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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
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
[object Object],[object Object],[object Object],[object Object],Popularity of Surgical Management Period or Decades Incidence of Surgery Reason for Change Late 1970’s  Early 1980’s 25,000 procedures per year ,[object Object],[object Object],[object Object],[object Object],Late 1980’s 1990’s 5,000 procedures per year ,[object Object],[object Object],[object Object],[object Object],[object Object],2000’s 80,000 to 110,000 procedures per year ,[object Object],[object Object],[object Object],[object Object]
Current Procedures
Metabolic Syndrome ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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
Diabetes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Prevalence of Diabetes ,[object Object],[object Object]
[object Object],[object Object],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% ,[object Object],[object Object],[object Object],[object Object],Swedish Obese Subject trial (SOS) Prospective matched cohort n = 4,047 pts ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Schauer et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.   Ann Surg. 2003 Oct; 238(4): 467-84   ,[object Object],[object Object],[object Object],[object Object],[object Object]
Biliopancreatic Diversion (BPD) ,[object Object],[object Object],[object Object],[object Object],[object Object],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
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
Clinical Evidence:  Bariatric Surgery & Impact on Metabolic Syndrome
Rates of Remission of Diabetes Adjustable Gastric Banding Roux-en-Y Gastric Bypass Biliopancreatic Diversion >95% (Immediate) 48% (Slow) 84% (Immediate)
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],2002: Antidiabetic Effect of Bariatric Surgery:  Direct or Indirect?
1995-“Who Would Have Though It? Pories et al. Annals of Surgery  ,[object Object],[object Object],[object Object]
Historical Perspective ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Rehfeld J, 2004 1967 – Gastric Bypass DISCOVERY OF GASTROINTESTINAL HORMONES
How Does Bariatric Surgery  Effect glucose homeostasis? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
1. Pathophysiology DIABETES OBESITY ,[object Object],[object Object],[object Object],[object Object],[object Object],INSULIN RESISTANCE INCREASES HEPATIC TRIGLYCERIDE  SYNTHESIS & PRODUCTION OF VLDL LOSS OF VASODILATORY  EFFECT OF INSULIN PRESERVED  SODIUM REABSORPTION HYPERCHOLESTEROLEMIA HYPERTENSION
2. Hormonal Changes after Bariatric Surgery
3. Anti-Incretin Insulin resistance Beta cell depletion Hyperglycemia Too Much Dumping Syndrome Nesidioblastosis Hyperinsulinemia Hypoglycemia Not Enough TYPE 2 DIABETES
GIP and GLP-1 ,[object Object],[object Object],[object Object],… Anti-Incretin ,[object Object],[object Object],[object Object],Anti-incretin
Potential Cure for Diabetes  Hypothesis Hypoglycemia ,[object Object]
Hypothesis ,[object Object]
Hypothesis ,[object Object]
Hypothesis ,[object Object]
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 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
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:
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:
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
[object Object],[object Object],[object Object],[object Object],[object Object],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
Animal Model of DJ Bypass and Glycemic Control ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],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-  Results of DJ Bypass on Glycemic Control ,[object Object],[object Object],[object Object],[object Object],[object Object],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
Leptin??? ,[object Object],[object Object],[object Object],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
Cohen -SAGES 2008
Cohen -SAGES 2008
Cohen -SAGES 2008
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],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.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],March 2008:
Vidal et al. Type 2 Diabetes Mellitus and the Metabolic Syndrome Following Sleeve Gastrectomy in Severely Obese Subjects.  Obes. Surg.  June 2008 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],June 2008
Non-Obese Patients ,[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],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.
DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35.  Surg. Endosc. ,[object Object],[object Object]
CLINICAL TRIAL: Duodenal-Jejeunal Bypass for Type 2 Diabetes (DJBD)  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Dominican Republic 2007 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Lutheran Medical Center Clinical Trial 2008 ,[object Object],[object Object],[object Object],[object Object]
Clinical Trial Eligibility Inclusion Criteria ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Clinical Trial Eligibility Exclusion Criteria ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Preoperative work up ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Operative Course ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Postoperative follow up ,[object Object],[object Object],[object Object],[object Object],[object Object]
Outcomes/Measures ,[object Object],[object Object],[object Object],[object Object]
Clinical Evaluation of the Effect of Duodenal -Jejunal  Bypass on Type 2 Diabetes (June 2007) Patient Demographic, June 6, 2007 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Results ,[object Object],[object Object],[object Object],[object Object],[object Object]
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
Clinical Evaluation of the Effect of Duodenal-Jejunal  Bypass on Type 2 Diabetes ( June 2007) ,[object Object],[object Object],[object Object],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
Clinical Evaluation of the Effect of Duodenal-Jejunal  Bypass on Type 2 Diabetes ( June 2007) ,[object Object],[object Object],[object Object],  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)
!!! ,[object Object],[object Object],[object Object],[object Object]
!!! ,[object Object],[object Object],[object Object],[object Object],[object Object]
!!! ,[object Object],[object Object]
 
SAGES 2008 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis).
Complications ,[object Object],[object Object],[object Object],[object Object],Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis).
Results ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis)
Interim Conclusions ,[object Object],[object Object],[object Object],[object Object]
Interim Conclusions ,[object Object],[object Object]
Interim Conclusions ,[object Object],[object Object],[object Object],[object Object]
Interim Conclusions ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
What The Future Holds? ,[object Object],[object Object],[object Object]
The Surgeon and the Diabetologists
Acknowledgements ,[object Object],[object Object],[object Object],[object Object],[object Object]

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

  • 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. Derived from Center for Disease Control and Prevention website www.cdc.gov Percent of Obese (BMI ≥ 30) in US Adults
  • 3. Derived from Center for Disease Control and Prevention website www.cdc.gov Percent of Obese (BMI ≥ 30) in US Adults
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  • 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.
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  • 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. Clinical Evidence: Bariatric Surgery & Impact on Metabolic Syndrome
  • 15. Rates of Remission of Diabetes Adjustable Gastric Banding Roux-en-Y Gastric Bypass Biliopancreatic Diversion >95% (Immediate) 48% (Slow) 84% (Immediate)
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  • 19. Rehfeld J, 2004 1967 – Gastric Bypass DISCOVERY OF GASTROINTESTINAL HORMONES
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  • 22. 2. Hormonal Changes after Bariatric Surgery
  • 23. 3. Anti-Incretin Insulin resistance Beta cell depletion Hyperglycemia Too Much Dumping Syndrome Nesidioblastosis Hyperinsulinemia Hypoglycemia Not Enough TYPE 2 DIABETES
  • 24.
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  • 29. 2004: Duodenal-Jejunal Exclusion - Foregut
  • 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. 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. 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. 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
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  • 48. DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc.
  • 49. DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc.
  • 50. DePaula AL. et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg. Endosc.
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  • 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
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  • 78. The Surgeon and the Diabetologists
  • 79.

Editor's Notes

  1. Need a better picture
  2. Increased fatty acids also mediate vasoconstricton independently