bowel Buchanan TA Clin Ther 2003;25(suppl B):B32 B46; Powers AC. In: Harrison s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill, 2005: ; Rhodes CJ Science 2005;307:

4 MECHANISMS: entero-insulinar axis and surgery Surgical procedures Physiology: entero-insular axis Hypothesis of the distal bowel: Expedited of nutrients to the distal bowel enhances a physiologic signal that improves glucose metabolism (GLP- 1) Hypothesis of the proximal bowel: Exclusion of duodenum and proximal jejunum may prevent secretion of a putative signal that promotes insuline resistance (involvement of the proximal small intestine in the physiology of IR. Hypoglycemia Insulin resistance Nesidioblastosis MECHANISM: sleeve gastrectomy Mechanisms of DM resolution after Sleeve gastrectomy RYGBP SLEEVE Early Postoperative Insulin-Resistance Changes After Sleeve Gastrectomy Nicola Basso OBES SURG (2010) 20:50 55 Karamanakos et al Ann of Surg 2008;247(3): INDICATIONS : Lower BMI in type 2 DM Rubino et al.: Effect of Duodenal Jejunal Exclusion in a Non-obese Animal Model of Type 2 Diabetes LEAN TYPE 2 DIABETEIC RATS Rubino F. Ann Surg Jan;239(1):

5 INDICATIONS : Lower BMI in type 2 DM Quote of Professor Scopinaro Why should you treat a disease September 15-16th 2008 When you can cure it!!!! 1 ste World Congress on Interventional therapies for type INDICATIONS : Lower BMI in type 2 DM Early Postoperative Outcomes of Metabolic Surgery to Treat Diabetes LAGB vs RYGBP BMI 30<>35 DM TYPE 2 % resolution 3-6 months 6-12 months BMI 3-6 months 6-12 months RYGBP 50 55,2 27,2 27,1 Lap Banding 31,8 27, ,9 P 0,0579 0,0199 <0,0001 0, Diabetes; September 15-16th 2008 From Sites Participating in the ASMBS BSCOE Program as Reported in the BOLD Eric J. DeMaria, MD, Walter J. Pories, MD Annals of Surgery Volume 252, Number 3, Sept Issues on diabetes Insulin resistance Issues on diabetes Unhealthy lifestyle and environmental factors + Metabolic syndrome Increased risk of cardiovascular disease Unhealthy lifestyle and environmental factors + Genes Environment Inflammation Free fatty acid Glucose Hyperglycaemia Healthy beta-cells Failing beta-cells Type 2 diabetes Rubino 5

6 COULD NOT REPRODUCE THE RESULT ON DM W. PORIES Insulin resistance did not change either Walter J. Pories, G. Lynis Dohm, Obes Surg Nov 18. Epub ahead of print Walter J. Pories, G. Lynis Dohm, Obes Surg Nov 18. Epub ahead of print WEIGHT REGAIN IS STRONGLY ASSOCIATED WITH RELAPSE OF DM Lower preoperative BMI is also contributing factor WEIGHT LOSS IS IMPORTANT! Possible mechanisms: -Increased calory intake -Increased fat mass -Adaptation of the gut Further research is needed Surg Obes Relat Dis DiGiorgi M, Bessler M. CALORIC RESCTRICTION is IMPORTANT BYPASS VERSUS NO OPERATION DIET ONE WEEK IDENTICAL FOR BOTH RYGBP CHANGES HORMONES INSULINE RESISTANCE IS CHANGED BY CALORY RESTRICTION CONCLUSIONS It is an absolute indication to operate on type 2 diabetes patients with a BMI > 35 We have to do it as soon as possible: beta cell function metabolic memory More knowledge about DM 2 and mechanisms of surgery will lead to Patient tailored approaches with different kind of operations Better predictive tools than BMI Untill then new indications or operation have to be conducted in trials with adequate outcome parameters JAMES M. ISBELL, NAJI N. ABUMRAD,DIABETES CARE, VOLUME 33, NUMBER 7, JULY

7 NEW DEVICES NEW DEVICES NEW OPERATIONS NEW OPERATIONS An ileal interposition with a diverted sleeve gastrectomy is an effective operation for the treatment of type 2 diabetes mellitus patients with BMI DepaulaAL, Surg Endosc 2008 Oct 2. 7