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

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

  • 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
    • National Hospital Discharge Survey Public-use data file and documentation. Multi-year data CD-ROM. National Center for Health Statistics, 1979-1996.
    • Nguyen et al. Accelerated growth of bariatric surgery with the introduction of minimally invasive surgery. Arch Surg 2005; 140: 1198-202.
    • Griffen et al. The decline and fall of the jejunoileal bypass. Surg Gynecol Obstet 1983; 157: 301-8.
    • Shirmer et al. Bariatric Surgery Training: Getting Your Ticket Punched. J Gastrointest Surg 2007;11: 807-12.
    Popularity of Surgical Management Period or Decades Incidence of Surgery Reason for Change Late 1970’s Early 1980’s 25,000 procedures per year
    • Innovative procedures
    • gastroplasty
    • loop GBP
    • jejuno-ileal bypass
    Late 1980’s 1990’s 5,000 procedures per year
    • Multifactorial:
    • High M&M
    • Ineffective long-term
    • Perceived failure
    • Surgeon experience
    2000’s 80,000 to 110,000 procedures per year
    • Multifactorial:
    • Laparoscopy
    • Long-term data
    • Centers of Excellence
  • Current Procedures
  • Metabolic Syndrome
    • Also Known as:
    • 1. Syndrome “X”
    • 2. Insulin Resistance Syndrome
    • 3. Reaven’s Syndrome
    • 4. Deadly Quartet
    • 5. CHAOS
    • C oronary Artery Disease
    • H ypertension
    • A dult Onset Diabetes
    • O besity
    • S troke
  • 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
    • Considered major public health problem – emerging as a world wide pandemic. In 1995 ~ 135 million people worldwide
    • Expected to rise to close to 300 million by 2025
    • CDC (2008) cases of diabetes have increased to 15% in just the past two years
    • 1998-Annual direct health care cost was estimated to be $60 billion in US
    • Complications
      • Peripheral vascular disease (PVD) accounts for 20-30%
      • 10% of cerebral vascular accident
      • Cardiovascular disease accounts for 50% of total mortality
      • 1. Venkat et al Diabetes–a common, growing, serious, costly, and potentially preventable public health problem. Diabetes Res
      • Clin Pract. 2000; 5 (Suppl2): S77–S784.
      • 2. H. King et Global burden of diabetes, 1995-2025: prevalence, numerical estimates and projections. Diabetes Care 21 (1998)
      • 1414-1431.
      • 3. CDC website @ www.CDC.com
  • Prevalence of Diabetes
    • 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
    • Annual number (in thousands) of new cases of diagnosed diabetes among adults aged 18-79 years, United States, 1980–2005
    • 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.
    • 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.
    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%
    • Resolution of:
    • Diabetes: 70%
    • HTN: 62%
    • Sleep apnea: 86%
    Swedish Obese Subject trial (SOS) Prospective matched cohort n = 4,047 pts
    • At 10 years:
    • Med: 1.6% gain
    • Surg: 16% loss
    • Improved by surgery:
    • Diabetes
    • Lipid profile
    • HTN
    • Hyperuricemia
  • Schauer et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003 Oct; 238(4): 467-84
    • 1160 patients underwent LRYGBP 5-year period
    • LRYGBP resulted in significant weight loss (60% percent of excess body weight loss) and resolution (83%) of T2DM
    • Fasting plasma glucose and HBA1C normalized (83%) or markedly improved (17%) in all patients
    • Patients with the shortest duration and mildest form of T2DM had a higher rate of T2DM resolution after surgery
      • suggesting that early surgical intervention is warranted to increase the likelihood of rendering patients euglycemic
  • Biliopancreatic Diversion (BPD)
    • 312 BPD, obese patients with type 2 DM were followed for pre and postoperative serum glucose, triglycerides, cholesterol & arterial pressure measurements
    • After BPD, fasting serum glucose fell within normal values in 310 patients; remained normal up to 10 years in all but 6 patients
    • Evidence of hypertension disappeared in majority of patients
    • Glycemic control translates into a reduced mortality for these patients as well as a low frequency of death from cardiovascular events
    • TRUE CLINICAL RECOVERY
    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)
    • “ Gastric bypass and biliopancreatic diversion
    • seem to achieve control of diabetes as a primary and
    • independent effect, not secondary
    • to the treatment of overweight.”
    • Potential of Surgery for Curing Type 2 Diabetes Mellitus. Rubino, Francesco, MD; Gagner,
    • Michel MD, FACS, FRCSC Annals of Surgery; 236 (5): 554-559, November 2002
    2002: Antidiabetic Effect of Bariatric Surgery: Direct or Indirect?
  • 1995-“Who Would Have Though It? Pories et al. Annals of Surgery
    • NIDDM is no longer an uncontrollable disease
    • The correction on NIDDM occurs within days following gastric bypass, long before significant weight loss has occurred
    • Decrease caloric intake and changes in incretin stimulation of the islets by the gut may play a role
  • Historical Perspective
    • 1955- Friedman
      • 3 patients with poorly control DM
      • 3-4 days after subtotal gastrectomy all 3 pateints showed an improvement in their DM
        • Occurred sooner than associated weight loss
        • Patients later regained their weight without an associated loss of glucose control or glycosuria
    • Mingrone 1977 : Case report
      • Young, non obese woman with DM who underwent BPD for chylomicronemia
      • Plasma insulin and blood glucose levels normalized within 3 months
    • Bittner –1981- subtotal gastrectomy and gastrointestinal reconstructions that excluded duodenal passage (B2 and RYGB
      • Lowered plasma glucose and insulin
      • Conclusion: Plasma glucose and insulin fall rapidly post-operatively
        • antidiabetic medications can be reduced or stopped shortly after gastrointestinal bypass interventions
      • Rubino F. Bariatric Surgery:effects on glucose homeostasis. Curr. Opin. Clin. Nutr. Metab. Care 9: 497-507
      • Bittner R. Homeostasis of glucose and gastric resection: the influence of food passage through the duodenum Z Gastroenterology 1981; 19: 698-707.
      • Friedman NM et al. The amelioration of diabetes mellitus following subtotal gastrectomy. Surg. Gynecol. Obstetr. 1955; 100:201-204
  • Rehfeld J, 2004 1967 – Gastric Bypass DISCOVERY OF GASTROINTESTINAL HORMONES
  • How Does Bariatric Surgery Effect glucose homeostasis?
    • Intestinal Malabsorption?
      • Weight loss reduces insulin resistance
      • Glucose malabsorption reduces stress on islet cells
      • Fat malabsorption reduces circulating free fatty acids and improves insulin sensitivity
    • Hormonal Changes?
      • Re-routing of food alters the dynamic of gut-hormone secretion
        • Decrease in plasma levels of leptin & insulin
        • Increased levels of adiponectin & peptide YY3-36
        • Increased levels of glucagon-like peptide 1 (GLP-1)
    • Rearrangement of GI anatomy?
        • “ Hindgut hypothesis”
        • “ Foregut hypothesis”
  • 1. Pathophysiology DIABETES OBESITY
        • Excess adipose tissue increases
        • available triglyceride stores
        • Breakdown of TG leads to overabundance
        • of circulating fatty acids
        • INCREASED FATTY ACIDS
    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
    • Stimulated by enteral nutrients
    • insulin secretion / action
    •  -cell proliferation
    … Anti-Incretin
    • Stimulated by enteral nutrients
    • insulin secretion / action
    •  -cell proliferation
    Anti-incretin
  • Potential Cure for Diabetes Hypothesis Hypoglycemia
        • Rubino et al; Ann. Surg. 2002
  • Hypothesis
        • Rubino et al; Ann. Surg. 2002
  • Hypothesis
        • Rubino et al; Ann. Surg. 2002
  • Hypothesis
        • Rubino et al; Ann. Surg. 2002
  • 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
    • Bariatric Surgery clearly has an antidiabetic effect; thought to be secondary to surgically induced weight loss and decreased caloric intake
    • But, how do we explain the finding that glycemic control occurs within days, before significant weight loss has been achieved???
      • Direct effect of the surgical bypass of proximal intestines
      • Hormonal Regulation of Glucose Metabolism
        • Insulin, glucagons-like peptide (GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon and leptin
    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
    • Animal Model of non-obese type 2 diabetes; Goto-Kakizaki rats
    • Twelve (12-14 wk old) rats randomly underwent
    • gastrojejeunal bypass or no intervention
    • * All fed with same type of diet
    • * All fed with same amount of diet
    • * Pre-op, post-op 1 wk & 1 month
    • weight assessment & fasting glycemia
    • * Oral Glucose Tolerance Test performed at each
    • time point
    • * Hormone levels were measured after 20 minutes of oral
    • overload
    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
    • Group 1 and Group 2 rats remained the same weight during the experiment
    • OGTT improved in DJ bypass group
    • Glucose levels were better at 1 week & 1 month after DJ bypass in all times of OGTT (basal, 10 min, 120 min)
    • Post-oral glucose load levels of glucagon, insulin, GLP-1 and GIP remained unchanged in both groups
    • In DJ bypass group there is a significant decrease in leptin levels noted
    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???
    • Adipocyte-derived hormone
    • In mice, leptin acts as a hormonal signal on the afferent limb of a negative feedback loop between the adipose tissue and hypothalmic centers
    • Physiological increase in plasma leptin has been shown to significantly inhibit glucose-stimulated insulin secretion in vivo and to determine insulin resistance
    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
      • Double blind study: 16 patients assigned to LRYGBP and 16 Pts to LSG
      • Patients reevaluated on the 1st, 3rd, 6th, and 12th mos
      • Results:
        • No change in ghrelin levels after LRYGBP Significant decrease in ghrelin after LSG ( P < 0.0001)
        • Fasting PYY levels increased after either surgical procedure ( P <= 0.001)
        • Appetite decreased in both groups but to a greater extend after LSG
    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.
    • “ PYY levels increased similarly after either procedure.
    • The markedly reduced ghrelin levels in addition to increased
    • PYY levels after LSG, are associated with greater appetite
    • suppression and excess weight loss compared with LRYGBP”
    • March 2008: 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.
    March 2008:
  • Vidal et al. Type 2 Diabetes Mellitus and the Metabolic Syndrome Following Sleeve Gastrectomy in Severely Obese Subjects. Obes. Surg. June 2008
    • 12 mos prospective study 9 severely obese T2DM patients LSG (SG; n = 39) or LRYGP (GBP; n = 52)
    • Matched for DM duration, type of DM treatment, and glycemic control
    • Results
      • T2DM resolved 84.6% SG and (84.6%) GBP (p = 0.618)
      • Weight loss was not associated with T2DM resolution after SG or GBP
      • Shorter DM duration and DM treatment and glycemic control associated with both groups
    • SG is as effective as GBP in inducing remission
    • of T2DM and the MS.
    • 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
    • Type 2 Diabetes Mellitus and the Metabolic Syndrome Following Sleeve Gastrectomy in Severely Obese
    • Subjects. Obes. Surg. 2008, Vidal et al
    June 2008
  • Non-Obese Patients
    • Slides taken from: DIABETES IS NO LONGER A HOPELESS DISEASE The Guilty Gut,Walter Pories, MD, FACS
    • First Clinical description of laparoscopic stomach-preserving DJB for treatment of T2DM
    • 2 patients with >12 mos f/u (13/15 mos)
    • By 5 th week of surgery, both patients were euglycemic and free of all antidiabetic medications
    • Conclusion:
      • LDJB is a feasible and safe
      • could represent valuable therapeutic option
    • 39 patients underwent laparoscopic ileal interposition into proximal jejunum via sleeve or diverted sleeve gastrectomy
      • BMI < 35
      • All had type II DM for at least 3 years
        • Mean operative time was 185 minutes
        • Mean post-op follow up was 7 months
    • 87% of patients discontinued preop oral hypoglycemics, insulin or both
    • Hemoglobin A1c decreased from 8.8% to 6.3%
    • All but one patient experienced normalization of cholesterol
    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.
    • Conclusion:
      • 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
  • CLINICAL TRIAL: Duodenal-Jejeunal Bypass for Type 2 Diabetes (DJBD)
    • SUMMARY:
    • Clinical Evaluation of the Effect of Duodenal-Jejunal Bypass on Type 2 Diabetes
    • FACILITY:
    • Center for Advance Medicine
    • Santo Domingo, Dominican Republic
    • STUDY OFFICIALS/INVESTIGATORS:
    • George Ferzli, MD, FACS - Study Principal Investigator,
    • SUNY Downstate, Brooklyn, New York, USA
    • Abel Gonzalez, MD - Center for Advanced Medicine,
    • Santo Domingo, Dominican Republic
    • Martin Bluth, MD, PhD - Director of Research, Assistant Professor,
    • Departments of Surgery and Pathology, Brooklyn, NY USA)
  • Dominican Republic 2007
    • Prospective controlled clinical trial
    • Seeking to recruit total of 50 patients
    • www. clinicaltrials .gov
    • Unique Protocol ID: AS07006
    • Clinicaltrials.gov ID: NCT00487526 .
  • Lutheran Medical Center Clinical Trial 2008
    • Prospective study
    • Seeking to recruit total of 50 patients
    • www. clinicaltrials .gov
    • ID: NCT00694278, LMC 95
  • Clinical Trial Eligibility Inclusion Criteria
    • Adults age 20-65
    • Clinical diagnosis of type II diabetes:
      • a) A normal or high C-peptide level (to exclude type 1 diabetes) (>.9ng/ml)
      • b) A random plasma glucose of 200mg/dl or more with typical symptoms of diabetes
      • c)A fasting plasma glucose of 126mg/dl or more on more than one occasion
    • BMI 22-34 KG/m2,
    • Patients on oral hypoglycemic medications or insulin to control T2DM Inadequate control of diabetes as defined as HbA1c>7.5
    • No contraindications for surgery or general anesthesia
    • Ability to understand and describe the mechanism of action and risks and benefits of the operation
  • Clinical Trial Eligibility Exclusion Criteria
    • Diagnosis of type 1 diabetes
    • Planned pregnancy within 2 years of entry into the study
    • Previous gastric or esophageal surgery, immunosuppressive drugs including corticosteroids, coagulopathy, anemia, any contraindication to laparoscopic gastric bypass or medical hypoglycemic therapy
    • Severe concurrent illness likely to limit life (e.g. cancer) or requiring extensive disorder (e.g. pancreatic insufficiency, Celiac sprue, or Crohn’s disease)
    • Pre-existing major complications of diabetes, significant proteinuria (>250mg/dl), severe proliferate retinopathy, severe neuropathy or clinical diagnosis of gastropathy
    • MI in the previous year
    • Unable to comply with study requirements, follow-up or give verbal consent
    • Liver cirrhosis
    • Previous abdominal surgery
  • Preoperative work up
    • Detailed informed consent explain to patient and
    • Baseline assessment by multidisciplinary surgical team
      • Surgeon, primary physician, endocrinologist, cardiologist, gastroenterologist, psychiatrist, nutritionist
    • Routine work-up and blood work
      • (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. )
    • Studies
      • Electrocardiogram (ECG), chest radiograph, and Esophagogastroduodenoscopy (EGD), PFT’S (if indicated)
  • Operative Course
    • Laparoscopic Duodenal-Jejunal bypass under GETA
    • Preoperative prophylaxis antibiotic (Ancef or Clinda in PCN allergy)
    • Sequential compression devices for deep venous thrombosis (DVT) prophylaxis in addition to LMWH (5,000units SQ).
    • Operative/Intraoperative data
      • OR time, EBL, complications, unusual findings
    • NPO until upper gastrointestinal (UGI) on POD#1
    • Clear fluids are begun following the UGI study, and continue for 5-7 days
    • Patient follow up with nutritionist for dietary guidelines
  • Postoperative follow up
    • Follow up with multidisciplinary team
      • 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
    • 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
    • Nutritionist follow up – continue to puree diet
    • Attend support group
  • Outcomes/Measures
    • The primary outcome
      • Reversion of hyperglycemia to euglycemia (normalization of HbA 1c to <7%)
    • Secondary outcomes
      • - lipid profiles, and C-peptide
  • Clinical Evaluation of the Effect of Duodenal -Jejunal Bypass on Type 2 Diabetes (June 2007) Patient Demographic, June 6, 2007
    • LDJB was performed successfully in 7 patients
    • Mean age of 43.3 range (33-52)
    • Limb was 75cm/75cm
    • Operative time average 98 min
    • Length of stay 3 days
  • Results
    • Overall, no complications were observed that in any way stemmed from the procedure
    • One patient developed a liver abscess
      • required drainage unrelated to the procedure
    • All patients consistently felt relief from their preoperative symptoms.
    • No deaths
  • 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)
    • HBA1c, Fasting Blood Glucose (FBG), Triglycerides (TG), Cholesterol (Chol) and C-peptide (Cpep) were measured at pre-op and 1 year
    • 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.
    • 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.
    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)
    • The mean HBA1c at pre-op and 1 year was 9.371 and 8.500 respectively
    • FBG at pre-op and 1 year were 208 and 154 respectively for the seven patients (p=0.057)
    • Lipid profiles improved with lower total cholesterol levels and triglycerides 1 year
      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)
  • !!!
    • One patient required insulin preop, at 6 months she was no longer on insulin and all lab work was normal
    • She became pregnant at 6 months following surgery
    • Her diabetes returned and her insulin requirement is at the pre-op level
    • 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
  • !!!
    • Our Study- 1 year follow-up
    • 5 patients (71%) T2DM > 10 years (10-19)
    • 1 pre oral/insulin-free from medication at 1 yr
    • 2 required less dosages
    • All 5 patients –no symptoms and improved state of health
  • !!!
    • 2 patients with c-peptide <1, the HbA1c increased following the procedure
    • Both patients had decreased in medication requirements
  •  
  • SAGES 2008
    • 35 patients T2DM for 2-10 years l underwent LDJB
    • April-Nov 07
    • 15 women, 20 men
    • Comorbidities
      • 75% with HTN
      • 58% Hypercholesteremia
      • 62.5% Hypertriglyceremia
    • Mean OR time = 46 minutes (33-78 min)
    • Hospital stay 30 hrs –81 days
    • PPI for 90 days
    • Patients kept on metformin/glimeperide (metformin withdrawn when HBA1c <6)
    Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis).
  • Complications
    • 1 death
    • 2 intestinal obstruction
    • 1 pos-operative pancreatitis
    • 2 intracavitary bleeding
    Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis).
  • Results
    • HbA1c decreasing from 8.9 to 6.1 and 72.3%
    • 72.3% of patients had control of their hypertension: reduced sympathetic outflow?
    • 13/35 patients reported food intolerance: 8/13 required admission (no women)
    • Oral Ginger and sildenafil are very helpful
    • 75% complained of post-prandial sleepiness
      • These side effects may be attributed to gastroparesis and the postulated diminished sympathetic outflow, a result of central leptin suppression and duodenal bypass
    Cohen, Duodenojejunal bypass for the treatment of T2DM in patients with BMI from 22 to 34. (Nevis)
  • Interim Conclusions
    • Very promising initial experience.
    • The vast majority of insulin users do not use it anymore very early in the post-op.
    • 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.
    • In patients with higher BMIs, but still under 35 (32-35), it seems that major weight loss is needed to achieve control of T2DM.
  • Interim Conclusions
    • What are the correct inclusion/exclusion criteria? Should we cut off at 8, 9, 10 years?
    • Time of T2DM history does not seem important, but C peptide below 1 YES!!!
  • Interim Conclusions
    • Don ’t rush to withdraw medication.
    • We add an incretin effect, but METFORMIN helps to decrease hepatic defective glucose production.
    • What is the antidiabetes mechanism?
    • Cold pressor test before and after duodenal exclusion to assess sympathetic response ?
  • Interim Conclusions
    • What are the appropriate limb lengths? 50/80?
    • Is it necessary to bypass the entire duodenum?
      • If yes, how can we assess that?
      • Does it make any difference?
    • Do we need complex operations in this subset of patients?
      • Are the mortality/ complication rates reasonable?
    • Will an added sleeve gastrectomy in selected patients be needed to avoid gastroparesis, mainly in those with BMI>32?
      • Or is a LRYGB more adequate?
  • What The Future Holds?
    • Zhou et al. In vivo reprogramming of adult pancreatic cells to B-cells. Nature. October 2008
    • Transcription factors Ngn3, Pdx1 and Mafa reprograms differentiated pancreatic cells in adult mice into cells that closely resemble Beta cells…
    • Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard University.
  • The Surgeon and the Diabetologists
  • Acknowledgements
    • Kell Juliard
    • Martin Bluth, MD, PhD
    • Giancarlo Cires, MD
    • Rosemarie E Hardin, MD
    • Joel Ricci, MD