ENDOCRINOLO

GY OF

THE BARIAT

RIC

SURGICAL P

ATIENT

M AT T H E W R. B

R A C K M A N , MD

P I ON E E R V

A L L E Y SU R G I C

A L AS S O C I A

T E S

2 ME D I C

A L CE N T E R D

R I VE , S

P R I NG F I E

L D , MA

Increases all cause mortality - linear relationship with BMI.

BMI > 25 mortality increases for HTN, T2DM, CAD, stroke, gallbladder disease, OA, OSA, cancers (ovarian, endometrial, breast, prostate, colon).

All cause mortality decreased 40% 7 years after RYGB (CAD ↓56%, T2DM↓92%, Cancer ↓60%) Sjostrom (JAMA

2012)

Cost/Benefit ratio

2013 Update to Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical

Support of the Bariatric Surgery Patient. (AACE, Obesity Society, ASMBS)

OBESITY IN THE U.S.AObesity: BMI >/= 30kg/m2 affects 30% of adults based on 2009-2010

data.Morbid obesity : BMI>/= 40 affects 5% of adult population (15 million persons).30

%5%Obesity is an illness unto

itself, a chronic disease, whose only cure is surgical intervention. Yet, only 1% of eligible patients undergo a bariatric surgical procedure.Concept of metabolic surgery OBESITYMORBID OBESITY

NHANES I NHEFS BERRINGTON, NEJM 2010

MORTALITY AND OBESITY

Pooled data from 19 prospective studies showed

that after adjustments for age, physical activity, alcohol consumption, education, and marital

status, both overweight and obesity were associated with increased mortality, which was lowest with a BMI between 20 and 25

• In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality.

• All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

ENDORSED SURGICAL PROCEDURESLaparoscopic Adjustable Gastric Banding (LAGB)Roux-en-Y Gastric Bypass (LRYGB, RYGB)Sleeve Gastrectomy (LSG, SG)Biliopancreatic Diversion with Duodenal Switch (LBPD-DS, BPD-DS)

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Mexico

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Top Ranked Countries for Bariatric Surgery (2008)

EVALUATION OF SUITABILITY AND PREOPERATIVE PREPARATION• Obesity related co-morbidity• Causes of obesity• Comprehensive medical, psychosocial history, examination, lab

testing, and selected imaging procedures.• Informed consent

COMPLICATIONS OF BARIATRIC SURGERY

Dumping: 25-50% of patients (early), <5% (late): nausea, dizziness, palpitations, sweating, vomitting. Poorly understood physiology (GI hormones, autonomic reflexes)

Bone loss femoral neck, hip

mechanisms: 1. adaptation to weight loss and change of physical loading 2. alteration in adipokines from loss of adipose tissue, 3. reduction of Vitamin D, 4. reduction of calcium bioavailability

EARLY SURGICALInfections

DVTLeak

Bleeding

LATE SURGICALStricture

Bowel obstruction

Marginal ulceration

Band erosionBand slippage

MEDICALDumping (early)Dumping (late)

Nutrient deficiencyBone loss

HOLD THE BONE: CALCIUM, VITAMIN-D, AND PTH

OBESITY AND BONEGreater bone mineral density

in the obese (femoral neck, hip, spine)

Close relationship between rapid weight loss and BMD

BMD loss greater in post RYGB pts suggests there is more to the story than simply decreased weight bearing. Johnson J.M., et alEffects of gastric bypass procedures on bone mineral density, calcium, parathyroid hormone, and vitamin D. J. Gastrointest. Surg. 2005; 9

Adipocytes and osteoblasts share common mesenchymal originAdipose tissue extremely active endocrine organ (leptin, adiponectin, TNFα, IL-6) all of which are active in bone remodelling.

Leptin, produced in direct proportion to adipocyte stores, has hormone receptors all over the body (bone marrow stem cells, osteoclasts, osteoblasts). Net bone anabolic effect.

Sustained reductions in leptin have been reported in post RYGB. In lap band reductions occur for six months then rebound to even higher levels beyond that.

7- Dehydrocholesterol

Vitamin D3DietSolar UVB

25(OH)D3

1,25(OH)2D3

Bone

Increased absorption of Ca++ and Phos+

Increased insulin secretion

Improves hematopoiesis

Increases microbicidal Activity Induces differentiation

in immune cells

Increases boneMineralization

Increases osteoclastic differentiation

Increases LVH

Decreases PTHSynthesis and

release

Breast,colon,prostate cells

Vascular cells

Increases smoothMuscle cell proliferationReduces inflammation

Parathyroid gland

Heart

IntestinePancreas

Red Blood Cells

Macrophages

FAT

Decreased Vitamin D late mixing of biliopancreatic secretions

Decreased Ca++ absorption bypassed duodenum and jejunum less acid environment

Rising PTH

Bone resorption

Goldner WSObesity Surgery (2008)

Snijder, Jnl Clin End Met (2005)

Hypovitaminosis in obese (47-84%)Zhou, et al, Jnl Nutr Met (2010)

Postoperative Vit D >/= 3000IU/d

As high as 50,000 IU week or day

Bone density study at two years

Bisphosphonates (IV)

PTH AND BARIATRIC SURGERYPTH increased in post

RYGB pts from 29.4 to 43.1ng/ml one year after surgery.

5% had hyperparathyroidism (>53ng/ml) immediately and 21% after one year.

PTH elevation is secondary to hypocalcemia.

Ghrelin 28 aa hormone produced in fundus of stomach and intestine.

Only known orexigenic peptide known to date.

Increases prior to meals, and decreases rapidly after intake.

Obese have lower fasting levels and decreased postprandial

suppression

Decreases dramatically post RYGB, lesser extent in other

procedures (Cummings, NEJM 2002)

Other results have been conflicting (?orientation of pouch,

sectioning of Vagal nerve)Post banding, may not be long lasting

Peptide YY36 aa peptide secreted by L-cells throughout length of gut (increasing distally)response to calories ingested and inhibits gut motility, gastric and pancreatic secretionInduces satiety (obese may have a deficiency)Increased postprandial PYY in RYGB, SG, VBG, (not Lap Band) within one week post surgery.

GUT HORMONES AND BARIATRIC SURGERY

GLP-1 Released by L- cells postprandially.

Additive effect to PYY

Potent incretin in addition to appetite suppressant

Increased postprandially in RYGB, not lap band, even 20yrs after JIB.

GlicentinOxyntomodulin

insulin secretion, hepatic glucose production, appetite regulation (2003 injected into humans)

GLP-2

CCKMajority synthesized in

duodenum

Released postprandially

Delays gastric emptying, gallbladder contraction, pancreatic secretion, inhibits food intake

“I HAVE LOW THYROID ”

Several studies find high incidence of subclinical hypothyroidism in obese

THYROID AND OBESITY:Pears J, et al, Scott J of Med, 1990

Knudson, et all J.of Clinical Endocrinology, 2005- difference in BMI between highest and lowest TSH was 1.9kg/m2 (5.5kg)

Fox, Archives of Int. Med, 2008- Framingham data for two periods separated by 3.5 years. (TSH .5 to 5.0 then .5 to 10.0) . Body weight increased 5.7kg from lowest to highest quartiles.

Lomenick, Jnl of Pediatrics, 2008- Treatment of acquired hypothyroidism in children did not result in significant changes to weight.

Chikunguwo, et al, Surg. For Obesity and Related Diseases, 2007- association between TSH and weight loss after RYGB

CHILDREN – dysmorphic features, short stature, slow growth velocity, delayed puberty, clinical signs or symptoms of endocrine disorder (hirsuitism, striae, truncal obesity) then LAB TESTING ADULTS – No recommendations, evidence lacking (PCOS)

When should one evaluate for secondary causes of obesity?

Gone in 60 seconds: INSULIN AND THE DIABETIC PATIENT

285 million people with diabetes worldwide.

438 million by 2030.

In 2010 the IDF convened to issue position statement.

Bariatric surgery is an appropriate treatment for people with type II diabetes and obesity not achieving recommended treatment targets with medical therapies, especially when there are other comorbidities.

Surgery should be an accepted option in people who have type II diabetes and a BMI of 35 or more.

Surgery should be considered as an alternative treatment option in patients with a BMI between 30 and 35 when diabetes cannot be adequately controlled by optimal medical regimen, especially in the presence of other major cardiovascular disease factors.

Is diabetes a problem of abnormal lipid metabolism or of glucose metabolism?

Ectopic deposition of FFAInsulin resistanceBeta cell losshyperglycemia

Insulin therapy leads to weight gainACCORD trial: targeting HbA1c to <6% increased 5 year mortality (NEJM 2011)

Shift focus from glycemic control to treating obesity

Gone in 60 seconds: INSULIN AND THE DIABETIC PATIENT

Obesity is a major risk factor for T2DMHigh plasma FFA

inhibit secretion of insulindecrease insulin mediated uptake of peripheral

glucoseAdipocytes

Adiponectin levels decreaseddecreases insulin resistance

Apoptosis and release of pro inflammatory cytokinesGenetic predispositions to diabetes also lead to obesity

Dirksen C, Diabetologia, 2012Improved insulin sensitivityRYGB- hepatic insulin resistance improved immediately (50%

reduction in few days), peripheral later with weight loss improved beta cell glucose sensitivity (GLYP-1)

Parikh, et al, J of Am Col Srg, 2013Metaanalysis: The Role of bariatric surgery in non obese39 studies (22 prospective, 17 retrospective, 3 randomized)BMI <35, 1998-20122010 ADA criteria for remission (HbA1c < 6.5% or fasting

glucose <126 in the absence of glucose lowering medications)

GONE IN 60 SECONDS: INSULIN AND THE DIABETIC PATIENT

Buchwold H, et al, Am Jnl of Med, 2009: overall 78% remission of hyperglycmia in post bariatric patients

Adams, et al, JAMA, 2012: Diabetes remission rates of 62% at 6 years.

Pories, et al, Am Jn of Clin Nutr, 1992: Diabetes improvement early after RYGB

Rubino, Gagner, et al, Ann Surg, 2002: Diabetes remits almost immediately after surgery

Holst JJ, Diabetes, 2011Dixon, et al, JAMA, 2008: Weight loss after lap band. Greater % of weight loss and lower preop glycosylated Hg associated with remission of diabetes, weight loss alone explained the remission.

PERIOPERATIVE MANAGEMENT

Preop target HbA1c <6.5-7.0%, FBG , 110mg/dl (can be liberalized depending on comorbid and treatment factors)

Postop pre prandial, 2 hr postprandial, and bedtime glucose measurements and for hypoglycemic symptoms.

Preop HbA1c for safe surgery?Discontinue all insulin secretagogues postop and carefully monitor insulin

doses.In hospital, non ICU patients: rapid acting pre meal, basal long acting to attain

glycemic targets 140-180 mg/dL)In hospital, ICU: intravenous regular insulin for target 140-180 mg/dLPostprandial hypoglycemia not responsive to dietary manipulation (Consider

NIPHS, factitious, iatrogenic, dumping syndrome, insulinoma)

ENDOCRINOLOGY OF FATObesity leads to low testosterone, SHBG, and low testosterone leads to

obesity. A bidirectional relationship.

Hypogonadism in obese malesLow levels of TT in obese males, reversed after bariatric surgeryIncreased FSH, SHBG, Decreased E2, PRL with obesity surgeryTestosterone causes pluripotential mesenchymal stem cells to

differenciate more towards muscle than fat.

MINGRONE, ET ALL, NEJM, 2012

Redevelop diabetes after RYGB? Arterburn DE a multisite study of long term remission and relapse of type 2 DM followingObesity Surgery 2013Brouwer, 1998 rat fat holds and slowly releases Vit D Br Jnl Nut

THE ENDOCRINOLOGY OF THE BARIATRIC SURGICAL PATIENT:

KEY POINTSObesity is increasing in the U.S. and the world at an alarming rate.Obesity is directly linked to increased mortality.Obesity surgery, the most effective treatment of obesity, has plateaued in recent years.There is a lack of understanding of obesity on the part of the general public and even

physicians which may contribute to lack of aggressiveness in treatment.Current surgical options to treat obesity include LAGB, RYGB, SG, and BPD-DSSurgical complications are at acceptably low rates and pale in comparison to the

potential complications of untreated obesity.Obese patients suffer Vitamin D deficiency pre and post surgery.This deficiency, in concert with impaired Calcium absorption, leads to long term bone

loss.Potential bone loss must be monitored in the bariatric surgical patient and aggressively

treated.

Alteration in gut hormones play an increasingly recognized role in the development of obesity and in the success of surgical treatment.

There is no evidence supporting hypothyroidism as a major contributing factor to obesity.

Preoperative screening for potential causes of obesity should be driven by physical examination findings in children.

There is limited evidence to support preoperative screening of adults for causes of obesity.

A lipocentric focus for treatment of diabetes should aggressively target weight loss and may be more successful than targeting glucose.

THE ENDOCRINOLOGY OF THE BARIATRIC SURGICAL PATIENT: FUTURE IMPLICATIONS

Surgery alone is not likely to be able to keep pace with rising rates of obesity.

More leading medical organizations will treat obesity as a disease rather than a public health problem.

Primary care physicians and specialists will devote a larger portion of their patient care efforts towards treatment of obesity.

Continued elaboration of the role gut hormones play in obesity will lead to other successful treatment options.

The development of pharmacologic treatments of obesity will dramatically change the types of bariatric surgery performed in the U.S. and the world.

Couldn’t you have waited until

CHRISTMAS to get your band deflated !?

DR. BRACKMAN’SOFFICE

HAPPY THANKSGIVING !!