Clinical Improvement Precedes Glycemic Homeostasis After Duodenal-Jejunal Bypass for Non-Obese Type 2 Diabetes Dominique E...
Derived from Center for Disease Control and Prevention website www.cdc.gov Percent of Obese (BMI ≥ 30) in US Adults
Derived from Center for Disease Control and Prevention website www.cdc.gov Percent of Obese (BMI ≥ 30) in US Adults
<ul><li>National Hospital Discharge Survey Public-use data file and documentation. Multi-year data CD-ROM. National Center...
Current Procedures
Metabolic Syndrome <ul><li>Also Known as: </li></ul><ul><li>1. Syndrome “X” </li></ul><ul><li>2. Insulin Resistance Syndro...
Obesity Associated Conditions Diabetes Hypertension Sleep apnea Congestive heart failure Hyperlipidemia Stroke Coronary ar...
Diabetes <ul><li>Considered major public health problem – emerging as a world wide pandemic. In 1995 ~ 135 million people ...
Prevalence of Diabetes <ul><li>From 1980 through 2005, the number of adults aged 18-79 with newly diagnosed diabetes almos...
<ul><li>Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review ...
Schauer et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.   Ann Surg. 2003 Oct; 238(4): ...
Biliopancreatic Diversion (BPD) <ul><li>312 BPD, obese patients with type 2 DM were followed for pre and postoperative ser...
Biliopancreatic Diversion (BPD) Scopinaro N, Marinari GM, Camerini GB et al. Specific Effects of Biliopancreatic Diversion...
Clinical Evidence:  Bariatric Surgery & Impact on Metabolic Syndrome
Rates of Remission of Diabetes Adjustable Gastric Banding Roux-en-Y Gastric Bypass Biliopancreatic Diversion >95% (Immedia...
<ul><li>“ Gastric bypass and biliopancreatic diversion  </li></ul><ul><li>seem to achieve control of diabetes as a primary...
1995-“Who Would Have Though It? Pories et al. Annals of Surgery  <ul><li>NIDDM is no longer an uncontrollable disease </li...
Historical Perspective <ul><li>1955- Friedman  </li></ul><ul><ul><li>3  patients with poorly control DM  </li></ul></ul><u...
Rehfeld J, 2004 1967 – Gastric Bypass DISCOVERY OF GASTROINTESTINAL HORMONES
How Does Bariatric Surgery  Effect glucose homeostasis? <ul><li>Intestinal Malabsorption? </li></ul><ul><ul><li>Weight los...
1. Pathophysiology DIABETES OBESITY <ul><ul><ul><li>Excess adipose tissue increases </li></ul></ul></ul><ul><ul><ul><li>av...
2. Hormonal Changes after Bariatric Surgery
3. Anti-Incretin Insulin resistance Beta cell depletion Hyperglycemia Too Much Dumping Syndrome Nesidioblastosis Hyperinsu...
GIP and GLP-1 <ul><li>Stimulated by enteral nutrients </li></ul><ul><li>insulin secretion / action </li></ul><ul><li> -ce...
Potential Cure for Diabetes  Hypothesis Hypoglycemia <ul><ul><ul><li>Rubino et al;  Ann. Surg. 2002 </li></ul></ul></ul>
Hypothesis <ul><ul><ul><li>Rubino et al;  Ann. Surg. 2002 </li></ul></ul></ul>
Hypothesis <ul><ul><ul><li>Rubino et al;  Ann. Surg. 2002 </li></ul></ul></ul>
Hypothesis <ul><ul><ul><li>Rubino et al;  Ann. Surg.  2002 </li></ul></ul></ul>
2004:  Duodenal-Jejunal Exclusion - Foregut
2004: “ Results of our study support the hypothesis  that the bypass of duodenum and jejunum can  directly control type 2 ...
Slides taken from: DIABETES IS NO LONGER A HOPELESS DISEASE The Guilty Gut Walter Pories, MD, FACS,  Chief, Metabolic Inst...
Slides taken from: DIABETES IS NO LONGER A HOPELESS DISEASE The Guilty Gut Walter Pories, MD, FACS,  Chief, Metabolic Inst...
2006: “ This study shows that bypassing a short segment  of proximal intestine directly ameliorates type 2 diabetes,  inde...
<ul><li>Bariatric Surgery clearly has an antidiabetic effect; thought to be secondary to surgically induced weight loss an...
Animal Model of DJ Bypass and Glycemic Control <ul><li>Animal Model of non-obese type 2 diabetes; Goto-Kakizaki rats </li>...
2007-  Results of DJ Bypass on Glycemic Control <ul><li>Group 1 and Group 2 rats remained the same weight during the exper...
Leptin??? <ul><li>Adipocyte-derived hormone </li></ul><ul><li>In mice, leptin acts as a hormonal signal on the afferent li...
Cohen -SAGES 2008
Cohen -SAGES 2008
Cohen -SAGES 2008
<ul><ul><li>Double blind study: 16 patients assigned to LRYGBP and 16 Pts to LSG  </li></ul></ul><ul><ul><li>Patients reev...
<ul><li>“ PYY levels increased similarly after either procedure.  </li></ul><ul><li>The markedly reduced ghrelin levels in...
Vidal et al. Type 2 Diabetes Mellitus and the Metabolic Syndrome Following Sleeve Gastrectomy in Severely Obese Subjects. ...
<ul><li>SG is as effective as GBP in inducing remission  </li></ul><ul><li>of T2DM and the MS.  </li></ul><ul><li>SG and G...
Non-Obese Patients <ul><li>Slides taken from:  DIABETES IS NO LONGER A HOPELESS DISEASE The Guilty Gut,Walter Pories, MD, ...
<ul><li>First Clinical description of laparoscopic stomach-preserving DJB for treatment of T2DM </li></ul><ul><li>2 patien...
<ul><li>39 patients underwent laparoscopic ileal interposition into proximal jejunum via sleeve or diverted sleeve gastrec...
DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35.  Surg. Endosc.
DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35.  Surg. Endosc.
DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35.  Surg. Endosc.
DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35.  Surg. Endosc. <ul><li>Conclusi...
CLINICAL TRIAL: Duodenal-Jejeunal Bypass for Type 2 Diabetes (DJBD)  <ul><li>SUMMARY: </li></ul><ul><li>Clinical Evaluatio...
Dominican Republic 2007 <ul><li>Prospective controlled clinical trial </li></ul><ul><li>Seeking to recruit total of 50 pat...
Lutheran Medical Center Clinical Trial 2008 <ul><li>Prospective study </li></ul><ul><li>Seeking to recruit total of 50 pat...
Clinical Trial Eligibility Inclusion Criteria <ul><li>Adults age 20-65  </li></ul><ul><li>Clinical diagnosis of type II di...
Clinical Trial Eligibility Exclusion Criteria <ul><li>Diagnosis of type 1 diabetes </li></ul><ul><li>Planned pregnancy wit...
Preoperative work up <ul><li>Detailed informed consent explain to patient and </li></ul><ul><li>Baseline assessment by mul...
Operative Course <ul><li>Laparoscopic Duodenal-Jejunal bypass under GETA  </li></ul><ul><li>Preoperative prophylaxis antib...
Postoperative follow up <ul><li>Follow up with multidisciplinary team </li></ul><ul><ul><li>Surgeon, endocrinologist, prim...
Outcomes/Measures <ul><li>The primary outcome </li></ul><ul><ul><li>Reversion of hyperglycemia to euglycemia (normalizatio...
Clinical Evaluation of the Effect of Duodenal -Jejunal  Bypass on Type 2 Diabetes (June 2007) Patient Demographic, June 6,...
Results <ul><li>Overall, no complications were observed that in any way stemmed from the procedure  </li></ul><ul><li>One ...
Clinical Evaluation of the Effect of Duodenal -Jejunal  Bypass on Type 2 Diabetes (June 2007) Patient Duration of Type 2 D...
Clinical Evaluation of the Effect of Duodenal-Jejunal  Bypass on Type 2 Diabetes ( June 2007) <ul><li>HBA1c, Fasting Blood...
Clinical Evaluation of the Effect of Duodenal-Jejunal  Bypass on Type 2 Diabetes ( June 2007) <ul><li>The mean HBA1c at pr...
!!! <ul><li>One patient required insulin preop, at 6 months she was no longer on insulin and all lab work was normal </li>...
!!! <ul><li>Our Study- 1 year follow-up </li></ul><ul><li>5 patients (71%) T2DM > 10 years (10-19) </li></ul><ul><li>1 pre...
!!! <ul><li>2 patients with c-peptide <1, the HbA1c increased following the procedure </li></ul><ul><li>Both patients had ...
 
SAGES 2008 <ul><li>35 patients T2DM for 2-10 years l underwent LDJB </li></ul><ul><li>April-Nov 07 </li></ul><ul><li>15 wo...
Complications <ul><li>1 death  </li></ul><ul><li>2 intestinal obstruction </li></ul><ul><li>1 pos-operative pancreatitis <...
Results <ul><li>HbA1c decreasing from 8.9 to 6.1 and 72.3% </li></ul><ul><li>72.3% of patients had control of their hypert...
Interim Conclusions <ul><li>Very promising initial experience.  </li></ul><ul><li>The vast majority of insulin users do no...
Interim Conclusions <ul><li>What are the correct inclusion/exclusion criteria? Should we cut off at 8, 9, 10 years? </li><...
Interim Conclusions <ul><li>Don ’t  rush to withdraw medication.  </li></ul><ul><li>We add an incretin effect, but METFORM...
Interim Conclusions <ul><li>What are the appropriate limb lengths? 50/80? </li></ul><ul><li>Is it necessary to bypass the ...
What The Future Holds? <ul><li>Zhou et al.  In vivo reprogramming of adult pancreatic cells to B-cells.  Nature. October 2...
The Surgeon and the Diabetologists
Acknowledgements <ul><li>Kell Juliard </li></ul><ul><li>Martin Bluth, MD, PhD </li></ul><ul><li>Giancarlo Cires, MD </li><...
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Clinical Improvement Proceeds Glycemic Homeostasis After Duodenal-jejunal Bypass for Non-obese Type 2 Diabetes

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  • Clinical Improvement Proceeds Glycemic Homeostasis After Duodenal-jejunal Bypass for Non-obese Type 2 Diabetes

    1. 1. Clinical Improvement Precedes Glycemic Homeostasis After Duodenal-Jejunal Bypass for Non-Obese Type 2 Diabetes Dominique Elvita,DO Marc Ciaglia,DO George S. Ferzli, Jr, MS George S. Ferzli, MD, FACS Chairman of Surgery, Lutheran Medical Center Professor of Surgery, SUNY HSC Brooklyn, New York, USA
    2. 2. Derived from Center for Disease Control and Prevention website www.cdc.gov Percent of Obese (BMI ≥ 30) in US Adults
    3. 3. Derived from Center for Disease Control and Prevention website www.cdc.gov Percent of Obese (BMI ≥ 30) in US Adults
    4. 4. <ul><li>National Hospital Discharge Survey Public-use data file and documentation. Multi-year data CD-ROM. National Center for Health Statistics, 1979-1996. </li></ul><ul><li>Nguyen et al. Accelerated growth of bariatric surgery with the introduction of minimally invasive surgery. Arch Surg 2005; 140: 1198-202. </li></ul><ul><li>Griffen et al. The decline and fall of the jejunoileal bypass. Surg Gynecol Obstet 1983; 157: 301-8. </li></ul><ul><li>Shirmer et al. Bariatric Surgery Training: Getting Your Ticket Punched. J Gastrointest Surg 2007;11: 807-12. </li></ul>Popularity of Surgical Management Period or Decades Incidence of Surgery Reason for Change Late 1970’s Early 1980’s 25,000 procedures per year <ul><li>Innovative procedures </li></ul><ul><li>gastroplasty </li></ul><ul><li>loop GBP </li></ul><ul><li>jejuno-ileal bypass </li></ul>Late 1980’s 1990’s 5,000 procedures per year <ul><li>Multifactorial: </li></ul><ul><li>High M&M </li></ul><ul><li>Ineffective long-term </li></ul><ul><li>Perceived failure </li></ul><ul><li>Surgeon experience </li></ul>2000’s 80,000 to 110,000 procedures per year <ul><li>Multifactorial: </li></ul><ul><li>Laparoscopy </li></ul><ul><li>Long-term data </li></ul><ul><li>Centers of Excellence </li></ul>
    5. 5. Current Procedures
    6. 6. Metabolic Syndrome <ul><li>Also Known as: </li></ul><ul><li>1. Syndrome “X” </li></ul><ul><li>2. Insulin Resistance Syndrome </li></ul><ul><li>3. Reaven’s Syndrome </li></ul><ul><li>4. Deadly Quartet </li></ul><ul><li>5. CHAOS </li></ul><ul><li>C oronary Artery Disease </li></ul><ul><li>H ypertension </li></ul><ul><li>A dult Onset Diabetes </li></ul><ul><li>O besity </li></ul><ul><li>S troke </li></ul>
    7. 7. Obesity Associated Conditions Diabetes Hypertension Sleep apnea Congestive heart failure Hyperlipidemia Stroke Coronary artery disease Osteoarthritis Gastroesophageal reflux disease Non-alcoholic fatty liver Psychological disturbances
    8. 8. Diabetes <ul><li>Considered major public health problem – emerging as a world wide pandemic. In 1995 ~ 135 million people worldwide </li></ul><ul><li>Expected to rise to close to 300 million by 2025 </li></ul><ul><li>CDC (2008) cases of diabetes have increased to 15% in just the past two years </li></ul><ul><li>1998-Annual direct health care cost was estimated to be $60 billion in US </li></ul><ul><li>Complications </li></ul><ul><ul><li>Peripheral vascular disease (PVD) accounts for 20-30% </li></ul></ul><ul><ul><li>10% of cerebral vascular accident </li></ul></ul><ul><ul><li>Cardiovascular disease accounts for 50% of total mortality </li></ul></ul><ul><ul><li>1. Venkat et al Diabetes–a common, growing, serious, costly, and potentially preventable public health problem. Diabetes Res </li></ul></ul><ul><ul><li>Clin Pract. 2000; 5 (Suppl2): S77–S784. </li></ul></ul><ul><ul><li>2. H. King et Global burden of diabetes, 1995-2025: prevalence, numerical estimates and projections. Diabetes Care 21 (1998) </li></ul></ul><ul><ul><li>1414-1431. </li></ul></ul><ul><ul><li>3. CDC website @ www.CDC.com </li></ul></ul>
    9. 9. Prevalence of Diabetes <ul><li>From 1980 through 2005, the number of adults aged 18-79 with newly diagnosed diabetes almost tripled from 493,000 in 1980 to 1.4 million in 2005 in the United States </li></ul><ul><li>Annual number (in thousands) of new cases of diagnosed diabetes among adults aged 18-79 years, United States, 1980–2005 </li></ul>
    10. 10. <ul><li>Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004; 292: 1724-37. </li></ul><ul><li>Sjostrom L, Lindros AK, Peltonem M, Torgerson J, Bouchard C, Carlsson B, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351: 2683-93. </li></ul>Long-term Weight Control Analysis Studies Type and Size Effect on Weight Effect on Comorbidities Buchwald et al. Meta-analysis n = 22,094 pts Mean excess weight loss: 61% <ul><li>Resolution of: </li></ul><ul><li>Diabetes: 70% </li></ul><ul><li>HTN: 62% </li></ul><ul><li>Sleep apnea: 86% </li></ul>Swedish Obese Subject trial (SOS) Prospective matched cohort n = 4,047 pts <ul><li>At 10 years: </li></ul><ul><li>Med: 1.6% gain </li></ul><ul><li>Surg: 16% loss </li></ul><ul><li>Improved by surgery: </li></ul><ul><li>Diabetes </li></ul><ul><li>Lipid profile </li></ul><ul><li>HTN </li></ul><ul><li>Hyperuricemia </li></ul>
    11. 11. Schauer et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003 Oct; 238(4): 467-84 <ul><li>1160 patients underwent LRYGBP 5-year period </li></ul><ul><li>LRYGBP resulted in significant weight loss (60% percent of excess body weight loss) and resolution (83%) of T2DM </li></ul><ul><li>Fasting plasma glucose and HBA1C normalized (83%) or markedly improved (17%) in all patients </li></ul><ul><li>Patients with the shortest duration and mildest form of T2DM had a higher rate of T2DM resolution after surgery </li></ul><ul><ul><li>suggesting that early surgical intervention is warranted to increase the likelihood of rendering patients euglycemic </li></ul></ul>
    12. 12. Biliopancreatic Diversion (BPD) <ul><li>312 BPD, obese patients with type 2 DM were followed for pre and postoperative serum glucose, triglycerides, cholesterol & arterial pressure measurements </li></ul><ul><li>After BPD, fasting serum glucose fell within normal values in 310 patients; remained normal up to 10 years in all but 6 patients </li></ul><ul><li>Evidence of hypertension disappeared in majority of patients </li></ul><ul><li>Glycemic control translates into a reduced mortality for these patients as well as a low frequency of death from cardiovascular events </li></ul><ul><li>TRUE CLINICAL RECOVERY </li></ul>Scopinaro N, Marinari GM, Camerini GB et al. Specific Effects of Biliopancreatic Diversion on the Major Components of Metabolic Syndrome. Diabetes Care . 2005. 28:2406-2411
    13. 13. Biliopancreatic Diversion (BPD) Scopinaro N, Marinari GM, Camerini GB et al. Specific Effects of Biliopancreatic Diversion on the Major Components of Metabolic Syndrome. Diabetes Care . 2005. 28:2406-2411
    14. 14. Clinical Evidence: Bariatric Surgery & Impact on Metabolic Syndrome
    15. 15. Rates of Remission of Diabetes Adjustable Gastric Banding Roux-en-Y Gastric Bypass Biliopancreatic Diversion >95% (Immediate) 48% (Slow) 84% (Immediate)
    16. 16. <ul><li>“ Gastric bypass and biliopancreatic diversion </li></ul><ul><li>seem to achieve control of diabetes as a primary and </li></ul><ul><li>independent effect, not secondary </li></ul><ul><li>to the treatment of overweight.” </li></ul><ul><li>Potential of Surgery for Curing Type 2 Diabetes Mellitus. Rubino, Francesco, MD; Gagner, </li></ul><ul><li>Michel MD, FACS, FRCSC Annals of Surgery; 236 (5): 554-559, November 2002 </li></ul>2002: Antidiabetic Effect of Bariatric Surgery: Direct or Indirect?
    17. 17. 1995-“Who Would Have Though It? Pories et al. Annals of Surgery <ul><li>NIDDM is no longer an uncontrollable disease </li></ul><ul><li>The correction on NIDDM occurs within days following gastric bypass, long before significant weight loss has occurred </li></ul><ul><li>Decrease caloric intake and changes in incretin stimulation of the islets by the gut may play a role </li></ul>
    18. 18. Historical Perspective <ul><li>1955- Friedman </li></ul><ul><ul><li>3 patients with poorly control DM </li></ul></ul><ul><ul><li>3-4 days after subtotal gastrectomy all 3 pateints showed an improvement in their DM </li></ul></ul><ul><ul><ul><li>Occurred sooner than associated weight loss </li></ul></ul></ul><ul><ul><ul><li>Patients later regained their weight without an associated loss of glucose control or glycosuria </li></ul></ul></ul><ul><li>Mingrone 1977 : Case report </li></ul><ul><ul><li>Young, non obese woman with DM who underwent BPD for chylomicronemia </li></ul></ul><ul><ul><li>Plasma insulin and blood glucose levels normalized within 3 months </li></ul></ul><ul><li>Bittner –1981- subtotal gastrectomy and gastrointestinal reconstructions that excluded duodenal passage (B2 and RYGB </li></ul><ul><ul><li>Lowered plasma glucose and insulin </li></ul></ul><ul><ul><li>Conclusion: Plasma glucose and insulin fall rapidly post-operatively </li></ul></ul><ul><ul><ul><li>antidiabetic medications can be reduced or stopped shortly after gastrointestinal bypass interventions </li></ul></ul></ul><ul><ul><li>Rubino F. Bariatric Surgery:effects on glucose homeostasis. Curr. Opin. Clin. Nutr. Metab. Care 9: 497-507 </li></ul></ul><ul><ul><li>Bittner R. Homeostasis of glucose and gastric resection: the influence of food passage through the duodenum Z Gastroenterology 1981; 19: 698-707. </li></ul></ul><ul><ul><li>Friedman NM et al. The amelioration of diabetes mellitus following subtotal gastrectomy. Surg. Gynecol. Obstetr. 1955; 100:201-204 </li></ul></ul>
    19. 19. Rehfeld J, 2004 1967 – Gastric Bypass DISCOVERY OF GASTROINTESTINAL HORMONES
    20. 20. How Does Bariatric Surgery Effect glucose homeostasis? <ul><li>Intestinal Malabsorption? </li></ul><ul><ul><li>Weight loss reduces insulin resistance </li></ul></ul><ul><ul><li>Glucose malabsorption reduces stress on islet cells </li></ul></ul><ul><ul><li>Fat malabsorption reduces circulating free fatty acids and improves insulin sensitivity </li></ul></ul><ul><li>Hormonal Changes? </li></ul><ul><ul><li>Re-routing of food alters the dynamic of gut-hormone secretion </li></ul></ul><ul><ul><ul><li>Decrease in plasma levels of leptin & insulin </li></ul></ul></ul><ul><ul><ul><li>Increased levels of adiponectin & peptide YY3-36 </li></ul></ul></ul><ul><ul><ul><li>Increased levels of glucagon-like peptide 1 (GLP-1) </li></ul></ul></ul><ul><li>Rearrangement of GI anatomy? </li></ul><ul><ul><ul><li>“ Hindgut hypothesis” </li></ul></ul></ul><ul><ul><ul><li>“ Foregut hypothesis” </li></ul></ul></ul>
    21. 21. 1. Pathophysiology DIABETES OBESITY <ul><ul><ul><li>Excess adipose tissue increases </li></ul></ul></ul><ul><ul><ul><li>available triglyceride stores </li></ul></ul></ul><ul><ul><ul><li>Breakdown of TG leads to overabundance </li></ul></ul></ul><ul><ul><ul><li>of circulating fatty acids </li></ul></ul></ul><ul><ul><ul><li>INCREASED FATTY ACIDS </li></ul></ul></ul>INSULIN RESISTANCE INCREASES HEPATIC TRIGLYCERIDE SYNTHESIS & PRODUCTION OF VLDL LOSS OF VASODILATORY EFFECT OF INSULIN PRESERVED SODIUM REABSORPTION HYPERCHOLESTEROLEMIA HYPERTENSION
    22. 22. 2. Hormonal Changes after Bariatric Surgery
    23. 23. 3. Anti-Incretin Insulin resistance Beta cell depletion Hyperglycemia Too Much Dumping Syndrome Nesidioblastosis Hyperinsulinemia Hypoglycemia Not Enough TYPE 2 DIABETES
    24. 24. GIP and GLP-1 <ul><li>Stimulated by enteral nutrients </li></ul><ul><li>insulin secretion / action </li></ul><ul><li> -cell proliferation </li></ul>… Anti-Incretin <ul><li>Stimulated by enteral nutrients </li></ul><ul><li>insulin secretion / action </li></ul><ul><li> -cell proliferation </li></ul>Anti-incretin
    25. 25. Potential Cure for Diabetes Hypothesis Hypoglycemia <ul><ul><ul><li>Rubino et al; Ann. Surg. 2002 </li></ul></ul></ul>
    26. 26. Hypothesis <ul><ul><ul><li>Rubino et al; Ann. Surg. 2002 </li></ul></ul></ul>
    27. 27. Hypothesis <ul><ul><ul><li>Rubino et al; Ann. Surg. 2002 </li></ul></ul></ul>
    28. 28. Hypothesis <ul><ul><ul><li>Rubino et al; Ann. Surg. 2002 </li></ul></ul></ul>
    29. 29. 2004: Duodenal-Jejunal Exclusion - Foregut
    30. 30. 2004: “ Results of our study support the hypothesis that the bypass of duodenum and jejunum can directly control type 2 diabetes and not secondarily to weight loss or treatment of obesity.” Effect of Duodenal-Jejunal Exclusion in a Non-obese Animal Model of Type 2 Diabetes: A New Perspective for an Old Disease. Rubino, Francesco, MD; Marescaux, Jacques MD, FRCS Annals of Surgery; 239 (1): 1-11, January 2004
    31. 31. Slides taken from: DIABETES IS NO LONGER A HOPELESS DISEASE The Guilty Gut Walter Pories, MD, FACS, Chief, Metabolic Institute East Carolina University Greenville, North Carolina 2006:
    32. 32. Slides taken from: DIABETES IS NO LONGER A HOPELESS DISEASE The Guilty Gut Walter Pories, MD, FACS, Chief, Metabolic Institute East Carolina University Greenville, North Carolina 2006:
    33. 33. 2006: “ This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut.” The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes. Rubino, Francesco, MD; Forgione, Antonello, MD; Cummings, David E MD; Vix, Michel MD; Gnuli, Donatella MD; Mingrone, Geltrude MD; Castagneto, Marco, MD (S); Marescaux, Jacques MD, FRCS Annals of Surgery; 244 (5): 741-749, November 2006
    34. 34. <ul><li>Bariatric Surgery clearly has an antidiabetic effect; thought to be secondary to surgically induced weight loss and decreased caloric intake </li></ul><ul><li>But, how do we explain the finding that glycemic control occurs within days, before significant weight loss has been achieved??? </li></ul><ul><ul><li>Direct effect of the surgical bypass of proximal intestines </li></ul></ul><ul><ul><li>Hormonal Regulation of Glucose Metabolism </li></ul></ul><ul><ul><ul><li>Insulin, glucagons-like peptide (GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon and leptin </li></ul></ul></ul>Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007): 221-224 2007: Pacheco Bypass & Glucose Metabolism
    35. 35. Animal Model of DJ Bypass and Glycemic Control <ul><li>Animal Model of non-obese type 2 diabetes; Goto-Kakizaki rats </li></ul><ul><li>Twelve (12-14 wk old) rats randomly underwent </li></ul><ul><li>gastrojejeunal bypass or no intervention </li></ul><ul><li>* All fed with same type of diet </li></ul><ul><li>* All fed with same amount of diet </li></ul><ul><li>* Pre-op, post-op 1 wk & 1 month </li></ul><ul><li>weight assessment & fasting glycemia </li></ul><ul><li>* Oral Glucose Tolerance Test performed at each </li></ul><ul><li>time point </li></ul><ul><li>* Hormone levels were measured after 20 minutes of oral </li></ul><ul><li>overload </li></ul>Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007):221-224
    36. 36. 2007- Results of DJ Bypass on Glycemic Control <ul><li>Group 1 and Group 2 rats remained the same weight during the experiment </li></ul><ul><li>OGTT improved in DJ bypass group </li></ul><ul><li>Glucose levels were better at 1 week & 1 month after DJ bypass in all times of OGTT (basal, 10 min, 120 min) </li></ul><ul><li>Post-oral glucose load levels of glucagon, insulin, GLP-1 and GIP remained unchanged in both groups </li></ul><ul><li>In DJ bypass group there is a significant decrease in leptin levels noted </li></ul>Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007): 221-224
    37. 37. Leptin??? <ul><li>Adipocyte-derived hormone </li></ul><ul><li>In mice, leptin acts as a hormonal signal on the afferent limb of a negative feedback loop between the adipose tissue and hypothalmic centers </li></ul><ul><li>Physiological increase in plasma leptin has been shown to significantly inhibit glucose-stimulated insulin secretion in vivo and to determine insulin resistance </li></ul>Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007): 221-224
    38. 38. Cohen -SAGES 2008
    39. 39. Cohen -SAGES 2008
    40. 40. Cohen -SAGES 2008
    41. 41. <ul><ul><li>Double blind study: 16 patients assigned to LRYGBP and 16 Pts to LSG </li></ul></ul><ul><ul><li>Patients reevaluated on the 1st, 3rd, 6th, and 12th mos </li></ul></ul><ul><ul><li>Results: </li></ul></ul><ul><ul><ul><li>No change in ghrelin levels after LRYGBP Significant decrease in ghrelin after LSG ( P < 0.0001) </li></ul></ul></ul><ul><ul><ul><li>Fasting PYY levels increased after either surgical procedure ( P <= 0.001) </li></ul></ul></ul><ul><ul><ul><li>Appetite decreased in both groups but to a greater extend after LSG </li></ul></ul></ul>Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Karamanakos et al Ann Surg . 2008 Mar; 247(3): 401-7.
    42. 42. <ul><li>“ PYY levels increased similarly after either procedure. </li></ul><ul><li>The markedly reduced ghrelin levels in addition to increased </li></ul><ul><li>PYY levels after LSG, are associated with greater appetite </li></ul><ul><li>suppression and excess weight loss compared with LRYGBP” </li></ul><ul><li>March 2008: Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after </li></ul><ul><li>Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Karamanakos et al Ann Surg. 2008 Mar; </li></ul><ul><li>247(3): 401-7. </li></ul>March 2008:
    43. 43. Vidal et al. Type 2 Diabetes Mellitus and the Metabolic Syndrome Following Sleeve Gastrectomy in Severely Obese Subjects. Obes. Surg. June 2008 <ul><li>12 mos prospective study 9 severely obese T2DM patients LSG (SG; n = 39) or LRYGP (GBP; n = 52) </li></ul><ul><li>Matched for DM duration, type of DM treatment, and glycemic control </li></ul><ul><li>Results </li></ul><ul><ul><li>T2DM resolved 84.6% SG and (84.6%) GBP (p = 0.618) </li></ul></ul><ul><ul><li>Weight loss was not associated with T2DM resolution after SG or GBP </li></ul></ul><ul><ul><li>Shorter DM duration and DM treatment and glycemic control associated with both groups </li></ul></ul>
    44. 44. <ul><li>SG is as effective as GBP in inducing remission </li></ul><ul><li>of T2DM and the MS. </li></ul><ul><li>SG and GBP represent a successful an integrated strategy for the management of the different cardiovascular risk components of the MS in subjects with T2DM </li></ul><ul><li>Type 2 Diabetes Mellitus and the Metabolic Syndrome Following Sleeve Gastrectomy in Severely Obese </li></ul><ul><li>Subjects. Obes. Surg. 2008, Vidal et al </li></ul>June 2008
    45. 45. Non-Obese Patients <ul><li>Slides taken from: DIABETES IS NO LONGER A HOPELESS DISEASE The Guilty Gut,Walter Pories, MD, FACS </li></ul>
    46. 46. <ul><li>First Clinical description of laparoscopic stomach-preserving DJB for treatment of T2DM </li></ul><ul><li>2 patients with >12 mos f/u (13/15 mos) </li></ul><ul><li>By 5 th week of surgery, both patients were euglycemic and free of all antidiabetic medications </li></ul><ul><li>Conclusion: </li></ul><ul><ul><li>LDJB is a feasible and safe </li></ul></ul><ul><ul><li>could represent valuable therapeutic option </li></ul></ul>
    47. 47. <ul><li>39 patients underwent laparoscopic ileal interposition into proximal jejunum via sleeve or diverted sleeve gastrectomy </li></ul><ul><ul><li>BMI < 35 </li></ul></ul><ul><ul><li>All had type II DM for at least 3 years </li></ul></ul><ul><ul><ul><li>Mean operative time was 185 minutes </li></ul></ul></ul><ul><ul><ul><li>Mean post-op follow up was 7 months </li></ul></ul></ul><ul><li>87% of patients discontinued preop oral hypoglycemics, insulin or both </li></ul><ul><li>Hemoglobin A1c decreased from 8.8% to 6.3% </li></ul><ul><li>All but one patient experienced normalization of cholesterol </li></ul>DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc.
    48. 48. DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc.
    49. 49. DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc.
    50. 50. DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc.
    51. 51. DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc. <ul><li>Conclusion: </li></ul><ul><ul><li>Laparoscopic ileal interposition via either a sleeve gastrectomy or diverted sleeve gastrectomy seems to be a promising procedure for the control of T2DM and the metabolic syndrome </li></ul></ul>
    52. 52. CLINICAL TRIAL: Duodenal-Jejeunal Bypass for Type 2 Diabetes (DJBD) <ul><li>SUMMARY: </li></ul><ul><li>Clinical Evaluation of the Effect of Duodenal-Jejunal Bypass on Type 2 Diabetes </li></ul><ul><li>FACILITY: </li></ul><ul><li>Center for Advance Medicine </li></ul><ul><li>Santo Domingo, Dominican Republic </li></ul><ul><li>STUDY OFFICIALS/INVESTIGATORS: </li></ul><ul><li>George Ferzli, MD, FACS - Study Principal Investigator, </li></ul><ul><li>SUNY Downstate, Brooklyn, New York, USA </li></ul><ul><li>Abel Gonzalez, MD - Center for Advanced Medicine, </li></ul><ul><li>Santo Domingo, Dominican Republic </li></ul><ul><li>Martin Bluth, MD, PhD - Director of Research, Assistant Professor, </li></ul><ul><li>Departments of Surgery and Pathology, Brooklyn, NY USA) </li></ul>
    53. 53. Dominican Republic 2007 <ul><li>Prospective controlled clinical trial </li></ul><ul><li>Seeking to recruit total of 50 patients </li></ul><ul><li>www. clinicaltrials .gov </li></ul><ul><li>Unique Protocol ID: AS07006 </li></ul><ul><li>Clinicaltrials.gov ID: NCT00487526 . </li></ul>
    54. 54. Lutheran Medical Center Clinical Trial 2008 <ul><li>Prospective study </li></ul><ul><li>Seeking to recruit total of 50 patients </li></ul><ul><li>www. clinicaltrials .gov </li></ul><ul><li>ID: NCT00694278, LMC 95 </li></ul>
    55. 55. Clinical Trial Eligibility Inclusion Criteria <ul><li>Adults age 20-65 </li></ul><ul><li>Clinical diagnosis of type II diabetes: </li></ul><ul><ul><li>a) A normal or high C-peptide level (to exclude type 1 diabetes) (>.9ng/ml) </li></ul></ul><ul><ul><li>b) A random plasma glucose of 200mg/dl or more with typical symptoms of diabetes </li></ul></ul><ul><ul><li>c)A fasting plasma glucose of 126mg/dl or more on more than one occasion </li></ul></ul><ul><li>BMI 22-34 KG/m2, </li></ul><ul><li>Patients on oral hypoglycemic medications or insulin to control T2DM Inadequate control of diabetes as defined as HbA1c>7.5 </li></ul><ul><li>No contraindications for surgery or general anesthesia </li></ul><ul><li>Ability to understand and describe the mechanism of action and risks and benefits of the operation </li></ul>
    56. 56. Clinical Trial Eligibility Exclusion Criteria <ul><li>Diagnosis of type 1 diabetes </li></ul><ul><li>Planned pregnancy within 2 years of entry into the study </li></ul><ul><li>Previous gastric or esophageal surgery, immunosuppressive drugs including corticosteroids, coagulopathy, anemia, any contraindication to laparoscopic gastric bypass or medical hypoglycemic therapy </li></ul><ul><li>Severe concurrent illness likely to limit life (e.g. cancer) or requiring extensive disorder (e.g. pancreatic insufficiency, Celiac sprue, or Crohn’s disease) </li></ul><ul><li>Pre-existing major complications of diabetes, significant proteinuria (>250mg/dl), severe proliferate retinopathy, severe neuropathy or clinical diagnosis of gastropathy </li></ul><ul><li>MI in the previous year </li></ul><ul><li>Unable to comply with study requirements, follow-up or give verbal consent </li></ul><ul><li>Liver cirrhosis </li></ul><ul><li>Previous abdominal surgery </li></ul>
    57. 57. Preoperative work up <ul><li>Detailed informed consent explain to patient and </li></ul><ul><li>Baseline assessment by multidisciplinary surgical team </li></ul><ul><ul><li>Surgeon, primary physician, endocrinologist, cardiologist, gastroenterologist, psychiatrist, nutritionist </li></ul></ul><ul><li>Routine work-up and blood work </li></ul><ul><ul><li>(CBC, electrolytes, serum creatinine, fasting glucose, HbA 1c , fasting lipid profile (HDL and LDL cholesterol, triglycerides), free fatty acids, leptin, insulin like growth factor 1 (ILGF-1), Glucagon, Glucagon-like peptide 1 (GLP-1), CCK, FFA, Cholesterol, Ghrelin, C-peptide and Gastro-inhibitory peptide (GIP) levels. ) </li></ul></ul><ul><li>Studies </li></ul><ul><ul><li>Electrocardiogram (ECG), chest radiograph, and Esophagogastroduodenoscopy (EGD), PFT’S (if indicated) </li></ul></ul>
    58. 58. Operative Course <ul><li>Laparoscopic Duodenal-Jejunal bypass under GETA </li></ul><ul><li>Preoperative prophylaxis antibiotic (Ancef or Clinda in PCN allergy) </li></ul><ul><li>Sequential compression devices for deep venous thrombosis (DVT) prophylaxis in addition to LMWH (5,000units SQ). </li></ul><ul><li>Operative/Intraoperative data </li></ul><ul><ul><li>OR time, EBL, complications, unusual findings </li></ul></ul><ul><li>NPO until upper gastrointestinal (UGI) on POD#1 </li></ul><ul><li>Clear fluids are begun following the UGI study, and continue for 5-7 days </li></ul><ul><li>Patient follow up with nutritionist for dietary guidelines </li></ul>
    59. 59. Postoperative follow up <ul><li>Follow up with multidisciplinary team </li></ul><ul><ul><li>Surgeon, endocrinologist, primary care physician and nutritionist at 2 weeks, 4 weeks, 3 months, and from then on at intervals of 3 months or more often if necessary, for 2 years </li></ul></ul><ul><li>Blood drawn for fasting glucose and fasting insulin on days 2 and 7 and at 2 weeks and 4 weeks and 3 months after initiation of treatment </li></ul><ul><li>Nutritionist follow up – continue to puree diet </li></ul><ul><li>Attend support group </li></ul>
    60. 60. Outcomes/Measures <ul><li>The primary outcome </li></ul><ul><ul><li>Reversion of hyperglycemia to euglycemia (normalization of HbA 1c to <7%) </li></ul></ul><ul><li>Secondary outcomes </li></ul><ul><ul><li>- lipid profiles, and C-peptide </li></ul></ul>
    61. 61. Clinical Evaluation of the Effect of Duodenal -Jejunal Bypass on Type 2 Diabetes (June 2007) Patient Demographic, June 6, 2007 <ul><li>LDJB was performed successfully in 7 patients </li></ul><ul><li>Mean age of 43.3 range (33-52) </li></ul><ul><li>Limb was 75cm/75cm </li></ul><ul><li>Operative time average 98 min </li></ul><ul><li>Length of stay 3 days </li></ul>
    62. 62. Results <ul><li>Overall, no complications were observed that in any way stemmed from the procedure </li></ul><ul><li>One patient developed a liver abscess </li></ul><ul><ul><li>required drainage unrelated to the procedure </li></ul></ul><ul><li>All patients consistently felt relief from their preoperative symptoms. </li></ul><ul><li>No deaths </li></ul>
    63. 63. Clinical Evaluation of the Effect of Duodenal -Jejunal Bypass on Type 2 Diabetes (June 2007) Patient Duration of Type 2 Diabetes Pre-Operative Medication 1 Year Medication Requirement #1 19 Metformin 850mg One tablet daily Metformin 850 mg half tablet daily #2 10 30/10 Units Insulin 30/10 Units Insulin #3 12 40/20/20/20 Units Insulin 30 Units occasionally at night #4 12 2 Metformin 850mg daily; 40/20 Units Insulin 1 Metformin 850mg daily; 5 Units n occasionally #5 12 40/20 Units Insulin 5 Units Insulin three times per week #6 * 6 20/12 Units Insulin No Medication #7 4 Clormin 1000mg daily; 30/20 Units Insulin Diaformin 500mg daily; 30/20 Units Insulin
    64. 64. Clinical Evaluation of the Effect of Duodenal-Jejunal Bypass on Type 2 Diabetes ( June 2007) <ul><li>HBA1c, Fasting Blood Glucose (FBG), Triglycerides (TG), Cholesterol (Chol) and C-peptide (Cpep) were measured at pre-op and 1 year </li></ul><ul><li>Patient nos. 3, 4and 7 demonstrated marked drop (2.8 – 4.3%) in their HbA1c values through one year post op compared with pre op values, where as only 2/3 of these patients (3 &4) had reductions (>100mg/dl) in their FBG levels. </li></ul><ul><li>In contrast, TG levels increased in these two patients. Interestingly, some patients demonstrated an increase in HbA1c (patient nos. 1&2), FBG (patient nos. 1&7), TG (patient nos. 1&6), and c-pep (patient nos. 1&7) at one-year post op compared with pre-op values. </li></ul>HBA1C FBG Cholesterol TG C-Peptide     Pre-op 1w 3m 1yr Pre-op 1w 3m 1yr Pre-op 1w 3m 1yr Pre-op 1w 3m 1yr Pre-op 1w 3m 1yr #1   8 11.8 9.4 12 256 68 218 315 180 143 164 164 58 44 76 87 <0.5 2.2 1.2 1.3 #2 6.7 8.6 11.9 8.5 180 232 324 123 157 171 157 132 88 143 99 84 1.2 0.9 1.1 0.2 #3 11.8 12.3 8.8 7.5 252 202 176 90 160 152 138 141 70 52 93 98 2.5 1.8 2.1   2.2 #4 11.2 8.4 7.7 7.7 195 211 88 84 158 156 151 151 97 77 74 109 1.8 1.9 0.5   1.2 #5 9.4 12.3 9.8 8.6 181 184 95 110 227 204 200   211 195 136 303   119 <0.5 <0.5   <0.5 <0.5 #6 6.6 6.6 8.1 6.3 112 163 84 63 179 157 171 271  44 58 47   276 1.3 1.3 0.5 0.2 #7 11.7 13.4 11.7 8.9 286 210 322 299 225 199 263 232 235 120 224 118 1.8 1.4 2.6 2.3
    65. 65. Clinical Evaluation of the Effect of Duodenal-Jejunal Bypass on Type 2 Diabetes ( June 2007) <ul><li>The mean HBA1c at pre-op and 1 year was 9.371 and 8.500 respectively </li></ul><ul><li>FBG at pre-op and 1 year were 208 and 154 respectively for the seven patients (p=0.057) </li></ul><ul><li>Lipid profiles improved with lower total cholesterol levels and triglycerides 1 year </li></ul>  Mean (SEM) Pre vs post op Correlation P value* HBA1C Pre-op 9.371 (0.85) -0.040 0.933 HBA1C 1yr 8.500 (0.67) FBG Pre-op 208.86 (22.50 0.74 0.057 FBG 1YR 154.86 (39.9) Cholesterol preop 183.71 (11.5) 0.632 0.128 Cholesterol 1yr 186.00 (19.9) TG pre-op 112.43 (27.7) -0.245 0.596 TG 1yr 127.29 (25.3) Cpep pre-op 1.343 (0.29) -0.245 0.205 Cpep 3 months 1.200 (0.32)
    66. 66. !!! <ul><li>One patient required insulin preop, at 6 months she was no longer on insulin and all lab work was normal </li></ul><ul><li>She became pregnant at 6 months following surgery </li></ul><ul><li>Her diabetes returned and her insulin requirement is at the pre-op level </li></ul><ul><li>It is unclear whether she had resolution of her T2DM or had developed gestational diabetes requiring insulin for her pregnancy at the 1-year follow-up </li></ul>
    67. 67. !!! <ul><li>Our Study- 1 year follow-up </li></ul><ul><li>5 patients (71%) T2DM > 10 years (10-19) </li></ul><ul><li>1 pre oral/insulin-free from medication at 1 yr </li></ul><ul><li>2 required less dosages </li></ul><ul><li>All 5 patients –no symptoms and improved state of health </li></ul>
    68. 68. !!! <ul><li>2 patients with c-peptide <1, the HbA1c increased following the procedure </li></ul><ul><li>Both patients had decreased in medication requirements </li></ul>
    69. 70. SAGES 2008 <ul><li>35 patients T2DM for 2-10 years l underwent LDJB </li></ul><ul><li>April-Nov 07 </li></ul><ul><li>15 women, 20 men </li></ul><ul><li>Comorbidities </li></ul><ul><ul><li>75% with HTN </li></ul></ul><ul><ul><li>58% Hypercholesteremia </li></ul></ul><ul><ul><li>62.5% Hypertriglyceremia </li></ul></ul><ul><li>Mean OR time = 46 minutes (33-78 min) </li></ul><ul><li>Hospital stay 30 hrs –81 days </li></ul><ul><li>PPI for 90 days </li></ul><ul><li>Patients kept on metformin/glimeperide (metformin withdrawn when HBA1c <6) </li></ul>Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis).
    70. 71. Complications <ul><li>1 death </li></ul><ul><li>2 intestinal obstruction </li></ul><ul><li>1 pos-operative pancreatitis </li></ul><ul><li>2 intracavitary bleeding </li></ul>Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis).
    71. 72. Results <ul><li>HbA1c decreasing from 8.9 to 6.1 and 72.3% </li></ul><ul><li>72.3% of patients had control of their hypertension: reduced sympathetic outflow? </li></ul><ul><li>13/35 patients reported food intolerance: 8/13 required admission (no women) </li></ul><ul><li>Oral Ginger and sildenafil are very helpful </li></ul><ul><li>75% complained of post-prandial sleepiness </li></ul><ul><ul><li>These side effects may be attributed to gastroparesis and the postulated diminished sympathetic outflow, a result of central leptin suppression and duodenal bypass </li></ul></ul>Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis)
    72. 73. Interim Conclusions <ul><li>Very promising initial experience. </li></ul><ul><li>The vast majority of insulin users do not use it anymore very early in the post-op. </li></ul><ul><li>In most of those patients with overweight or grade 1 obesity, weight loss is not a major player regarding the control of T2DM, as some had no weight modification or regained weight and there was no recurrence. </li></ul><ul><li>In patients with higher BMIs, but still under 35 (32-35), it seems that major weight loss is needed to achieve control of T2DM. </li></ul>
    73. 74. Interim Conclusions <ul><li>What are the correct inclusion/exclusion criteria? Should we cut off at 8, 9, 10 years? </li></ul><ul><li>Time of T2DM history does not seem important, but C peptide below 1 YES!!! </li></ul>
    74. 75. Interim Conclusions <ul><li>Don ’t rush to withdraw medication. </li></ul><ul><li>We add an incretin effect, but METFORMIN helps to decrease hepatic defective glucose production. </li></ul><ul><li>What is the antidiabetes mechanism? </li></ul><ul><li>Cold pressor test before and after duodenal exclusion to assess sympathetic response ? </li></ul>
    75. 76. Interim Conclusions <ul><li>What are the appropriate limb lengths? 50/80? </li></ul><ul><li>Is it necessary to bypass the entire duodenum? </li></ul><ul><ul><li>If yes, how can we assess that? </li></ul></ul><ul><ul><li>Does it make any difference? </li></ul></ul><ul><li>Do we need complex operations in this subset of patients? </li></ul><ul><ul><li>Are the mortality/ complication rates reasonable? </li></ul></ul><ul><li>Will an added sleeve gastrectomy in selected patients be needed to avoid gastroparesis, mainly in those with BMI>32? </li></ul><ul><ul><li>Or is a LRYGB more adequate? </li></ul></ul>
    76. 77. What The Future Holds? <ul><li>Zhou et al. In vivo reprogramming of adult pancreatic cells to B-cells. Nature. October 2008 </li></ul><ul><li>Transcription factors Ngn3, Pdx1 and Mafa reprograms differentiated pancreatic cells in adult mice into cells that closely resemble Beta cells… </li></ul><ul><li>Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard University. </li></ul>
    77. 78. The Surgeon and the Diabetologists
    78. 79. Acknowledgements <ul><li>Kell Juliard </li></ul><ul><li>Martin Bluth, MD, PhD </li></ul><ul><li>Giancarlo Cires, MD </li></ul><ul><li>Rosemarie E Hardin, MD </li></ul><ul><li>Joel Ricci, MD </li></ul>

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