Daniel Tat-ming Chung Princess Margaret Hospital 16 th April 2011 JHSGR

  for weight  Surgical procedures designed to produce substantial weight loss.  Most effective therapy for severe obesity  Reduction of morbidity and mortality  Quality of life improvement

Oriental Daily 15 th April 2011

 In 2000: >171 million people worldwide suffer from diabetes = 2.8% of the population  Doubled by 2030 Narayan et al. Diabetic Care 2006 Greatest increase in prevalence: Asia and Africa Wdiabetes: estimates for 2000 and projections ild et al. "Global prevalence of for 2030". Diabetes Care 2004

Gaede et al. NEJM 2008

 Insulin levels / HbA1c / Fasting glucose declined significantly postoperatively No. of Study No. of Patient Completely Resolved Resolved or Improved Buchwald et al. JAMA %86.0% Buchwald et al. Am J Med , %86.6% Buchwald et al. Am J Med 2009

Sjostrom et al. N Engl J Med 2004

 0.1% - 2%  Gastric banding: 0.1%

 Released on 28 March 2011

“Bariatric surgery may be considered for adults with BMI 35 kg/m2 and type 2 diabetes, especially if the diabetes or associated comorbidities are difficult to control with lifestyle and pharmacologic therapy.’’ ADA Standard of Medical Care in Diabetes 2011

Pories et al. Ann Surg 1995

 Wickremesekera et al. Loss of Insulin Resistance after Roux-en-Y Gastric Bypass Surgery: a Time Course Study. Obesity Surg 2005  “The changes in in insulin resistance seen after gastric bypass, which are responsible for the resolution or improvement of type 2 diabetes occur within 6 days of the surgery, before any appreciable weight loss has occurred “

WEIGHT LOSS RELATEDWEIGHT LOSS INDEPENDENCE  Morbidly obese subjects with normal glucose tolerance  Studied at 4 and 14 months  Insulin-mediated glucose disposal improved in proportion to the degree of weight loss  Pereira et al  Type 2 diabetic individuals improves glucose disposal much more significantly than in a comparable group where weight loss was induced by diet  Equivalent weight loss by RYGB or by diet in two groups of matched morbidly obese patients with type 2 diabetes produced changes in incretin levels which were strikingly different  Laferrere et al 2008

 Dramatic and rapid recover of insulin sensitivity which can be observed a few days after the operation when the weight loss is not significantly changed  Guidone et al Scopinaro et al. 2005

 Goto-Kakizaki (GK) rat  a non-obese Wistar substrain  develops Type 2 diabetes mellitus early in life.  The model was developed by Goto and Kakizaki at Tohoku University, Sendai, Japan in  ? Anatomical rearrangement ? Decreased caloric intake ? Malabsorption

Rubino et al. Effect of Duodenal–Jejunal Exclusion in a Non-obese Animal Model of Type 2 Diabetes - A New Perspective for an Old Disease. Ann Surg 2004

 Early delivery of nutrients to the distal intestine enhances the incretin hormone effect  Glucagon-like peptide-1 (GLP-1) secreted by L-cell in distal ileum and colon Distal ileum and Colon

Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats Strader et al. 2005

 After 3 weeks, all 5 patients with T2DM preoperatively had normal blood glucose levels without medication.

 No conclusive evidence that RYGB increases the production of GLP-1  GLP-1 incraeses after RYGB: ? late adaptive phenomenon  Role in early improvement of DM remission is questionable  Prevention of duodeal passage of nutrient improve glucose tolerance only in diabetic patients  Glucose tolerance may actually deteriorate if the procedure is performed in non- diabetics  Schwarz et al  Rubino et al. 2006

 Aberrant gastrointestinal signaling unique to the diabetic state  Possibly removed when the proximal intestine is bypassed Rubino et al. The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes. Ann Surg 2006.

27 < BMI < 3325 < BMI < 35  Chiellini et al EFFECTS OF BILIOPANCERATIC DIVERSION ON TYPE 2 DIABETES IN PATIENTS WITH BMI 25 TO 35 Scopinaro et al. 2011

Buchwald et al. JAMA 2004: Hyperlipidemia improved in 70% or more of patients  Hypertension was resolved in 61.7% of patients and resolved or improved in 78.5%.  Lower with LAGB (43%, 27% respectively)  Buchwald et al. JAMA 2004  521 hypertensive RYGB patients: HT resolved in 69% in one year and 66% at 5-7 years after opereation  Sugerman et al. Ann Surg 2003

 Placed in the stomach to mimic restriction  Placed in the trans-pyloric area to delay or regulate gastric emptying  Endoscopically placed devices hysically fixed to the upper GI tract to mimic proximal gastric restriction of the LAGB  Endoluminal impervious sleeves to bypass the gastro- duodenal upper jejunal area to mimic the RYGB, or bypass the duodenum and proximal jejunum to mimic the DJB  Laparoscopic procedures to place novel electronic gastric or gastro-duodenal motility stimulators, and vagal nerve blocking devices

 Bariatric  metabolic surgery  Distal vs Anti-incretin hypothesis  Pathophysiology of type 2 DM  Application on non-obese DM patient

Adams et al. NEJM 2007

 Diabetes and insulin resistance revert after BPD also in normal weight or overweight individuals  Muscelli et al. 2005

 Duodenal-jejunal Bypass  Geloneze et al. Surgery for nonobese type 2 diabetic patients: an interventional study with duodenal-jejunal exclusion. Obesity Surgery  At 24 weeks after surgery, patients experienced greater reductions on FG (14% vs. 7% on CG), A1C (from 8.78 to 7.84 in GJB-p<0.01 and 8.93 to 8.71 in CG; p<0.05 between groups) and reductions on average daily insulin requirement (93% vs. 29%, p<0.01). Ten patients stopped insulin usage in GJB but they remain taking oral medications. No differences were observed in both groups regarding BMI, body distribution and composition, blood pressure, and lipids.

 Bariatric surgery can be associated with substantial other health benefits including improvement or normalisation of hyperglycaemia. hyperlipidaemia, blood pressure, obstructive sleep apnoea and improved quality of life.  Colquitt et al. Surgery for obesity. Cochrane Database Syst Rev 2009  the name “bariatric- metabolic surgery” is emerging as a more appropriate name  In view of the broad benefits of weight loss and the growing evidence that some bariatric procedures provide metabolic changes that cannot be explained completely by their effects on body weight alone  Pories et al. Etiology of type II diabetes mellitus: role of the foregut. World J Surg 2001

 inadequate insulin production and action and results in hyperglycaemia  associated with multiple other dysfunctions involving  lipid metabolism  oxidative stress  inflammation and  haemato-rheology  In addition obesity, by itself, generates similar cardio- metabolic dysfunction  Van Gaal et al. Mechanisms linking obesity with cardiovascular disease. Nature 2006