obesity, metabolic syndrome, and bariatric surgery jon gabrielsen md, facs minimally...

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); 991-1007Bariatric Surgery: Choosing the Optimal Procedure

1999

Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1999, 2008

(*BMI 30, or about 30 lbs. overweight for 5’4” person)

2008

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Definition of obesity

Body Mass Index (BMI) = kg/m2

22- 25 = normal25- 29 = overweight30- 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); 991-1007Bariatric 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


• Adiponectin– Secreted in inverse relation to total body

mass of fat– Low levels implicated in insulin resistance– Weight loss increases adiponectin levels


• 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 Initial operations

• 1970 -1991 “Experimental therapy”

• 1991 NIH Consensus Conference • 1990’s Laparoscopy

• 2000 - 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 Small

Food Passage

Normal

Nutritional Issues

None

Weight Loss 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 Small

Food Passage Normal

Nutritional Issues

None

Weight Loss Modest, Slow

Failure Rate 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

StomachLong and Narrow

Food Passage Normal

Nutritional Issues

None

Weight LossGood/Relatively

Rapid

Failure RateLow to

Moderate

TechniqueModerate 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

Stomach Small

Food PassageBypass lower stomach and small bowel

Nutritional Issues MVI, Fe, Ca, B12

Weight Loss Excellent, Rapid

Failure Rate Low

Technique Complex

Roux en Y Gastric Bypass

Stomach Long and Narrow

Food Passage

Bypass lower stomach and much of small

bowel

Nutritional Issues

MVI, Fe (Anemia), Ca (Metabolic Bone Disease,

B12, Fat Soluble Vitamins

Weight Loss Excellent, Rapid

Failure Rate Low

Technique Complex

BPD-DS

Biliary Pancreatic BypassSleeve 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 0.68%

• includes peri-op mortality 0.4%

– 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

Durability of Gastric Bypass

Preop 1 yr 10 yr 14 yr

304 lbs 192 lbs 206.5 lbs 204.7 lbs

(198-615) (104-466) (130-388) (158-270)

608 pts < 3% lost to follow-up

Pories, et al. Ann Surg 1995

Outcomes: Co-Morbid Illnesses

Co-Morbidity Resolved Improved Hypertension 60-65% 90%

Hyperlipidemia 70% 85%

Diabetes 90-95% 100%

Asthma 97% 100%

DJD 90-95% 100%

Sleep apnea 100% 100% DJD

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


• 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


• Carbohydrate Metabolism– Pass through Roux limb as intact

polysaccharides– Digestion starts after jejunojejunostomy– Decreased contact time with mucosa leads

to decreased absorption


• 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


• Folate– Due to decreased intake– Deficiency estimated in 0-38% of RYGB

patients– Corrected with supplementation of 1

mg/day


• 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


• Calcium– Deficiency is common– Absorbed in duodenum– Patients can experience bone loss to

maintain serum calcium levels


• 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

obesity, metabolic syndrome, and bariatric surgery jon gabrielsen md, facs minimally...

Documents

effect of bariatric

blood leptin

yrs old

obesity rates

life expectancybmi

insulin resistanceweight

blood glucose

absence of leptin