Obesity, Metabolic Syndrome, and Bariatric Surgery

Jon Gabrielsen MD, FACS Minimally Invasive/Bariatric Surgery Geisinger Medical Center

Objectives

• Identify scope of the obesity epidemic • Understand the anatomy of the most common weight loss operations • Understand the results bariatric surgery • Identify common post-operative problems • Understand nutritional needs of bariatric patients after surgery • Understand the effect of bariatric surgery hormonally and potential mechanisms of diabetes resolution

Obesity Trends in the US

• 1960-2000 Obesity prevalence increased from 13.3% to 30.9% • 1991-Only 4 states have obesity rates 15% or higher • 2000-Every state except Colorado has a rate of 15% or higher • 22 states have rates of 20% or more

Surg Clin N Amer 88(2008); 991-1007 Bariatric Surgery: Choosing the Optimal Procedure

Obesity Trends* Among U.S. Adults BRFSS, 1990, 1999, 2008 (*BMI



30, or about 30 lbs. overweight for 5’4” person) 1990 1999 2008 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Definition of obesity Body Mass Index (BMI) = kg/m 2 22- 25 = normal 25- 29 = overweight 30- 40 = obese > 40 = morbidly obese > 50 = super obese

Obesity and Life Expectancy

• BMI >30 associated with 50-100% increased risk of death from all caused compared to BMI <25 • Caucasian men 20-30 yrs old with BMI > 45 may lose 13 years of life expectancy • Caucasian women 20-30 yrs old with BMI > 45 may lose 8 years of life expectancy • African American men 20-30 yrs old with BMI > 45 may lose 20 years of life expectancy • African American women 20-30 yrs old with BMI > 45 may lose 5 years of life expectancy

Surg Clin N Amer 88(2008); 991-1007 Bariatric Surgery: Choosing the Optimal Procedure

•

Adipokines-Endocrine Function of Adipose Tissue

Leptin (from Grk leptos-

thin

) – White adipose tissue is richest source – 25% of blood leptin from stomach (fundic pepsinogen secreting cells) – Signals the brain (when suppressed) that the body is starving – In the absence of leptin, the brain senses starvation despite massive obesity • Obese patients have impairment in leptin signaling to hypothalamus • Individuals lacking leptin have little or no satiety in response to meals • Leptin modulates other meal related hormone changes

Adipokines-Endocrine Function of Adipose Tissue

• Adiponectin – Secreted in inverse relation to total body mass of fat – Low levels implicated in insulin resistance – Weight loss increases adiponectin levels

Adipokines-Endocrine Function of Adipose Tissue

• Inflammatory mediators (TNF-alpha, IL-6) – Produced by adipose tissue proportionally to total body mass of fat – Impair insulin signal transduction in muscle and liver (promote activation of serine kinases rather than tyrosine kinases) – Exercise turns IL-6 from a pro-inflammatory cytokine to an anti-inflammatory cytokine

Etiology of Metabolic Syndrome

• Insulin-main anabolic and anticatabolic hormone – Stimulates glucose, protein, and lipid metabolism as well as RNA and DNA synthesis – Modifies enzymatic activity and transport processes within the cell • Stimulated by blood glucose and AA • Response is modulated by GI hormones called incretins

Etiology of Metabolic Syndrome

• Obesity leads to interruption/impairment of the signaling cascade-impaired glucose transport • Compensatory hyperinsulinemia • Overexpression of insulin action in tissues with normal or minimally impaired insulin sensitivity – Acanthosis Nigricans – Increased thickness of skin

Progression to DM II

• Decrease in early meal-mediated insulin secretion – Exaggerated rise in plasma glucose following meal – Prolongation of post-parandial rise • Progressive loss of insulin secretion in response to nutrients – 2 hour PP glucose rises from 140 to 200 mg/dl with time – Progressive loss of beta cell function • At time of clinical diagnosis beta cell function is 50% of normal – Drops 50% each subsequent 6 years – After 10-15 years most patients need insulin

Metabolic Syndrome

• International Diabetes Federation – Central Obesity (cutoff is based on ethnicity) – Any two of the following • TG >150 mg/dL • HDL C <40 mg/dL (M), <50 mg/dL (F) • Blood Pressure >130 sys or >85 diastolic • Plasma glc >100 mg/dL or diagnosed DM II

History of Bariatric Surgery • 1970’s • 1970 -1991 •

1991

• 1990’s • 2000 Initial operations “Experimental therapy”

NIH Consensus Conference

Laparoscopy Centers of Excellence

NIH Bariatric Criteria 1. BMI >40 or BMI > 35 with co-morbidities such as diabetes or sleep apnea 2.

“Reasonable attempts”(6 months) of a comprehensive medical program 3. No procedure specified

Bariatric Procedures: Categories

• Restrictive – Vertical Banded Gastroplasty – Laparoscopic Adjustable Banded Gastroplasty – Laparoscopic Sleeve Gastrectomy* • Malabsorptive/Restrictive – Roux-en-Y Gastric Bypass – Biliopancreatic Diversion with Duodenal Switch (BPD-DS)

Bariatric Surgery: Definitions Restriction Satiety

Bariatric Surgery: Definitions Malabsorption Calorie deficit Micronutrient deficit

Vertical Banded Gastroplasty

Stomach Food Passage Nutritional Issues Weight Loss

Small Normal None Modest

Failure Rate

High

Vertical Banded Gastroplasty 80% Failure after 10 years - staple line breakdown - weight regain - stenosis Balsiger et al.

J. GI Surgery

, 2000

Laparoscopic Gastric Band

Laparoscopic Gastric Band

Stomach Food Passage Nutritional Issues Weight Loss Failure Rate

Small Normal None Modest, Slow High

Technique

Easier

Laparoscopic Adjustable Gastric Banding

• Common complications – Inadequate weight loss – Device related complications – Heartburn – Dysphagia – Esophageal Motility Problems – Slippage of Band – Erosion of Band

Laparoscopic Sleeve Gastrectomy

Stomach Food Passage Nutritional Issues Weight Loss Failure Rate Technique

Long and Narrow Normal None Good/Relatively Rapid Low to Moderate Moderate Degree of Difficulty

Laparoscopic Sleeve Gastrectomy

• Long term data still lacking • May require addition of malabsoptive procedure (RYGB or BPD-DS) • GERD-tends to show up long after the operation • Stricture • Leak

Roux en Y Gastric Bypass

Stomach Food Passage

Small Bypass lower stomach and small bowel

Nutritional Issues

MVI, Fe, Ca, B12

Weight Loss Failure Rate Technique

Excellent, Rapid Low Complex

BPD-DS

Stomach Failure Rate

Long and Narrow

Food Passage Nutritional Issues Weight Loss

Bypass lower stomach and much of small bowel MVI, Fe (Anemia), Ca (Metabolic Bone Disease, B12, Fat Soluble Vitamins Excellent, Rapid Low

Technique

Complex

Biliary Pancreatic Bypass Sleeve Gastrectomy

BPD/DS

• Duodenal Switch (1986 Hess)-modification of BPD – 80% weight loss at 18 months – Excellent long term results with Lap BPD/DS (Marceau et. al) • 82% of patients achieve >50% EBWL • Mean 73% • BMI <50, 92% achieve >50% EBWL, 83% if BMI >50 • Discontinuation of diabetic meds in 92% • Off CPA in 90%

RYGB/BPD-DS Complications

• Early – Leak – Ulceration/Stricture – Obstruction – Bleeding – Dehydration • Late – Nutritional deficiencies – Internal and abdominal wall hernias – Stricture/Ulcer

Outcomes: Mortality • Mortality at 5 years – Bariatric surgery • includes peri-op mortality 0.4% 0.68% – Morbidly obese controls 6.17% • Lower rates of death for all chronic conditions – Malignancies – Cardiovascular – Endocrine – Infections – Respiratory conditions Christou, et al.

Ann Surgery

Sept 04

Outcomes: Mortality • Obese diabetic patients – 9% mortality at 9 years in surgery group – 28% mortality in control group • Most deaths in controls from CV disease • 89% decrease in relative risk of death in surgery group Pories WJ, et al.

Ann Surgery

Sept 04

Outcomes: Mortality

• Case Matched 7925 patients each – Surgery group vs. severely obese group • Results – Surgery group 40% lower any cause mortality at 7.1 years – 56% decreased mortality for CAD – 92% decrease for diabetes – 60% decrease for cancer

Adams T. N Engl J Med 2007;357:753-61

Outcomes: Weight Loss Preop

Durability of Gastric Bypass

1 yr 10 yr 14 yr

304 lbs 192 lbs 206.5 lbs 204.7 lbs (198-615) (104-466) (130-388)

608 pts < 3% lost to follow-up

(158-270)

Pories, et al.

Ann Surg

1995

Outcomes: Co-Morbid Illnesses

Co-Morbidity

Hypertension Hyperlipidemia Diabetes Asthma DJD DJD Sleep apnea

Resolved

60-65% 70% 90-95% 97% 90-95% 100%

Improved

90% 85% 100% 100% 100% 100%

BLOPE

• Bleeding – Staple line bleed (intra-luminal vs. extra-luminal – Incisional/Abdominal Wall • Leak – GJ – JJ • Obstruction – JJ – Adhesive – Blood Clot • PE

Workup for Early Bariatric Emergencies

• Labs (CBC, BMP, coags) • Obstructive series • CT Abdomen/Pelvis-50-100 ml contrast on the table • CT Chest-ALWAYS get the abdomen too and ALWAYS give 50-100 ml contrast on table • UGI-depends on what primary concern is • Don’t let the skin stand between you and a diagnosis

Late Bariatric Problems

• Internal Hernia • Intussusception • Ventral hernia • Stricture • Ulcer • Gastro-gastric or Gastro-colic fistula

Malabsorption/Nutritional Considerations

• Protein – Primarily absorbed in duodenum – Duodenum is bypassed in RYGB and BPD/DS – Protein levels must be continuously monitored – 60-80 gm/day goal. Adequate protein intake can lead to better outcomes

Malabsorption/Nutritional Considerations

• Fat – Delayed formation of miscelles – Delayed breakdown of dietary fats – Physiologic release of CCK, bile, and lipolytic enzymes is eliminated – Changes are more pronounced after longer limb RYGB and BPD/DS

Malabsorption/Nutritional Considerations

• Carbohydrate Metabolism – Pass through Roux limb as intact polysaccharides – Digestion starts after jejunojejunostomy – Decreased contact time with mucosa leads to decreased absorption

Malabsorption/Nutritional Considerations

• B12 – Decreased pepsin and HCl (decreased cleavage of food bound B12 from protein carrier) – Ingested B12 not exposed to Intrinsic Factor-less absorption – B12 deficiency estimated in 12-33% of RYGB patients – Corrected with supplementation

Malabsorption/Nutritional Considerations

• Folate – Due to decreased intake – Deficiency estimated in 0-38% of RYGB patients – Corrected with supplementation of 1 mg/day

Malabsorption/Nutritional Considerations

• Iron Deficiency – 33-50% of RYGB patients – Decreased HCl leads to less ferric iron – Absorption is normally in duodenum – Must be monitored and supplemented if necessary

Malabsorption/Nutritional Considerations

• Calcium – Deficiency is common – Absorbed in duodenum – Patients can experience bone loss to maintain serum calcium levels

Malabsorption/Nutritional Considerations

• Thiamine – Decreased HCl levels, decreased intake – Deficiency worsened by episodes of vomiting – Thiamine is involved in carbohydrate metabolism – Administration of glucose BEFORE thiamine can precipitate Wernicke’s encephalopathy

Incretins

• GIP (Glucose Dependent Insulinotropic Peptide) – Intestinal K-cells – + insulin secretion, +increases b-cell production – Does not inhibit gastric emptying – Role in CNS is unknown

Incretins

• GLP-1 (Glucagon-Like Peptide 1) – Synthesized by L cells in ileum and colon – Receptors in brain and pancreas – Decreases intestinal motility and gastric emptying – Improves b-cell function – Central and periphery GLP-1 receptors produce reduced food intake – Early production of GLP-1 (like PYY) leads to satiating effect

Effects of RYGB on Ghrelin

• Ghrelin is the only known circulating appetite stimulant – Regulates neuronal activity in weight regulatory centers in brain – Normally increases prior to a meal, decreases afterward – Levels usually inversely correlate with measures of adiposity – Calorie restriction weight loss, chronic exercise, chronic disease, etc., increase ghrelin – Exogenous Ghrelin increases Cortisol, GH, Epi and decreases Adiponectin

Effects of RYGB on Ghrelin

• After RYGB (mean 1.4 yr post-op) – Ghrelin values 77% lower than lean controls – 72% lower than matched obese controls – No prandial variation or diurnal rhythm – This is despite massive weight loss – Most studies support this phenomenon – Exact mechanism is unknown

Mechanisms of DM Resolution

• Decreased levels of Ghrelin – Decreased stress hormones (Cortisol, GH, Epi) – Increased levels of Adiponectin – Administration of Ghrelin suppresses insulin secretion and it antagonizes insulin mediated intra-cellular signaling in relation to glucose metabolism in cultured hepatocytes • If this is a physiologic response then ghrelin is an “anti-incretin” • Suppression of Ghrelin after RYGB would then improve glucose homeostasis

Mechanisms of DM Resolution:Hindgut Hormones

• GLP-1 – Proliferative and anti-apoptotic effects of beta-cells – May indirectly increase insulin sensitivity

Mechanisms of DM Resolution:Foregut Hormones

• Unknown • Ghrelin probably plays a role • Bile acid pathway may play a role (FGF-19-mimics insulin effects on liver) • In rats bypass of the foregut alone improves diabetes (not related to weight loss), so clearly something is going on in the foregut.

• GIP may play a role-decreased GIP protective against obesity and metabolic malfunctions associated with DM II