Comparative Studies and Metabolic Effects of Sleeve Gastrectomy

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Comparative Studies and Metabolic Effects of Sleeve Gastrectomy Alfonso Torquati MD, MSCI Associate Professor of Surgery

Discosures NIH-NIDDK: grant support Covidien: consulting agreement, grant support Allergan: consulting agreement

Body Weight Is Highly Regulated Weight gain Usual weight Weight loss Counter regulation Counter regulation Counter Regulation: Changes in appetite and metabolic rate proportional to the change in body weight work to maintain weight within a set range

Counter Regulation: The Adipostat Brain Body Fat Stores Circulating Signal Caloric Intake

Eat more: Increased food availability calories/person/day has increased 15% since 1970 % of food $ spent outside the home has doubled since 1970 Increased portion size in the 1950 s a 12 oz soda at McDonalds was king-sized; now it s child size Increased energy density (kcal/g) high fat foods; low fat/low cal foods Do less: Obesogenic Environment Increased sedentary leisure time activities TV, computers, video games; cutbacks in mandatory PE Decreased occupational physical activity Increased use of automobiles

Over the next 20 years obesity will be the #1 health problem in the world

The Elusive Magic Pill for Obesity Brain Body Fat Stores Circulating Signal Caloric Intake

Bariatric Mechanisms of Weight Loss The key question is, how does bariatric surgery overcome an individual's adipostatic compensatory mechanisms and maintain significant weight loss? Changes in the entero encefalic endocrine axis may offer part of the explanation. Appetite Control Glucose and Lipid Metabolism Insulin Homeostasis Regulatory Peptides

Objectives To challenge caloric restriction as the only mechanisms of weight loss and comorbidities resolution after the two most common restrictive procedures: Laparoscopic Adjustable Gastric Banding (LAGB) Laparoscopic Sleeve Gastrectomy (LSG) To Review Components Changes of the Entero Encefalic Endocrine Axis (Metabolic Effects) after these procedures.

Laparoscopic adjustable gastric banding (LAGB) A silicon band attached to a subcutaneous port is placed around the proximal stomach Injection of isotonic fluids into the port hydraulically inflates the band Advantages Reversible and adjustable Low operative complication rate Lower risk of gallstones Return to work 1 week after surgery Disadvantages Requires an implanted medical device Easier to cheat Risk of slippage or erosion

LAGB and conventional therapy for T2D: A randomized controlled trial First RCT to compare surgically induced weight loss versus conventional therapy in the management of T2D First RCT to study patients with T2D and obesity Participants: 60 obese patients (BMI 30 40) with recently diagnosed (<2 years) diabetes Outcome measures: Primary: remission of T2D as measured by fasting plasma glucose (FPG) <126 mg/dl and HbA 1c <6.2% Secondary: weight loss and components of the metabolic syndrome Shaded area indicates Position of picture box [1] Dixon et al. JAMA 2008;299:316 23.

Study Design LAGB placed by 1 of 2 surgeons via Pars Flaccida technique Maximise current management Weight loss surgery and conventional therapy for T2D n=30 R Regular review 4 6 weeks Conventional therapy for T2D n=30 Best available medical practice Run-in >3 months 2 years [1] Dixon et al. JAMA 2008;299:316 23.

Loss of excess weight (%) LAGB induces loss of excess weight* 70 60 50 Control group LAGB 40 30 20 10 0 2 years *Excess weight calculated using BMI 25 as the ideal p<0.001 [1] Dixon et al. JAMA 2008;299:316 23.

Patients (%) LAGB induces T2D remission 80 70 60 50 40 30 20 10 0 Control group 2 years LAGB p<0.001 [1] Dixon et al. JAMA 2008;299:316 23.

Dixon: Conclusions Mean HbA 1c and FPG levels were significantly lower in the surgical group at 2 years versus the conventional therapy group (p<0.001) Significant reduction in use of medications for glycemic control in the surgical group compared versus the conventional therapy group at 2 years Significantly fewer subjects had metabolic syndrome in the surgical group (30%) versus the conventional therapy group (87%) at 2 years (p<0.001) The surgical group had a significantly greater improvement in insulin resistance, levels of triglycerides and high-density lipoproteins than the conventional therapy group [1] Dixon et al. JAMA 2008;299:316 23.

Weight control hormones that have been studied after LAGB

Effect of LAGB on Adiponectin Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. Moschen AR et al. Journal of Hepatology, 2009

Effect of LAGB on Leptin Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. Moschen AR et al. Journal of Hepatology, 2009

Effect of LAGB on GLP-1 and GIP Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Korner J et al, SOARD 2007

Effect of LAGB on PYY and Ghrelin Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Korner J et al, International Journal of Obesity, 2009

Summary for LAGB The effect LSG on patients metabolic profile is exerted by caloric restriction and changes in circulating and hepatic levels of Adiponectin and Leptin. LAGB does not induced any significant changes in PYY, Ghrelin, GLP-1, and GIP peptides. LSG is categorized as a restrictive operation, however its metabolic effect clearly extend beyond caloric restriction through changes in adipokine profiles.

Gastric sleeve resection The fundus and body of the stomach are excised, leaving a tube with reduced volume [1] Advantages: [2] Good weight loss No dumping syndrome Disadvantages: [3] Major surgery with associated risks such as staple line bleeding and leakage Increased risk of gallstones [1] Gan S et al. ANZ J Surg 2007;77:958 62. [2] Frezza E. Surg Today 2007;37:275 81. [3] Aggarwal et al. Surg Obes Rel Dis 2007;3:189 94.

Ghrelin Levels after LSG and LAGB Langer et al., Obesity Surgery 2005

Metabolic Changes 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, S; Vagenas, K; Kalfarentzos, F; Alexandrides, T Annals of Surgery. 247(3):401-407, March 2008.

Metabolic Changes after LSG Meal induced changes in ghrelin and PYY levels in 6 patients after LRYGBP (A) and 6 patients after LSG (B). Fasting (black bar) and postprandial (white bar) ghrelin values.

Summary for LSG The effect LSG on patients metabolic profile is exerted primarily by caloric restriction and ghrelins reduction after fundus removal. Meal stimulated PYY is significant higher after LSG however gradually decreases over time, due to physiologic adaptation of the gastric remnant leading to better digestion. Therefore the long-term efficiency of LSG on appetite suppression is under question. LSG is categorized as a restrictive operation, however its ability to extend beyond caloric restriction through changes in gut hormone profiles raises a promise that it will play a leading role in the future of bariatric surgery.