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Resolution of Metabolic Syndrome and Morbid Obesity Surgery

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  • So why is it important to us??? Take a look at the prevalence of metabolic syndrome in the United States population; great market for surgeons for treatment of metabolic syndrome with bypass procedures
  • Reported as high as 67% in the 60-69 year old population
  • The pathophysiology of metabolic syndrome is very complex and not fully elucidated; however, you can easily see that there is significant interplay between hormonal signals and metabolic mediators resulting in the classic constellation of symptoms
  • Increased fatty acids also mediate vasoconstricton independently
  • Dr.Ferzli, please add a few words about your expereince in the Dominican Rebuplic and early results!
  • Transcript

    • 1. Resolution of Metabolic Syndrome & Morbid Obesity Surgery George S.Ferzli, M.D., Benjamin Chandler, Giancarlo Cires, M.D. , Rosemarie E.Hardin, M.D Metabolic Surgery Symposium New Mexico, 2007
    • 2. 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
    • 3. History 1947: Dr.Jean Vague; made observation that upper body obesity predisposed to diabetes, Atherosclerosis, gout and calculi 1967: Avogaro & Crepaldi; described 6 moderately obese patients with diabetes hypercholesterolemia and marked triglyceridemia, all of which improved with a Hypocaloric, low carbohydrate diet In 1977: Haller used the term “ metabolic syndrome ”: obesity, diabetes mellitus, hyperlipoproteinemia, hyperuricemia and steatosis hepatitis when describing the additive effects of risk factors on atherosclerosis In 1977: Gerald B. Phillips; developed the concept that Risk factors for myocardial infarction concur to form a “constellation of abnormalities” : glucose intolerance, hyperinsulinemia, hyperlipidemia and hypertension is associated with heart disease and obesity MUST BE LINKING FACTOR 1988: Gerald M. Reaven proposed insulin resistance as the linking factor and named the constellation of abnormalities Syndrome X X
    • 4. Prevalence
    • 5. Signs & Symptoms
      • Fasting hyperglycemia
      • Hypertension
      • Central obesity / “apple-shaped adiposity”
      • Decreased HDL cholesterol
      • Elevated triglycerides
      • Elevated uric acid levels
    • 6. Definition
      • World Health Organization (WHO):
        • Requires presence of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance and two or the following:
          • Blood pressure > 140/90
          • Dyslipidemia: Triglycerides > 1.695 mmol/L, HDL<0.9mmol/L (male) and <1.0 (female)
          • Central obesity: waist:hip ratio > 0.90(male), >0.85(female) and/or body mass index >30 kg/m 2
          • microalbuminuria
    • 7. Definition
      • European Group for the Study of Insulin Resistance (EGIR)
        • Requires insulin resistance and two or more of the following :
          • Central obesity: waist circumference >94 cm (male), >80 cm (female)
          • Dyslipidemia: TG > 2.0 mmol/L or HDL < 1.0 mg/dl
          • Hypertension >140/90 mmHg
          • Fasting plasma glucose > 6.1 mmol/L
    • 8. Definition
      • National Cholesterol Education Program (NCEP):
        • Requires at least three of the following:
          • Central obesity: waist circumference >102 cm or 40 inches (male), >88 cm or 36 inches (female)
          • Dyslipidemia: TG >1.695 mmol/L (150 mg/dl)
          • HDL < 40 mg/dl (male), <50 mg/dl (female)
          • Blood pressure > 130/85 mmHg
          • Fasting plasma glucose >6.1 mmol (110 mg/dl)
    • 9. Definition
      • American Heart Association
        • Elevated waist circumference: men > 40 inches (102 cm); women > 35 inches (88 cm)
        • Elevated triglycerides: > 150 mg/dl
        • Reduced HDL cholesterol: men< 40 mg/dl, women <50 mg/dl
        • Elevated blood pressure: 130/85 mmHg
        • Elevated fasting glucose: >100 mg/dl
    • 10. Etiology
      • Aging ( more prevalent with increasing age)
      • Genetics
      • Lifestyle (physical inactivity and increased caloric intake)
      • Systemic inflammation: inceased inflammatory markers (i.e. C-reactive protein, fibrinogen, interleukin-6 & TNF alpha)
    • 11. Pathophysiology
    • 12. 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
    • 13. Therapy
      • First Line treatment: Lifestyle modification
        • Caloric restriction
        • Increased physical activity
      • Drug treatment is often required
        • Diuretics and ACE inhibitors for HTN
        • Statin drugs to lower cholesterol
        • Use of drugs that decrease insulin resistance i.e. metformin and thiazolidinediones is controversial and not FDA approved
      SURGERY
    • 14. BENEFITS OF SURGERY
    • 15. Options
      • Both procedures result in effective weight loss and resolution of Type 2 DM in obese patients
      • Both result in normal plasma and insulin concentrations
      • Both result in restoration of normal B -cell response to hyperglycemia
      • Both may be the “next step” in solving the mystery of metabolic syndrome
      Roux-en-Y Gastric Bypass (RYGB ) Biliopancreatic Diversion (BPD )
    • 16. Hormonal Changes after Bariatric Surgery
    • 17. Metabolic Effects of Bariatric Surgery
    • 18. Clinical Evidence: Bariatric Surgery & Impact on Metabolic Syndrome
    • 19. EFFECT?
    • 20. Resolution of diabetes mellitus and metabolic syndrome following Roux-en-Y gastric bypass and a variant of biliopancreatic diversion in patients with morbid obesity. Alexandrides TK , Skroubis G , Kalfarentzos F . Endocrine Division, Department of Internal Medicine, School of Medicine, University of Patras, Greece
      • The objective of this study was to investigate the effects of RYGBP and BPD-RYGBP, a variant of BPD with a lower rate of metabolic deficiencies than BPD, on DM2 and the major components of metabolic syndrome in patients with morbid obesity and DM2.
      • METHODS : The prospective database of our unit, from June 1994 until May 2006, was analyzed and 137 patients with DM2 were found. 26 underwent RYGBP (BMI 46.1 +/- 2.9 kg/m2) and 111 BPD-RYGBP (BMI 59.7 +/- 10.6 kg/m2). 7 of the patients were on insulin (4.90%) and 37 on oral hypoglycemic agents (25.87%). Pre- and postoperative medications, and clinical and biochemical parameters were considered in the analysis. The mean
      • follow-up was 26.39 +/- 21.17 months.
      • RESULTS : Excess weight loss was approximately 70% after either procedure. DM2 resolved in 89% and 99% of the cases following RYGBP and BPD-RYGBP, respectively. 2 years after BPD-RYGBP all the patients had blood glucose < 110 mg/dl, 95% had normal cholesterol, 92% normal triglycerides and 82% normal blood pressure. The respective values following RYGBP were 66%, 33%, 78% and 44%. Uric acid decreased significantly only after BPD-RYGBP. Liver enzymes improved in both groups.
      • CONCLUSIONS: RYGBP and BPD-RYGBP are safe and lead to normalization of blood glucose, lipids, uric acid, liver enzymes and arterial pressure in the majority of patients, although this variant of BPD was more effective than RYGBP. We suggest that further studies should also investigate its usefulness in patients with milder degrees of obesity, DM2 and metabolic syndrome.
      Obes Surg. 2007 Feb;17(2):176-84.
    • 21. Roux-en-Y Gastric Bypass
      • Changes in GI hormones have been proposed to contribute to the restoration of euglycemia after RYGB
      • Bypass of the duodenum and proximal jejunum and rapid passage of food from stomach to distal ileum augment the secretion of GLP-1
      • GLP-1 potently increases insulin secretion and possibly insulin sensitivity.
    • 22. Roux-en-Y Gastric Bypass Prospective Study : enrolled 36 obese patients prior to undergoing Roux-en-Y gastric bypass compared to age and sex matched controls Fasting glucose, HDL cholesterol, triglyceride level, BP, waist circumference & inflammatory markers were measured pre-op, 6wks post op & 52 weeks post op
    • 23. Roux-en-Y Gastric Bypass
    • 24. Biliopancreatic Diversion (BPD)
      • BPD limits fat and starch absorption while preserving the intestinal absorption of protein and non caloric essential aliments
      • It is hypothesized that the increased free fatty acid oxidation that occurs in obese patients inhibits glucose oxidation, thus causing insulin resistance
      • Reduced fat absorption should result in enhanced insulin sensitivity
      • Lipid deprivation selectively reduces intra myocellular lipid stores; improving the action of insulin and intracellular insulin signaling
      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
    • 25. 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
    • 26. 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
    • 27. Madan AK, Orth W, Ternovits CA et al. Metabolic Syndrome: yet another co-morbidity gastric bypass helps cure. Surgery for Obesity&Related Diseases. Jan 2006; 2 (1):48-51
      • Retrospective Study ( n=53 )
      • Chart review of all patients undergoing laparoscopic gastric bypass surgery during a 6 month period performed to identify patients with
      • pre-op diagnosis of metabolic syndrome (using NCEP guidelines)
      • 32/53 (60%) pts had metabolic syndrome
      • No difference in pre-op body mass index between patients who had metabolic syndrome (47.4 kg/m 2 )and those who did not (49.8 kg/m 2 )
      • The percentage of excess body weight lost after one year was 78% in patients with metabolic syndrome
      • Post-operatively, 1/53 (2%) patients had metabolic syndrome (P<.0001)
    • 28. FUTURE ??
      • Increasing evidence demonstrates excellent glycemic control and resolution of metabolic syndrome in obese patients following gastric bypass procedures
      • Similar findings also evident in early experience with non-obese individuals with poor glycemic control or Type 2 D
      • Is Type 2 Diabetes a potential “surgical disease” cured by bariatric surgery???
      YES
    • 29. Questions????

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