COMPARISON OF NUTRITIONAL DEFICIENCIES AND COMPLICATIONS

FOLLOWING VERTICAL SLEEVE GASTRECTOMY, ROUX-EN-Y GASTRIC BYPASS,

AND BILIOPANCREATIC DIVERSION WITH DUODENAL SWITCH

Kinsy Miller

A Thesis

Submitted to the graduate college of Bowling Green State University in partial fulfillment of the requirements for the degree of

MASTER OF FAMILY CONSUMER SCIENCE

August 2009

Committee:

Martha Sue Houston, Advisor

Rebecca Pobocik

Priscilla Coleman

ii

ABSTRACT

Martha Sue Houston, Advisor

Background: The prevalence of morbid obesity continues to increase and bariatric surgery remains the superior way to treat morbid obesity and related disorders. Although bariatric surgery can produce significant weight loss and alleviate comorbidities, it can also impact nutritional status in ways that have not been adequately studied.

Objective: The objective of the present study was to compare the incidence of nutritional deficiencies, significant complications, and amount of weight loss in patients undergoing three different bariatric surgery procedures: Vertical Sleeve Gastrectomy (VSG); Roux-en-y Gastric

Bypass (RNY-GB); and Biliopancreatic Diversion with Duodenal Switch (BPD-DS). In addition, the role of the registered dietitian (RD) in the outcome of bariatric patients was explored.

Design: A review of all patients undergoing bariatric surgery between April 2006 and December

2007 (n = 119) was conducted from prospectively maintained medical records of a single bariatric surgery practice. Laboratory data related to specific nutrients, hyperlipidemia, and anemia, concerns about compliance with nutrient supplement intake and dietary protein intake, and complication and post-surgery hospitalization rates were compared among patients undergoing the three surgical procedures, VSG, RNY-GB, and BPD-DS. Patients were followed for a minimum of 6 months and a maximum of 18 months after surgery.

Results: Vitamin B12 and calcium deficiency were uncommon after surgery at 1.2% and 2.6%, respectively, among recipients of all surgery types (p = 0.506, and p = 0.092, respectively). The overall rate of folate deficiency was 7.2% and the rate of BPD-DS patients developing folate deficiency after surgery was 37.5% (p = 0.002). The overall rate of anemia was 33.8% and the iii rate of RNY-GB patients developing anemia following surgery was 50% (p = 0.010). Vitamin D deficiency was markedly high at 66.7% of all patients. All of the BPD-DS patients developed deficiency, which was significantly higher than the other groups (p = 0.003). Protein and vitamin

A deficiency were present in 38% and 34.8% of all patients, respectively, but there were no significant differences among surgery types (p = 0.216, and p = 0.141, respectively). Patients who were documented as non-compliant with multivitamin/mineral intake were more likely to develop anemia (p = 0.015) and those who were documented as non-compliant with calcium supplements were more likely to develop vitamin D deficiency (p = 0.022). Weight loss over time among all surgery types was significantly different (p < 0.0001). At 12 months after surgery average percent excess body weight loss (EBWL) was 70.9% for BPD-DS, 59.7% for RNY-GB and 40.2% for VSG. There were no significant differences across groups in the risk of developing complications after surgery relative to weight loss (p = 0.079). Lower albumin levels following surgery were correlated with more complications (r = - 0.31, p = 0.008). RD visits were positively correlated with higher minimum albumin levels (r = 0.24, p=0.025) and greater

%EBWL (r = 0.30, p = 0.002).

Conclusions: Nutritional deficiencies and anemia occurred as a result of all bariatic surgery procedures, both restrictive (VSG) and malabsorptive procedures (RNY-GB and BPD-DS) in the

18 months post-surgery. The incidence of vitamin D deficiency (66.7%) was particularly concerning. Patient intake of recommended levels of nutrient supplements and dietary protein was poor and was related to some of the nutrient deficiencies and anemia. RD visits were beneficial as more RD visits were related to greater weight loss and higher albumin levels following surgery. Increased RD visits and monitoring of nutritional status, nutrient supplement intake and dietary intake of patients pre and post-bariatric surgery is warranted. iv

ACKNOWLEDGMENTS

I would like to acknowledge my advisor, Dr. Sue Houston, for all of the hours and work put in to this project. In addition, I would like to acknowledge my thesis committee members Dr.

Rebecca Pobocik and Dr. Priscilla Coleman for their time and efforts in putting this thesis together. Finally, a thank you to the Bowling Green State University Statistical Lab for all of their hours devoted to analyzing the data presented in this study.

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TABLE OF CONTENTS

Page

CHAPTER I. INTRODUCTION TO OBESITY ...... 1

CHAPTER II. LITERATURE REVIEW...... 4

Introduction to Bariatric Surgeries...... 4

Normal Digestion and Absorption ...... 7

Nutritional Deficiencies...... 8

Comparison of Nutritional Deficiencies Following Bariatric Surgeries ...... 11

STATEMENT OF THE PROBLEM...... 13

RESEARCH QUESTIONS...... 14

CHAPTER III. METHODS...... 15

Nutritional Counseling ...... 16

Indicators of Nutritional Status...... 20

STATISTCAL METHODS...... 23

CHAPTER IV. RESULTS ...... 24

CHAPTER V. DISCUSSION ...... 51

REFERENCES ...... 58

vi

LIST OF FIGURES/TABLES

Figure/Table Page

1 Anatomy of roux-en-y...... 4

2 Anatomy of biliopancreatic diversion with duodenal switch ...... 5

3 Anatomy of vertical sleeve gastrectomy ...... 6

1 Summary of protein, iron, vitamin B12, calcium, and vitamin D deficiency

(% of subjects) following various bariatric surgeries...... 10

2 Number of patients undergoing medically supervised weight loss for 3 or 6

months per type of surgery performed ...... 16

3 Foods included in full and clear liquid diet prior to surgery ...... 17

4 Vitamin, mineral, and protein recommendations per type of bariatric surgery at

0-1 months and 3 + months post-operatively...... 17

5 Protein requirements following bariaric surgery per diet phase ...... 18

6 Optisource™ chewable vitamin and mineral supplement ...... 18

7 Nutrition parameters studied and laboratory data available during the study

perioda ……………… ...... 20

8 Pre-operative characteristics of subjects by surgery typea...... 24

9 Evidence of nutritional deficiencies pre and post-surgery ...... 26

10 Evidence of iron-related nutritional deficiencies pre-and post-surgery ...... 33

11 Evidence of cholesterol related abnormalities pre-and post-surgery a,b ...... 36

12 Documented concerns regarding adequacy of patient intake of multi-vitamin

mineral supplements, calcium supplements, vitamin A & D supplements, and

protein dietary intake after bariatric surgery...... 37 vii

LIST OF FIGURES/TABLES, CONT.

Figure/Table Page

13 Difference in nutritional deficiencies among patients categorized by documented

concerns regarding multivitamin mineral supplement and protein intake following

bariatric surgery ...... 38

14 Differences in nutritional deficiencies related to compliance with calcium

supplementation ...... 41

15 Comparison study of weight loss ...... 43

4 Differences in pounds lost over time among the 3 different surgery types...... 44

5 Differences in Percent Excess Body Weight Loss (%EBWL) over time among the

3 different surgery types...... 45

16 Complications following bariatric surgery a ...... 46 1

CHAPTER I. INTRODUCTION TO OBESITY

Obesity has been linked to almost 300,000 deaths yearly and $117 billion dollars in direct

(preventive, diagnostic, and treatment services) and indirect (value of wages lost by people unable to work because of illness and/or disability and premature death) annual healthcare expenditure in the United States alone (1). The direct cost of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, is estimated to be 39.3 billion dollars per year, which is over 5% of all healthcare costs (2). The prevalence of obesity has been on a steady incline and has more than doubled since 1960; from 13.3 to 32.1 percent of United States adults aged 20 - 74. This incline has been prevalent among both genders, all ages, all racial and ethnic groups, all educational levels, and all smoking levels (3).

Obesity is divided into three classes: Class I obesity corresponds to a BMI between 30 –

34.9 kg/m2, class II obesity corresponds to a BMI between 35 – 49.9 kg/m2, and class III obesity corresponds to a BMI > 40 kg/m2 (25). The prevalence of hypertension, gallbladder disease, type

2 diabetes, sleep apnea, heart disease, and osteoarthritis, increases exponentially from class I to class III obesity (2). Morbid obesity of all classes is also associated with dyslipidemia, complications of pregnancy, menstrual irregularities, hirsutism, stress incontinence, and psychological disorders such as depression (1). Most studies show mortality rate is increased by

10 - 50% in obese individuals compared with individuals in a healthy weight range (BMI = 18.5

- 24.9 kg/m2). This relates to an extra 112,000 deaths per year relative to healthy weight individuals (4).

The primary goals of treatment for morbid obesity are to control co-morbidities, symptoms, complaints, and to minimize psychosocial adverse effects through weight reduction (5).

Unfortunately, conservative medical treatments such as dietary regimens, behavioral 2 modifications, and exercise have largely been unsuccessful in achieving and maintaining long term weight loss results. Even medical therapy remains greatly limited by the unfavorable side effects of the drugs and their inability to result in significant weight loss over the long term (6).

Considering these limitations, bariatric surgery is the only current treatment modality that results in maintained weight-loss and control of medical co-morbidities that are related to morbid obesity (5). Morbid obesity is defined as having a BMI greater than or equal to 40 kg/m2.

Bariatric surgery is a collective term that describes operations that reduce the size of the gastric reservoir with or without a malabsorptive component. Bariatric surgery was first introduced to the United States in the 1950’s (6). There has been extensive evolution of bariatric surgery since that time, but two main principles still exist in combination or on their own. These are restriction and malabsorption. Purely restrictive surgeries include vertical banded gastroplasty (VBG), gastric banding, and vertical sleeve gastrectomy (VSG). Malabsorptive procedures include roux-en-y gastric bypass and biliopancreatic diversion with or without duodenal switch (6). Some of the more common procedures that will be discussed further are the roux-en-y gastric bypass (RNY-GB), biliopancreatic diversion with duodenal switch (BPD-DS).

The VSG will also be discussed further although still considered an investigational procedure.

Although successful in producing weight loss, these surgeries have been shown to result in a number of nutritional deficiencies. RNY-GB and BPD-DS have been shown to cause vitamin

B12, iron, and folate deficiencies. In addition, BPD-DS has also been shown to cause malabsorption of fat-soluble vitamins A, D, E, and K, zinc, and essential fatty acids (8).

Currently, there is very limited research on nutritional deficiencies resulting from VSG.

However, it is thought that restrictive procedures, specifically the vertical banded gastroplasty

(VBG), which is similar in nature to the VSG, may result in nutrient deficiencies related to 3 decreased intake and avoidance of nutrient-dense foods secondary to intolerances (13).

4

CHAPTER II. LITERATURE REVIEW

Introduction to Bariatric Surgeries

Bariatric procedures are divided into one of three categories: restrictive, malabsorptive,

or combination. Restrictive procedures are called such because the surgeon creates a small

gastric pouch with a narrow outlet that restricts the amount of food a patient can eat at one time.

Three common restrictive procedures are performed, VBG, Laparoscopic adjustable gastric

banding (LAGB), and VSG (7). Malabsorptive procedures bypass a portion of the small intestine

so that less food is absorbed. Combination procedures have both malabsorptive and restrictive

components.

The BPD-DS is a malabsorptive procedure in which the mixing of gastric and pancreatic

enzymes with bile is delayed until the final 50 - 100 cm of the ileum. The combination

procedure most commonly used is RNY-GB. This uses both a restrictive and a malabsorptive

component to result in weight loss. Forming a 15 - 30 mL gastric pouch restricts the intake of

food while a small portion (75 - 150 cm) of the small intestine is re-routed. This re-routing

results in less absorption as this segment bypasses the distal stomach, duodenum, and a short

segment of the jejunum (7).

Roux-en-y Gastric Bypass

RNY-GB consists of a small gastric pouch about 20

mL constructed by stapling the proximal stomach in size with a

stomal outlet of about 1 cm in diameter. The length of the

roux-en-y limb varies between 50 - 100 cm in length (6).

Figure 1. depicts changes made to the stomach and intestines Figure 1. Anatomy of roux-en-y 5 during the RNY-GB procedure. Standard RNY-GB is known to cause vitamin B12, iron, and folate deficiencies (8). However, it is also known to be the “gold standard” bariatric procedure in the United States coming into existence in the 1960’s and currently being the most commonly performed procedure. This has allowed for extensive study of the efficacy of the RNY-GB.

RNY-GB results in a long-term weight loss of 49 - 80% of initial excess body weight (IEBW) and an acceptably low mortality rate less than 1.5%; long-term success was measured in 274

RNY-GB patients where 53% of the super obese patients were able to drop to a BMI of 35 kg/m2 or less over 5 years (9). General complications with the RNY-GB include anastomotic ulceration and stenosis, hemorrhage, and anastomotic leak leading to peritonitis, internal hernias, staple line disruption, and acute gastric distention (6).

Biliopancreatic Diversion with Duodenal Switch

BPD-DS has two components. The first component is a

limited vertical gastrectomy and the second is a transection of

the small intestine approximately 250 cm from the ileocecal

valve. The small intestine is then attached at the distal end just

below the duodenum, which is preserved on the vertical gastric

pouch. The proximal end of the intestine is subsequently

attached near the ileocecal valve (6). Figure 2. depicts changes

made to the stomach and intestines during the BPD-DS Figure 2. Anatomy of procedure. This long limb bypass procedure is a more biliopancreatic diversion with duodenal switch aggressive form of bariatric surgery because of restricting intake and inducing weight loss by fat malabsorption. Therefore, in addition to vitamin B12, iron, and folate deficiencies, this type of procedure may also affect absorption of fat-soluble 6 vitamins A, D, E, and K, zinc, and essential fatty acids (8). Although not as common as the

RNY-GB, the BPD-DS procedure has been performed since the mid 1970’s in Italy and made its debut in the United States in 1988. Expected weight loss ranges from 73 - 80% of initial excess body weight (IEBW) and its mortality rate is similar to roux-en-y, 0.5% - 1.9%. A review of long-term results (9 months to over 10 years) was conducted in 987 patients with a mean BMI of

51 kg/m2. Satisfactory weight loss of more than 50% of IEBW was observed in 99.3% of patients

(9). A study of 170 patients receiving the BPD-DS, showed that only 28% of ingested fat is absorbed after surgery, which aided in the 78.1% of excess body weight loss seen in these patients (8). One of the most serious potential nutrition complications is protein malnutrition, resulting in only 57% absorption of ingested protein as a result of intestinal bypass. This protein malabsorption is associated with hypoalbuminemia, anemia, edema, ascites, and alopecia (6).

Vertical Sleeve Gastrectomy

The frequency of performing VSG has increased

significantly over the past 15 years. It is a purely restrictive

procedure involving a gastrectomy of the entire greater

curvature of the stomach leaving in place a 60 - 100 mL

gastric tube along the lesser curvature of the stomach (10).

Figure 3. depicts changes made to the stomach during the

VSG procedure. This surgery was initially invented for use

as the first part of the duodenal switch procedure in patients

with a BMI over 60 kg/m2 because of shorter operating time

Figure 3. Anatomy of vertical and no anastomoses (11). The restriction works to reduce the sleeve gastrectomy size of the stomach and its distention so the patient feels full 7 sooner. Current research has targeted the role of grehlin in weight loss after the VSG. Grehlin is known as the hunger hormone and is predominately secreted in the gastric fundus, which is resected as part of this procedure. Increased satiety from decreased ghrelin production has shown to further trigger increased satiety after surgery (12). Langer, et al found that resection of the fundus after the VSG resulted in lower grehlin levels than after the RNY-GB and VBG. The decrease in grehlin production remained stable up to six months post-operatively. This may explain greater weight loss seen in the VSG than in other purely restrictive procedures (13).

The advantages of this type of procedure are that with the preservation of the pyloric sphincter, dumping syndrome is much less common, it does not result in malabsorption, and it can be used in patients with severe anemia and Crohn’s disease since the intestinal bypass is not done (12). The disadvantages according to Frezza (12) are its irreversibility and risk of stapling complications. A study by Lee et al (11) looked at two-year follow up data after vertical gastrectomy in 216 patients with a mean BMI of 49 + 11 kg/m2. A 60 - 80 mL gastric tube was created and results compared with RYGB, LAGB, and DS. Weight loss was on par with the DS and RYGB procedures after just the VSG alone. Complications occurred in 6.3% of patients versus 7.1% of patients after Lap-band. No conversions to open procedures or deaths occurred

(11).

Normal Digestion and Absorption

The primary role of the stomach is to mechanically process food and to regulate the rate that food passes from the stomach into the small intestine. An intact stomach is not necessary for adequate nutrition, as little absorption takes place there (only water and alcohol are absorbed directly through the gastric lining). Nutrients are absorbed throughout the duodenum, jejunum, and ileum, but the greatest absorption takes place in the middle portion of the small intestine. 8

Carbohydrates are absorbed primarily in the duodenum and jejunum, fats in the jejunum, and

protein in the jejunum and upper ileum. Minerals such as calcium, iron, and magnesium are

predominantly absorbed in the duodenum and fat-soluble vitamins are absorbed mostly in the

lower duodenum and upper jejunum. Finally, water-soluble vitamins are absorbed in the jejunum

and upper ileum (except for B12 which is absorbed in the lower ileum). Therefore, loss of

function in any part of the small intestine impacts absorption and nutrient status (2).

Figure 4. Nutrient deficiencies appear to be more substantial after malabsorptive procedures such

as the RNY-GB and BPD-DS, but they do occur after restrictive procedures such as the VSG and

VBG (14). It is postulated that further deficiency in some nutrients result from decreased intake

and a tendency to avoid nutrient-dense foods post-operatively because of intolerances.

Bloomberg et al’s review (14) presents risk and prevalence of protein deficiency, iron deficiency,

vitamin B12 and folate deficiency, calcium and vitamin D deficiency, thiamine deficiency, and

deficiency of the other fat soluble vitamins A, E, and K with bariatric surgery. These specific

nutrient deficiencies are discussed in detail below.

Nutritional Deficiencies

Protein and Iron Deficiency

Protein deficiency can manifest as hypoalbuminemia, anemia, edema, asthenia, and

alopecia. It is commonly caused from excessive malabsorption after bypassing segments of the

small intestine where protein is primarily absorbed (14). It may also be related to food limitation

and intolerances of high protein foods after surgery. Iron deficiency has been found after both

restrictive and malabsorptive procedures partly due to bypass of the primary site of absorption in

the duodenum and proximal jejunum and related to chronic sources of bleeding such as

menstruation or stomal ulceration (14, 16). 9

Vitamin B12 Deficiency

Vitamin B12 has a complex nature of absorption, which is affected by several facets of restrictive and malabsorptive procedures. First of all, Vitamin B12 must be unbound from food via an acidic gastric environment. Partial gastrectomy greatly reduces the production of stomach acid (21) making it difficult to free B12 from food. Secondly, B12 must bind to intrinsic factor

(IF), produced by the stomach, to be absorbed by the body. Marcuard (15) found that IF was no longer found in gastric juices beyond the bypassed gastric pouch. It is therefore postulated the pathogenesis for vitamin B12 deficiency is the inadequate secretion of IF. Finally, the site of

B12 absorption into the body is through the terminal ileum, which may be bypassed depending on the length of circumvented intestine. This may exacerbate B12 deficiency in RNY-GB or

BPYD-DS patients (22). Vitamin B12 deficiency was found in 36% of patients after gastric bypass at a mean of 22 months postoperatively (14, 15). A dose of 350 ug of B12 was needed to maintain a normal serum level above 150 pmol/L (10). Purely restrictive procedures may not produce the same findings in rate of vitamin B12 and folate deficiency. Patients with the VBG procedure received 350 ug of vitamin B12 for 5 months after surgery and it was found there was no deficiency in B12 or folate, although the mean value for folate fell significantly by 12 months postoperatively (14, 16).

Calcium and Vitamin D Deficiency

Calcium and Vitamin D deficiency are common after surgery secondary to the bypass of the duodenum and upper jejunum, which are the primary sites of absorption for calcium, and the jejunum and ileum, which are the primary sites of absorption for Vitamin D. Even a relative lack of calcium results in increased production of parathyroid hormone (PTH), which signals a release of calcium from bones increasing the risk of osteoporosis (14). Chapin et al (17) found that 10 calcium and vitamin D deficiency occur more often in malabsorptive procedures than in purely restrictive procedures. In a comparison between a group of patients receiving BPD and VBG, the

BPD group had significantly lower serum calcium, 25-hydroxyvitamin D, urine calcium excretion, and higher PTH, alkaline phosphatase, and urinary hydroxyproline/creatinine ratios, which is related to higher bone turnover (14, 17). Table 1 summarizes the frequency of protein, iron, vitamin B12, calcium, and vitamin D deficiency found in the above studies.

Thiamin Deficiency

The risk of thiamine deficiency is a result of reduced intake, frequent vomiting, and malabsorption after bypass of the proximal small intestine. The small intestine is the primary site of absorption for thiamine. However, in a study conducted by Chang et al (2004) 168,010 bariatric patients were followed and the incidence of thiamine deficiency was found to be very low at 0.0002% (14, 18).

Table 1. Summary of protein, iron, vitamin B12, calcium, and vitamin D deficiency (% of subjects) following various bariatric surgeries Study/year Operation/ follow up N % Protein % Iron %Vit B12 %Ca2+/Vit deficiency deficiency deficiency D deficiency Brolin et al/2002 RYGB/2 yr 298 13 45-52 33-37 @ 3 yrs 10/51 Skroubis et al/ RYGB/1 yr 79 1.4 39 33 @ 4 yrs 2002 Distal RYGB/1 yr 3 25 Kalfarentzos et RYGB/20 mo 38 0 13.1 al/1999 Distal RYGB/20 mo 17 5.9 5.9 Brolin et al/1992 RYGB/ 43 mo 45 0 Dolan et al/2004 BPD/ BPD-DS/ 28 mo 134 18 22.9 25/50 Rabkin et BPD-DS/ 3 yrs 589 0 0 al/2004 Skroubis et BPD/ 2 yrs 95 3 44 22 @ 4 yrs al/2002 Nanni et al/1997 BPD 59 3.4 Marceau et BPD/ 79 mo 92 11 al/1995 Kalfarentzos et VBG/ 4 yrs 32 al/2001 Cooper et VBG/ 1 yr 26 0 0 al/1999 Brolin et al/1991 RYGB/ 2 yr 140 37 Slater et al/2004 BPD/ 4 yr 170 48/63 Newbury et BPD/ 32 mo 82 25.9/50 al/2003 11

Study/year Operation/ follow up N % Protein % Iron %Vit B12 %Ca2+/Vit deficiency deficiency deficiency D deficiency Hamoui et BPD-DS/ 9-18 mo 165 25/17 al/2003 Adapted from: Bloomberg, et al 2005 (14)

Fat Soluble Vitamin Deficiency

Fat-soluble vitamin deficiencies are common after bariatric surgery because the site of absorption (the ileum) is bypassed causing the uptake of fat-soluble vitamins to be restricted to the common channel of the BPD (where the alimentary limb is connected to the biliopancreatic limb) (14).

Sixty-one percent of patients became deficient in vitamin A at 28 months after BPD with or without duodenal switch. This high rate of deficiency was found even after an 80% compliance rate with multivitamin supplementation (19). Vitamin E deficiency is uncommon and has not yet been shown to be of clinical significance in patients who are non-compliant with multivitamin supplementation after bariatric surgery (14). There have been few clinical studies researching vitamin K deficiency after bariatric surgery, but the studies that have been done show high rates of deficiency following BPD surgery (50% of BPD patients at 37 months post- op and 50% of BPD-DS patients after 23 months post-op) (19).

Comparison of Nutritional Deficiencies Following Bariatric Surgeries

In a large-scale review, the only significant difference in nutritional deficiencies between groups receiving the RYGB and the BPD were that ferritin deficiency occurred in 37.7% of patients after RYGB and in 15.2% of patients receiving BPD (p = 0.029) (20). One patient receiving RNY-GB and two receiving BPD had albumin levels below 3 g/dl and required total parenteral nutrition for three weeks to correct this deficiency. Furthermore, the two most common deficiencies found were iron and B12. B12 deficiency was estimated to occur at 10.7 months post-operatively in those receiving RYGB and 7.9 months following BPD if no 12 supplementation was given. Iron deficiency appears to be a result of malabsorption of ingested iron due to bypass of the duodenum. Iron, folic acid, and B12 deficiency can result in anemia, the most common nutritional complication in this patient population (21). The incidence of deficiencies increased over time in both groups, except for folate, which showed no deficiency.

Many patients experienced iron deficiency and anemia, especially menstruating women after gastric bypass surgery. All patients should take a multivitamin containing B12 and folate, along with a calcium supplement according to this review (21).

A study by Slater et al (8) compared the rate of fat soluble vitamin deficiency in patients receiving BPD and the results showed the following incidences of deficiency: 69% vitamin A,

68% vitamin K, and 63% vitamin D at four years post-operatively. Vitamin E and zinc deficiency were not shown to increase with time after surgery. Calcium deficiency was shown to increase from 15% to 48% over the four-year study period with an increase in serum parathyroid hormone in 69% of patients at that time. Deficient vitamin A, D, and K values along with calcium and secondary hyperparathyroidism all increased in incidence over time (21).

The documentation of nutritional deficiencies following bariatric procedures has become more prevalent over the past few years. However, many of these deficiencies deserve a closer look, especially following some of the newer restrictive procedures, such as the VSG. This paper will serve to explore the risk of nutritional deficiencies following the combination procedures

RNY-GB and BPD-DS and the restrictive procedure VSG.

13

STATEMENT OF THE PROBLEM

Obesity is linked with hundreds of thousands of deaths and billions of dollars in healthcare expenses every year (1). Obesity is also increasing in prevalence exponentially with an increased risk of co-morbidities as weight increases (2,3). Current methods of treating obesity are aimed at preventing and controlling these co-morbidities, but unfortunately conservative medical treatments have been largely unsuccessful (5,6). Bariatric surgery is currently the only treatment modality that results in maintained weight-loss and control of obesity related co- morbidities (5). However, a well-documented side effect of bariatric surgery is an increased risk of nutritional deficiencies including protein, iron, folate, B12, calcium, and vitamins A and D

(8).

The purpose of this study is to investigate and compare potential nutritional deficiencies and complications after RNY-GB, VSG, and BPD-DS. An additional aim is to examine if the surgery with the greatest amount of weight loss also resulted in the greatest prevalence of nutritional deficiencies. It is expected that the surgeries resulting in the most malabsorption will also result in the highest prevalence of nutritional deficiencies. Finally, we will evaluate the role of the registered dietitian (RD) in the care of bariatric patients and look into whether documented concern over vitamin, mineral, and/or nutrient intake is associated with complications following bariatric surgery.

14

RESEARCH QUESTIONS

1) Are there differences in the evidence of protein, vitamin A, vitamin B12, folate, calcium,

vitamin D, or thiamin deficiencies and anemia among subjects receiving the RNY-GB,

BPD-DS, and VSG procedures?

2) Are documented concerns about nutrient intake during the year post-surgery related to

abnormal laboratory indices of vitamin, mineral, and protein status?

3) Are there differences in weight loss among patients receiving the RNY-GB, BPD-DS, or

VSG procedures?

4) Are there differences in the incidence of serious complications requiring hospitalization

among patients receiving the RNY-GB, BPD-DS, or VSG procedures?

5) Are there relationships among nutritional deficiencies, the amount of weight loss, and

incidence of serious complications?

15

CHAPTER III. METHODS

The Advanced Laparoscopic Bariatric Surgical Associates (ALBSA) was established in

April 2006 at the Center for Weight Loss Surgery in Bowling Green, Ohio. From their established date through December 2007, 180 morbidly obese adult patients have undergone various bariatric procedures at the institution. This surgical group is one of seven in the greater

Toledo, Ohio area, but the only group who offers four different laparoscopic procedures (VSG,

LAGB, RNY-GB, and BPD-DS). The present study analyzing this patient population was approved by the Bowling Green State University Human Subjects Review Board #

H08T032GE5.

A retrospective review of all consecutive patients (n = 119) undergoing bariatric surgery between April 2006 and December 2007 was conducted from prospectively maintained medical records. Charts were excluded for less than 6-month minimum post-operative period and incomplete data; all other patient records were included for the study. From this database of medical records, the nutrient statuses of patients receiving RNY-GB, VSG, or BPD-DS were compared retrospectively. These three bariatric procedures have made up the majority of surgeries performed through ALBSA (RNY-GB 49%, VSG 39%, BPD-DS 12%). All patients were assessed pre-operatively using a multidisciplinary approach (bariatric surgeon, dietitian, psychologist, and internist) in order to select the most favorable type of bariatric procedure and to ensure an optimal physical condition prior to surgery. The selection criteria for the type of bariatric procedure to be performed were the patient’s preoperative BMI, personal dietary habits, pre-existing co-morbidities, and what type of surgery individual insurance policies would approve. If the BMI was > 50 with significant co-morbidities and poor dietary habits, BPD-DS was most often recommended. If the BMI was 40 - 50 with significant co-morbidities, and poor 16 dietary habits, RNYBG was most often recommended. If the BMI was 35-45 with or without co- morbidities, and with good dietary habits, VSG was most often recommended.

Nutrition Counseling

The registered dietitian’s (RD’s) role at the Center for Weight Loss Surgery is multi- factorial. The RD began interaction with many potential bariatric patients 3 - 6 months prior to surgery for the purpose of providing nutritional counseling. A medically supervised weight loss

(MSWL) program prior to surgery is a requirement of most insurance companies. Table 2 shows the breakdown of patients participating in the MSWL program per type of surgery received.

MSWL visits consisted of a one-on-one oral interview and question and answer format with the dietitian. These visits normally lasted 15 - 45 minutes. During this time, patients worked on forming dietary, exercise, and lifestyle behavior changes that are helpful in promoting weight loss and avoiding complications after surgery. The RD and patient developed goals at the conclusion of each monthly visit based on individual needs and focused on making positive lifestyle changes.

Table 2. Number of patients undergoing medically supervised weight loss for 3 or 6 months per type of surgery performed Surgery Type Length of Medically Supervised Weight Loss Program Prior to Surgery RNY-GB VSG BPD-DS n 3 months (4 total visits) 5 6 1

6 months (7 total visits) 5 2 2

All patients met with an RD for an initial bariatric nutrition assessment in which information regarding diet recommendations and requirements before and after surgery was reviewed. This visit normally lasted 45 - 75 minutes. All patients were also seen for a pre- operative visit 2 - 3 weeks prior to surgery. The pre-operative visit normally lasted for 15 - 30 17 minutes. The initial bariatric nutrition assessment and pre-operative visit were also set up as a one-on-one oral interviews and question and answer format with the dietitian. At the time of the pre-operative visit, patients were instructed to start a bariatric full liquid diet two weeks before surgery and to start a bariatric clear liquid diet two days prior to their date of surgery. The purpose of this diet was to reduce the size of the liver and to encourage weight loss prior to surgery in order to minimize risk factors during operation. The foods included as part of the full liquid and clear liquid diets are listed in Table 3.

Table 3. Foods included in full and clear liquid diet prior to surgery Full Liquid Diet Clear Liquid Diet Pureed soups Sugar-free popsicles Sugar free pudding Fruit2O Skim/soy milk Crystal light No sugar added low fat yogurt Water Diet V8 splash Sugar-free beverages Cream of wheat/rice cereal Ice chips Vegetable juice Sugar-free gelatin High protein drink

All patients received similar instructions at assessment for required multivitamin/mineral supplementation and recommended protein intake after surgery, avoidance of alcohol for the first

18 months after surgery, and recommended diet progression after surgery. Table 4 lists vitamin, mineral, and protein recommendations and how they differ per type of bariatric surgery.

Table 4. Vitamin, mineral, and protein recommendations per type of bariatric surgery at 0 - 1 months and 3 + months post-operatively RNY-GB VSG BPD-DS Supplement 0-1 months 3 + months 0-1 months 3 + months 0-1 months 3 + months Optisource 4 tablets 4 tablets 4 tablets 2 tablets 4 tablets 4 tablets Multivitamin Calcium 1000mg 1000mg 1000mg 1000mg 1000mg 1000mg Calcium Calcium Calcium Calcium Calcium Calcium carbonate citrate carbonate citrate carbonate citrate Allergy A&D 1 tablet 1 tablet 0 tablets 0 tablets 3 tablets 3 tablets Protein 30-60 grams 70-80 30-60 grams 70-80 30-60 grams 80-90 grams grams grams

18

During their hospital stay all patients were directed to start their multivitamin/mineral supplementation beginning one week after their surgery date. For their first post-operative week all patients were given the protein goal of 20 - 30 grams per day through the use of protein supplements/drinks. Patients were instructed to advance their diet to full liquids from clear liquids at one week after post-surgery. The amount of protein intake recommended for the remainder of the post-operative period was dependent on the phase of diet and type of bariatric procedure performed. The following table lists the protein requirements after surgery.

Table 5. Protein requirements following bariatric surgery per diet phase Clear Liquid Full Liquid Soft/Pureed Maintenance Surgery Type (grams) VSG 20-30 30-50 50-60 70-80 RYN-GB 20-30 30-50 50-60 70-80 BPD-DS 20-30 30-50 50-60 80-90

The multivitamin recommended by the dietitian was Optisource™ by Resource (Novartis

Medical Nutrition, Fremont). The following chart lists the multivitamin and mineral makeup of

Optisource™. Patients were instructed to take four Optisource™ multivitamins spaced throughout the day except for patients receiving the VSG. These patients were instructed to cut back to two

Optisource™ multivitamins per day starting three months after surgery.

Table 6. Optisource™ chewable vitamin and mineral supplement Amount Per Nutrient Unit Tablet (2.8 g) % Daily Valuea Energy kcal 5 Total Carbohydrate g 1 < 1 Sugars g 1 Vitamin A IU 1875 37 Vitamin C mg 15 25 Vitamin D IU 100 25 Vitamin K mcg 40 50 Thiamin mcg 375 25 Riboflavin mcg 425 25 Niacin mg 5 25 Vitamin B6 mcg 500 25 Folic Acid mcg 200 50 Vitamin B12 mcg 125 2083 Biotin mcg 75 25 Pantothenic Acid mg 2.5 25 19

Amount Per Nutrient Unit Tablet (2.8 g) % Daily Valuea Calcium mg 250 25 Iron mg 7.5 42 Phosphorus mg 50 5 Iodine mcg 37.5 25 Magnesium mg 100 25 Zinc mg 7.5 50 Selenium mcg 17.5 25 Copper mg 0.5 25 Manganese mg 0.5 25 Chromium mcg 30 25 Molybdenum mcg 18.75 25 Sodium mg 5 < 1 a% Daily Value -the percentage of the recommended daily amounts of a nutrient you get from 1 serving. For the purposes of food labels, the government chose an "average" person as someone who needs 2,000 calories a day.

If patients chose not to use this particular type of multivitamin they were encouraged to find a multivitamin comparable in iron, vitamin B12, and thiamin content and one that was chewable for at least the first 3 months after surgery. Additional fat-soluble vitamins were recommended for patients undergoing the bypass procedures (RNY-GB and BPD-DS). The type of fat-soluble vitamin recommended was Allergy A & D ® (Twinlab, American Fork). This fat- soluble multivitamin contains 10,000 IU of vitamin A from retinyl acetate and 400 IU of vitamin cholecalciferol (D3). All patients were recommended to supplement with 1000 mg of calcium after surgery. Calcium carbonate was acceptable for the first 3 months after surgery because it was more available in a chewable form. Long-term a calcium citrate form of calcium supplement was recommended secondary to better absorption. Additional vitamins/minerals (Fe, Ca, B12, etc.) were recommended if lab values drawn after surgery were below normal. Prophylatic ursodeoxycholic acid and pantoprazole were also prescribed routinely after surgery.

Ursodeoxycholic acid was prescribed to help prevent gallstones and pantoprazole was prescribed to limit the production of stomach acid after surgery.

An RD and surgeon and/or physician’s assistant saw all patients at 1 week, 1 month, and

3 months post-operatively. Additionally, the surgeon and/or physician’s assistant saw all patients 20 at 6, 12, and 18 months, and then yearly post-operatively. The RD saw patients at these times only if recommended by the surgeon and/or physician’s assistant. During post-operative visits the registered dietitian reviewed the amount of protein, fluids, and vitamin/mineral supplementation intake as well as recommended levels of each of these nutrients.

Indicators of Nutritional Status

Several nutrition parameters were measured and used to identify nutritional deficiencies before and after bariatric surgery. Each patient was required to get blood work drawn within a year prior to his or her surgery date. Most patients chose to get their blood drawn at Wood

County Hospital, although a few patients did receive their lab work from other area hospitals/healthcare facilities. After surgery, patients typically received orders for blood to be drawn within the first 3 months post-surgery. After this time blood work was usually ordered at

6-month increments until 18 months. After 18 months blood work was ordered on a yearly basis.

Laboratory indices from blood work were stored in patient’s charts located in ALBSA offices for review by healthcare professionals. The following chart (Table 7) lists the nutritional parameters that were compared in this study.

Table 7. Nutritional parameters studied and laboratory data available during the study period. a

Post-Surgery

Pre- 1 3 6 12 18 3-18b Nutrition Parameters Surgery month months months months months months n Vitamin B12 56 27 45 41 28 5 82 25-Hydroxy Vitamin D (D1) 20 20 37 41 26 4 76 1,25 Dihydroxy Vitamin D3 (D2) 18 14 31 36 24 4 66 Vitamin A 20 7 19 24 11 1 46 Albumin 111 57 47 49 33 8 76 Hemoglobin 117 89 49 48 31 9 77 Hematocrit 117 89 49 48 31 9 77 Mean Corpuscular Volume (MCV) 117 89 49 48 31 9 105 21

Post-Surgery

Pre- 1 3 6 12 18 3-18b Nutrition Parameters Surgery month months months months months months Total Cholesterol 103 40 36 42 29 6 69 Potassium 116 89 47 49 33 9 106 Calcium 112 89 48 48 33 9 78 Folate 19 23 33 37 20 3 68 Transferrin 10 23 29 27 18 5 64 Total Iron Binding Capacity (TIBC) 12 28 35 30 21 5 74 Transferrin Saturation 26 33 23 9 7 65 Ferritin 3 8 13 15 15 4 40 High Density Lipoprotein (HDL) 98 10 27 25 22 3 56 Low Density Lipoprotein (LDL) 97 10 28 23 22 4 55 Phosphorous 90 48 43 39 29 5 69 Thiamin 5 6 11 12 1 30 aCounts of subjects with available laboratory data at various times. bCount of subjects with at least one laboratory value available during the 3-18 month post- surgery period.

These nutrition parameters were recorded from each patients chart whenever available and entered into Statistical Analysis System (SAS®, edition 9.1, Cary, North Carolina) to be compared at the following time intervals: pre-operatively, 3, 6, 12, and 18 months post- operatively. Using statistical analysis, the average and minimum values of the above nutrition parameters were used to determine the incidence of nutritional deficiencies among the three different surgery groups; patients who received RNY-GB, patients who received BPD-DS, and patients who received VSG.

Additional information was also collected from patient’s charts. Serious complications requiring additional hospitalization was recorded and compared to determine differences between the three types of bariatric procedures. The reasons for hospitalizations and the care plan during the hospital stay were also noted to determine if there were commonalities.

Demographic data including weight, height, age, and gender were recorded and controlled for.

Percent excess weight loss and total weight loss at the above intervals were also compared 22 among the three different surgery groups. Finally the use of multivitamin compliance after surgery was compared in addition to compliance with protein recommendations after surgery.

The patient and healthcare provider discussed multivitamin and protein intake during the oral interview at the post-operative visits and this information was recorded in the patient’s chart. For the purpose of this study, compliance with multivitamin and protein intake was determined by recording if there was documented concern within the patient’s chart by the surgeon, physician’s assistant, or RD. Documentation of concern was recorded using a quantitative scale: 0 refers to no concern over multivitamin or protein compliance, 1 refers to some concern over multivitamin or protein compliance, and 2 refers to not being compliant with multivitamin or protein requirements.

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STATISTICAL METHODS

The Statistical Analysis System (SAS, Cary North Carolina, edition 9.1) was utilized to analyze the data. Differences among surgeries were tested using analysis of variance (ANOVA) for continuous variables, and Chi Square for nominal data. Repeated measures analysis of variance was used to analyze the effects of time and surgery. Relationships among variables were tested with Pearson’s Correlation Coefficients and linear regression models determined by stepwise regression procedures. Nutritional parameter values are compared within one year pre- operatively and post operatively at approximately 3-month intervals between the groups.

Fisher’s exact test for the investigation of differences in proportion (incidence of deficiency) was used to analyze variables. All reported P-values were two-tailed and significant at a level of p ≤

0.05. 24

CHAPTER IV. RESULTS

A total of 119 procedures were performed over the 15-month study period (59 VSG, 52

RNY-GB, and 8 BPD-DS). Pre-operative characteristics are shown in Table 5. Mean ages were

45.6 years for VSG and BPD-DS and 43.9 years for RNY-GB. Mean age for the entire patient population was 44.9. Mean weight was 302.8 pounds, and mean BMI was 48.6. BPD-DS patients had a higher admission BMI than the other groups (47.7 for VSG, 49 for RNY-GB, and

53.2 for BPD-DS) although initial pre-operative weight was not significantly different among surgery types.

Table 8. Pre-operative characteristics of subjects by surgery typea VSG RNY-GB BPD-DS Characteristic (n=59) (n=52) (n=8) Age (y) Mean + SD 45.6 + 12.0 43.9 + 11.9 45.6 + 9 Range 19-65 21-63 34-61 Admission BMI Mean + SD 47.6 + 10.2 49.1 + 7.8 53.2 + 11.2 Range 35.7-89.9 34.7-71.8 44.3-78 Gender, (%) Male 18.7 15.4 50 Female 81.3 84.6 50 aVSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

The majority of patients receiving the VSG or RNY-GB were female (81.3% and 84.6%, respectively) where only half of the patients receiving the BPD-DS were female. However, gender was not significantly different between surgeries (p = 0.069). This could be related to the small number of patient’s receiving the BPD-DS procedure. All operations were primary except for two that were revisions from VBG. One VBG was revised to VSG and the other was revised to RNY-GB. There was one conversion from laparoscopic to open procedure, which occurred in the BPD-DS group. The first stage procedure, which is equivalent to a VSG, was done when there were excess adhesions or when the patient was too high a risk to be under anesthesia for the 25 length of the entire PBD-DS procedure. One patient who was scheduled for RNY-GB and four patients scheduled for BPD-DS only had the first stage procedure. One patient who received

VSG and one who received RNY-GB were recommended for revisions by the surgeon secondary to inadequate weight loss/weight regain after surgery.

All patients included in the study were a minimum of six months post surgery. An average of 66% of patients completed their six-month post-op visit (64% VSG, 65% RNY-GB, and 87.5% BPD-DS) and 84.2% of eligible patients completed their 12-month follow up visit

(80.8% VSG, 88% RNY-GB, and 83% BPD-DS). Finally, 37% of eligible patients completed their 18-month follow up visit (40% VSG, 23% RNY-GB, and 75% BPD-DS). The findings for laboratory values pre-operatively, up to 1 month post-operatively and 3 - 18 months post- operatively are compiled in Table 6. The post-operative time frame is split into 0 - 1 months post-surgery and 3 - 18 months post- surgery to control for the influence of the actual operation on laboratory values in the immediate post-operative period because many of these laboratory values could be influenced by the surgery itself.

Research Question 1: Are there differences in the evidence of protein, vitamin A, vitamin B12, folate, calcium, vitamin D, or thiamin deficiencies and anemia among subjects receiving the

RNY-GB, BPD-DS, and VSG procedures?

The following table (Table 9) lists the normal reference range, the average range post surgery and the percent of abnormal reference ranges within three time periods for several different nutrition parameters. The three time periods were pre-surgery, 0 - 1 months post- surgery, and 3 - 18 months post surgery. The percent of abnormal reference ranges were used to identify nutrition deficiencies. 26

Table 9. Evidence of nutritional deficiencies pre and post surgery

Incidence of Abnormal Value, % (n) Normal Average Reference Post-surgery Post-surgery Post-surgery Range 3-18 mo** Pre-surgery 0-1 month 3-18 months Calcium, mg/dl 8.1-10.2 Below Normal All Surgeries 9.2 + 0.4 0 (0/112) 5.6 (5/89) 2.6 (2/78) VSG 9.3 + 0.3 a 0 (0/53) 7.0 (3/43) 0 (0/35) RYN-GB 9.2 + 0.4 a 0 (0/51) 2.5 (1/40) 2.8 (1/36) BPD-DS 8.8 + 0.2 b 0 (0/8) 16.7 (1/6) 14.3 (1/7) p 0.0003 N/A 0.322 0.092

Phosphorus, mg/dl 2.3-4.7 Below Normal All Surgeries 3.6 + 0.5 2.2 (2/90) 14.6 (7/48) 4.4 (3/69) VSG 3.5 + 0.5 2.3 (1/44) 15.8 (3/9) 0 (0/29) RYN-GB 3.7 + 0.4 2.5 (1/40) 16.0 (4/25) 3.1 (1/32) BPD-DS 3.6 + 0.9 0 (0/6) 0 (0/4) 25.0 (2/8) p 0.539 0.927 0.689 0.008

Potassium, mEq/l 3.5-4.0 Below Normal All Surgeries 3.9 + 0.4 8.6 (10/116) 21.4 (19/89) 16.7 (13/78) VSG 4.0 + 0.4 10.5 (6/57) 23.3 (10/43) 17.1 (6/35) RYN-GB 3.9 + 0.3 7.8 (4/51) 12.5 (5/40) 11.4 (4/35) BPD-DS 3.7 + 0.4 0 (0/8) 66.7 (4/6) 37.5 (3/8) p 0.129 0.589 0.009 0.202

Vitamin B12, pg/ml 180-914 Below Normal All Surgeries 559 + 252 3.6 (2/56) N/A 1.2 (1/70) VSG 515 + 190 0 (0/28) N/A 3.3 (1/30) RYN-GB 575 + 295 8.7 (2/23) N/A 0 (0/33) BPD-DS 677 + 255 0 (0/5) N/A 0 (0/7) p 0.277 0.226 0.509

Folate, ng/ml > 5.2 Below Normal All Surgeries 17.0 + 7.5 5.3 (1/19) N/A 7.4 (5/68) VSG 17.1 + 8.1 9.1 (1/11) N/A 4.0 (1/25) RYN-GB 17.6 + 6.9 0 (0/6) N/A 2.9 (1/35) BPD-DS 14.1 + 8.6 0 (0/2) N/A 37.5 (3/8) p 0.491 0.681 N/A 0.002

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Incidence of Abnormal Value, % (n) Normal Average Reference Post-surgery Post-surgery Post-surgery Range 3-18 mo** Pre-surgery 0-1 month 3-18 months 1.25 Dihydroxy <30 Mild Deficiency Vitamin D pg/ml <20 Moderate Deficiency 33.3 (6/18) 43.1 (29/66) All Surgeries 29.7 + 12.0 50 (9/18) N/A 23.1 (15/66) 37.0 (11/28) VSG 29.4 + 9.3 a N/A N/A 25.9 (7/28) 53.1 (17/32) RYN-GB 32.6 + 13.2 a N/A N/A 9.4 (3/32) 16.7 (1/6) BPD-DS 15.2 + 4.3 b N/A N/A 83.3 (5/6) p 0.004 0.003

3.5-3.0 Mild Deficiency 3.0-2.5 Moderate Deficiency Albumin, mg/dl < 2.5 Severe Deficiency 28.3 (26/92) 7.6 (7/92) All Surgeries 3.7 + 0.3 15.3 (17/111) 40.4 (23/57) 2.2 (2/92) 20.4 (9/44) 4.6 (2/44) VSG 3.8 + 0.3 15.1 (8/53) 40.7 (11/27) 2.3 (1/44) 30 (12/40) 10 (4/40) RYN-GB 3.7 + .32 17.7 (9/51) 40.0 (10/25) 2.5 (1/40) 62.5 (5/8) 12.5 (1/8) BPD-DS 3.5 + 0.2 0 (0/7) 40.0 (2/5) 0 (0/8) p 0.067 0.477 0.998 0.216

Total Cholesterol, mg/dl < 140 Below Normal All Surgeries 171 + 38 6.8 (7/103) 35 (14/40) 27.5 (19/69) VSG 184 + 37 8.2 (4/49) 46.7 (7/15) 16.7 (5/30) RYN-GB 166 + 36 6.3 (3/47) 30 (6/20) 22.6 (7/31) BPD-DS 141 + 32 0 (0/7) 20 (1/5) 85.5 (7/8) p 0.0009 0.716 0.447 0.0003

Thiamin, ug/dl 1.2-4.0 Below Normal All Surgeries 2.97 + 2.22 N/A N/A 6.7 (2/30) VSG 3.07 + 2.34 N/A N/A 0 (0/14) RYN-GB 3.0 + 2.32 N/A N/A 14.3 (2/14) BPD-DS 2.1 + 0.14 N/A N/A 0 (0/2) p 0.854

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Incidence of Abnormal Value, % (n) Normal Average Reference Post-surgery Post-surgery Post-surgery Range 3-18 mo** Pre-surgery 0-1 month 3-18 months Vitamin A, ug/dl 38-98 Below Normal All Surgeries 62.4 + 86.0 10.0 (2/20) N/A 34.8 (16/46) VSG 73.7 + 106 8.3 (1/12) N/A 20.0 (4/20) RYN-GB 60.7 + 78.6 12.5 (1/8) N/A 42.1 (8/19) BPD-DS 34.8 + 9.5 0 (0/0) N/A 57.1 (4/7) p 0.594 0.761 0.141 a Statistically different among surgery types, ANOVA for mean laboratory values, or Chi Square for the incidence of abnormal concentrations. b Mean ± SD. N/A = data not available VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

Vitamin A

The cumulative incidence (# of cases of vitamin A deficiency that developed over the 15

month study period) of vitamin A deficiency was 35.6% post-surgery. Although there was

not a statistical difference among the types of surgery in the incidence of vitamin A

deficiency (p = 0.172) at 3 - 18 months post-op incidence was high among all surgery

groups. Twenty-one percent of VSG patients became vitamin A deficient, 52% of RNY-GB

became vitamin A deficiency, and 57% of BPD-DS patients became vitamin A deficient. The

average vitamin A level among surgeries were: 75.3 ± 108.7 ug/dl, 60.7 ± 78.6 ug/dl, and

34.8 ± 9.5 ug/dl for VSG, RNY-GB, and BPD-DS, respectively. The number of subjects in

the present study, and large variation in serum vitamin A concentrations limited the ability to

demonstrate a statistically significant difference in minimum, or average serum vitamin A

levels. Another surprising finding was that 10% of patients screened for vitamin A status

prior to surgery were found to be deficient, with levels below 38 ug/dl.

29

Vitamin B12

Vitamin B12 deficiency was uncommon among all surgery types. In fact there was a greater percentage of patients deficient in vitamin B12 prior to surgery than post-operatively.

Only one subject became deficient in vitamin B12 after surgery, while two people were found to be deficient in vitamin B12 prior to surgery. This could be due to supplementation after surgery as the recommended dose of the Optisource™ multivitamin contains 500 mcg of vitamin B12 (8332 % Daily Value). The patient who became deficient in B12 after surgery received the VSG procedure, while the two patients who were deficient in vitamin B12 prior to surgery were patients who received the RNY-GB. Average vitamin B12 levels after surgeries are as follows: 572.1 + 190 pg/ml for VSG, 637.7 + 295 pg/ml for RNY-GB, and

751.1 + 255 pg/ml for BPD-DS. Although there appears to be large differences in the average vitamin B12 level among surgery types this difference is not significant (p = 0.192).

This may be partly due to the large standard deviation of serum vitamin B12 levels within each surgery group.

Folate

Folate deficiency developed in 7.35% of this patient population following bariatric surgery. The risk of developing folate deficiency significantly differed among the three surgery groups (p = 0.002). Of patients receiving the BPD-DS, 37.5% became deficient in folate compared to only 2.9% of patients receiving the RNY-GB and 4% of patients receiving the VSG. This demonstrates that there are much greater problems with folate deficiency for BPD-DS patients than with the other two surgery groups. However, the small amount of BPD-DS patients must be taken into consideration as it limits the statistical significance of this finding. It should also be noted that the difference in the development of 30 folate deficiency is not statistically significant between the VSG and the RNY-GB procedures (p = 0.808).

Calcium

In addition to folate, the percentage of patients who became calcium deficient after the

BPD-DS procedure was noticeably larger than the percentage of patients who became calcium deficient with the other procedures (14% in BPD-DS compared to 0% of patients who received VSG and 2.8% of patients who received RNY-GB). Although this difference appears to be large, it is not significant. This may be related to the insufficient number of subjects within the BPD-DS group (p = 0.092). The risk of developing calcium deficiency within the study period appeared to be low overall, except for patients receiving the BPD-DS.

Vitamin D

There were significant deficiencies in vitamin D 1, 25-Dihydroxy (D3) levels following bariatric surgery. Vitamin D3 deficiency was separated into two groups: mild (20 - 30 pg/ml) and moderate (< 20 pg/ml). A total of 43.1% of patients developed a mild vitamin D3 deficiency and 23.1% developed a moderate vitamin D3 deficiency. There was a significant difference in both the average and minimum serum vitamin D3 levels among surgery groups

(p = 0.004, p = 0.005, respectively). This difference in both average and minimum serum vitamin D2 levels occurred between the VSG and BPD-DS groups and between the RNY-GB and BPD-DS groups. There was no significant difference between the VSG and RNY-GB groups (p = 0.245). However, the average vitamin D3 level 3 - 18 months post-surgery among all surgery types was below the normal reference range (29.7 pg/ml). In spite of the small number of patients within the BPD-DS group it is still significant to note that all of the patients within this group developed either a mild or severe vitamin D2 deficiency 3 - 18 31 months after surgery (16.7% mild and 83.3% moderate). This was significantly different from the percentage of vitamin D deficiency seen in either the VSG (37% mild and 25.9% moderate) or the RNY-GB (53.1% mild and 9.4% moderate) groups (p = 0.003).

Unfortunately, vitamin D3 levels were not typically measured prior to surgery, but according to other studies vitamin D3 deficiency is also commonly seen prior to bariatric surgery.

Albumin

Albumin deficiency was also separated into groups depending upon severity (3.0 - 3.5 mg/dl = mild deficiency, 3.0 - 2.5 mg/dl = moderate deficiency, and < 2.5 mg/dl = severe deficiency (33). At 0 - 1 month post-surgery the rate of albumin deficiency was fairly consistent across all surgery types (40.7% for VSG, 40.0% for RNY-GB, and 40.0% for

BPD-DS). However, the rate of total albumin deficiency (< 3.5 mg/dl) seen 3-18 months after surgery was statistically different among surgery types: 20.4% of VSG patients, 30% of

RNY-GB patients, and 62.5% of BPD-DS patients developed albumin deficiency after surgery (p = 0.024). The average serum albumin level among surgeries 3-18 months post-op were: 3.8 ± 0.34 mg/dl, 3.7 ± 0.32 mg/dl, and 3.5 ± 0.22 mg/dl for VSG, RNY-GB, and

BPD-DS, respectively. Neither the average nor the minimum serum albumin levels proved to be significantly different among surgery groups (p = 0.067 and p = 0.233, respectively). Even the differences in the rate of albumin deficiency among surgery groups became insignificant when breaking down albumin deficiency by severity (p = 0.216). Out of the total patient population, 28.3% developed mild albumin deficiency, 7.6% developed moderate albumin deficiency, and 2.2% developed severe albumin deficiency in the post-operative period (1-18 months).

32

Cholesterol

Cholesterol deficiency was defined as having a cholesterol level below 140 mg/dl. There were significant differences in the average cholesterol level 3 - 18 months after surgery among the three surgery groups (p = 0.009). In addition, the prevalence of cholesterol deficiency from 3 - 18 months post-surgery was significantly different (p = 0.0003). The average cholesterol level from 3 - 18 months post-surgery for VSG, RNY-GB, and BPD-DS was 184 + 37 mg/dl, 167 + 36 mg/dl, and 141 + 32 mg/dl, respectively. The percent of cholesterol deficiency from 3 - 18 months after surgery was 16.7% for VSG, 22.6% for

RNY-GB, and 85.5% for BPD-DS. Thus, nearly all BPD-DS patients were deficient in cholesterol sometime during the 3 - 18 month time period following surgery. Cholesterol deficiency is often an indicator used to measure protein-energy malnutrition, therefore it is expected that BPD-DS patients would have lower cholesterol levels because of the greater amount of malabsorption with the BPD-DS procedure.

Electrolytes

BPD-DS patients had a significantly greater rate of developing electrolyte deficiencies compared to patients receiving the RNY-GB or the VSG. Twenty-five percent of BPD-DS patients developed a phosphorus deficiency 3 - 18 months after surgery compared to only

3.1% for patients receiving RNY-GB and 0% of patients receiving the VSG (p = 0.008). A significantly higher number of BPD-DS patients developed a potassium deficiency in the immediate post-surgery period (0 - 1 months post-op): 67% for BPD-DS, 23% for VSG, and

13% for RNY-GB (p = 0.009). Surprisingly, even at 3 - 18 months after surgery (the time period that is no longer impacted by surgery itself) there were still a great deal of BPD-DS patients (37.5%) who were deficient in potassium. All of the surgeries showed that 33

potassium deficiency within 0 - 1 month after surgery was an issue (an average of 21.4% of

people became potassium deficient), but only in the BPD-DS population did potassium

deficiency continue past the immediate post-operative phase.

Table 10. Evidence of iron-related nutritional deficiencies pre-and post-surgery Incidence of Abnormal Value, % (n) Normal Average Reference Post-surgery Post-surgery, Post-surgery, Range 3-18 mo b Pre-surgery 0-1 month 3-18 months Anemiac Below Normal All Surgeries 39.3 + 3.4 9.4 (11/117) 48.3 (43/89) 33.8 (26/77) VSG 39.9 + 3.8 8.8 (5/57) 47.7 (21/44) 15.6 (5/32) RYN-GB 38.5 + 2.8 11.5 (6/52) 48.7 (19/39) 50.0 (19/38) BPD-DS 41 + 3.0 0 (0/8) 50.0 (3/6) 28.6 (2/7) p 0.083 0.567 0.992 0.009 MCVd, fL 83-99 Below Normal All Surgeries 87.2 + 4.4 12.0 (14/117) 12.4 (11/89) 16.2 (17/105) VSG 88.2 + 4.1 10.5 (6/57) 6.8 (3/44) 9.8 (5/51) RYN-GB 86.4 + 4.8 13.5 (7/52) 20.5 (8/39) 23.4 (11/47) BPD-DS 87.7 +3.4 12.5 (1/8) 0 (0/6) 14.3 (1/7) p 0.238 0.894 0.106 0.187 20-120 female Ferritin, ng/ml 20-300 male Below Normal All Surgeries 56.3 + 56.1 N/A N/A 12.5 (5/40) VSG 49.9 + 43.9 N/A N/A 5.3 (1/19) RYN-GB 72.9 + 68.7 N/A N/A 17.7 (3/17) BPD-DS 15.8 + 7.0 N/A N/A 25 (1/4) p 0.148 0.388 180-200 Mild Deficiency 160-180 Moderate Deficiency Transferrin, ug/dl <160 Severe Deficiency 9.4 (6/64) 6.3 (4/64) All Surgeries 247.4 + 47.2 N/A N/A 3.1 (2/64) 0 (0/29) 6.9 (2/29) VSG 254.2 + 51.3 N/A N/A 0 (0/29) 10.3 (3/29) 3.5 (1/29) RYN-GB 249.6 + 40.6 N/A N/A 3.5 (1/29) 50 (3/6) 16.7 (1/6) BPD-DS 203.9 + 38.4 N/A N/A 16.7 (1/6) p 0.054 0.0001 34

Incidence of Abnormal Value, % (n) Normal Average Reference Post-surgery Post-surgery, Post-surgery, Range 3-18 mo b Pre-surgery 0-1 month 3-18 months Transferrin Saturation, (%) 20-55 Below Normal All Surgeries 29.7 + 28.1 N/A N/A 29.2 (19/65) VSG 37.8 + 34.1 N/A N/A 17.2 (5/29) RYN-GB 22.8 + 21.2 N/A N/A 39.4 (13/33) BPD-DS 28.7 + 11.7 N/A N/A 33.3 (1/3) p 0.108 0.158 TIBC, ug/dld < 425 Above Normal All Surgeries 344 + 69 8.3 (1/12) 7.1 (2/28) 13.6 + (8/59) VSG 357 + 71 N/A 16.7 (2/12) 16.7 (4/24) RYN-GB 341 + 56 N/A 0 (0/12) 10.3 (3/29) BPD-DS 312 + 106 N/A 0 (0/4) 16.7 (1/16) p 0.346 0.238 0.778 a Statistically different among surgery types, ANOVA for mean laboratory values, or Chi Square for the incidence of abnormal concentrations. b Mean ± SD. N/A = data not available cHgb, Hemoglobin cut-offs, <12 g/dL for females and < 13.5 g/dL for men; Hct, hematocrit cut-offs <37% for females and < 40% for males. dMCV, mean corpuscular volume;TIBC, total iron binding capacity VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

Transferrin

The rate of transferrin deficiency was separated into mild, moderate, or severe depending

on serum transferrin levels (180-200 ug/dl, 160-180 ug/dl, and < 160 ug/dl, respectively).

The incidence of mild, moderate, and severe transferrin deficiency was 9.4%, 6.3%, and

3.1% post-surgery, respectively. In comparing transferrin levels among the three different

surgery types, there was a significant difference in the minimum level of transferrin among

the surgery groups (p = 0.008). This difference occurred between the BPD-DS and the VSG

and between the BPD-DS and the RNY-GB surgery groups. The minimum transferrin level

among surgeries was: 247.3 + 47.4 ug/dl, 243.2 + 43.7 ug/dl, and 184.2 + 203.9 ug/dl for

VSG, RNY-GB, and BPD-DS, respectively. There was also a significant difference in the 35 rate of severe transferrin deficiency experienced among surgery groups (p = 0.0009).

Transferrin deficiency following bariatric surgery may indicate a protein deficiency. The

VSG had no severe transferrin deficiencies, the RNY-GB had 3.5%, and the BPD-DS had

16.7%. There was no significant difference in the minimum or average transferrin levels or in the rate of transferrin deficiency between the VSG and RNY-GB.

Anemia

Anemia was determined by having either deficient hemoglobin (< 12 g/dl for women, <

15 g/dl for men) or deficient hematocrit (< 37% for women, < 40% for men) levels. The rate of hemoglobin and hematocrit deficiency post-surgery was high among all surgery types.

The rate of deficiency for hemoglobin was 30.5%, 48.1%, and 62.5% for VSG, RNY-GB, and BPD-DS, respectively. Although the differences in deficiency rates were notable among surgery types they were not significantly different (p = 0.071). For hematocrit, the rates of deficiency were 44.1%, 57.7%, and 62.5% for VSG, RNY-GB, and BPD-DS, also a notable, but not significant difference (p = 0.288). The high rate of deficiency 0 - 1 months post surgery (average deficiency of 48.3%) was as expected secondary to possible blood loss during surgery and over-dilution while in the hospital following surgery. However, it was still surprising that an average of 34% of patients were anemic at some point during the 3-18 month time frame following surgery. Similarly, patients receiving BPD-DS had a higher rate of iron deficiency compared to patients receiving RNY-GB or VSG: 37.5%, 13.5%, and

8.5%, respectively. According to multiple iron status indices (ferritin, transferrin, transferrin saturation, and TIBC) approximately 15 - 30% of patients likely experienced iron deficiencies within the 3 - 18 month period following surgery. 36

Table 11. Evidence of cholesterol related abnormalities pre-and post-surgery a,b

Incidence of Abnormal Value Normal Mean Post- Reference surgery 3-18 Post-surgery, Post-surgery, Range months Pre-surgery 1 month 3-18 months Mean + SD % (n) High Total Cholesterol, mg/dl > 200 Above Normal All Surgeries 172 + 38 38.8 (40/103) 12.5 (5/40) 22.7 (15/69) VSG 184 + 37 36.7 (18/49) 13.3 (2/15) 33.3 (10/30) RYN-GB 167 + 36 44.9 (21/47) 15.0 (3/20) 12.9 (4/31) BPD-DS 141 + 32 14.3 (1/7) 0 (0/5) 12.5 (1/8) p 0.009 0.280 0.658 0.123

>50 female HDL mg/dl >40 male Below Normal All Surgeries 46.3 + 17.0 63.2 (62/98) N/A 53.6 (30/56) VSG N/A 53.2 (25/47) N/A 44.0 (11/25) RYN-GB N/A 69.6 (32/46) N/A 54.7 (13/24) BPD-DS N/A 100 (5/5) N/A 85.7 (6/7) p 0.057 0.147 a Mean ± SD or percent (n); N/A = data not available b Statistically different among surgery types, ANOVA for mean laboratory values, or Chi Square for the incidence of abnormal concentrations. VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

High total cholesterol and HDL levels were also evaluated following surgery. There was no significant difference in the rate of high total cholesterol levels (> 200 mg/dl) 3 - 18 months following surgery, but the average high cholesterol levels were significantly different among surgery types (p = 0.009). VSG patients had the highest average high total cholesterol level (184 mg/dl) and BPD-DS patients had the lowest average high total cholesterol level (141 mg/dl).

There was a large difference in abnormal HDL levels prior to surgery, although this difference did not quite reach significance (p = 0.057). HDL levels under 50 mg/dl were abnormal for women, where 40 mg/dl and under were abnormal for men. Abnormal HDL levels prior to 37 surgery were 53.2% abnormal for VSG, 69.6% abnormal for RNY-GB, and 100% abnormal for

BPD-DS. There was a negative correlation between average cholesterol levels and 1) maximum number of pounds lost (r = - 0.20) and 2) maximum % EBWL (r = - 0.34) after surgery. In addition there was a strong negative correlation between % EBWL and average LDL cholesterol levels (r = - 0.29). The strongest association was between Maximum % EBWL and lowest cholesterol level (r = - 0.43) 3 - 18 months post-surgery. This equates to greater % EBWL being associated with lower total cholesterol levels.

Research Question 2: Are Documented Concerns about Nutrient Intake during the Year Post- surgery Related to Abnormal Laboratory Indices of Vitamin, Mineral, and Protein Status?

Table 12 shows there were no significant differences in the level of compliance with multivitamins, calcium, vitamin A & D supplementation, or protein intake following surgery according to surgery type. Patients who received the VSG were not required to take vitamin A &

D supplementation after surgery, which is why that group is not included for the vitamin A & D column. There were a considerable amount of patients not meeting recommendations for multivitamin, protein, calcium, and vitamin A & D intake across all surgery types following surgery (12.5 - 62.5%).

Table 12. Documented concerns regarding adequacy of patient intake of multi-vitamin mineral supplements, calcium supplements, vitamin A & D supplements, and protein dietary intake after bariatric surgery Multi-vitamin Vitamin A Mineral Protein Calcium & D Pts meeting needs, % (n) VSG 40.4 (23/57) 25.9 (15/58) 41.1 (23/56) N/A RNY-GB 46.0 (23/50) 31.3 (15/48) 42.0 (21/50) 51.0 (25/49) BPD-DS 37.5 (3/8) 25.0 (2/8) 37.5 (3/8) 37.5 (3/8) Pts somewhat meeting needs, % (n) VSG 35.1 (20/57) 34.5 (20/58) 12.5 (7/56) N/A RNY-GB 20.0 (10/50) 34.5 (17/48) 10.0 (5/50) 8.2 (4/49) BPD-DS 50.0 (4/8) 50.0 (4/8) 25.0 (2/8) 0 (0/8) 38

Multi-vitamin Vitamin A Mineral Protein Calcium & D Pts not meeting needs, % (n) VSG 24.6 (14/57) 39.7 (23/58) 46.4 (26/56) N/A RNY-GB 34.0 (17/50) 33.3 (16/48) 48.0 (24/50) 40.8 (20/49) BPD-DS 12.5 (1/8) 25.0 (2/8) 37.5 (3/8) 62.5 (5/8) p a 0.2776 0.8515 0.8326 a Chi Square analysis. VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

Table 13 reviews how the average value of several nutrient indices post-surgery may by impacted by levels of compliance with multivitamin and protein intake. In addition, it summarizes whether becoming deficient in these nutrients is dependent on the level of compliance with multivitamin and protein intake following surgery (3 - 18 months post-surgery).

Table 13. Differences in nutritional deficiencies among patients categorized by documented concerns regarding multivitamin mineral supplement and protein intake following bariatric surgery Average Value Incidence of Abnormal Value Nutrient 3-18 mo post-surgery 3-18 mo post-surgery 1.25 dihydroxy Vitamin D3, pg/ml Mean + SD % (n) Multi-Vitamin Mineral Supplement Intake Meeting needs 32.4 + 15.4 54.2 (13/24) Somewhat meeting needs 23.8 + 9.9 64.7 (11/17) Not meeting needs 24.9 + 7.8 73.7 (14/19) p 0.041 0.546 Protein Intake Meeting needs 29.1 57.1 (8/14) Somewhat meeting needs 26.3 69.6 (16/23) Not meeting needs 31.1 60.9 (14/23) p 0.402 0.801

Albumin, g/dl Multi-Vitamin Mineral Supplement Intake

Meeting needs 3.7 + 0.3 3.1 (1/32)

Somewhat meeting needs 3.7 + 0.3 15.4 (4/26)

Not meeting needs 3.5 + 0.6 20 (5/25) p 0.143 0.137 39

Average Value Incidence of Abnormal Value Nutrient 3-18 mo post-surgery 3-18 mo post-surgery Protein Intake Meeting needs 3.7 + 0.3 31.3 (5/16) Somewhat meeting needs 3.6 + 0.4 28 ( 7/25) Not meeting needs 3.5 + 0.4 34.6 (9/26) p 0.393 0.604

Folate, ng/ml Multi-Vitamin Mineral Supplement Intake

Meeting needs 15.4 + 5.8 0 (0/24)

Somewhat meeting needs 14.2 + 8.1 0 (0/16)

Not meeting needs 15.0 + 7.6 10 (2/20) p 0.313 0.546 Protein Intake Meeting needs 14.6 0 (0/13) Somewhat meeting needs 46.6 0 (0/22) Not meeting needs 13.5 8.3 (2/24) p 0.382 0.328

Vitamin B12, pg/ml Multi-Vitamin Mineral Supplement Intake Meeting needs 562.9 + 272.8 0 (0/30) Somewhat meeting needs 465.6 + 167.7 0 (0/22) Not meeting needs 540.3 + 229.2 4.6 (1/22) p 0.696 0.302 Protein Intake Meeting needs N/A 0 (0/16) Somewhat meeting needs N/A 0 (0/26) Not meeting needs N/A 3.2 (1/31) p 0.503

Ferritin, ng/ml Multi-Vitamin Mineral Supplement Intake Meeting needs 79.4 + 66.8 N/A Somewhat meeting needs 32.2 + 30 N/A Not meeting needs 25.5 + 19.2 N/A p 0.005

Anemic, g/dl; % Multi-Vitamin Mineral Supplement Intake 40

Average Value Incidence of Abnormal Value Nutrient 3-18 mo post-surgery 3-18 mo post-surgery Meeting needs 38.7 + 4.1 22.6 (7/31) Somewhat meeting needs 39.5 + 3.5 26.9 (7/26) Not meeting needs 36.6 + 3.8 60 (12/20) p 0.039 0.015 a Statistically different within supplement or protein intake groups, ANOVA for mean laboratory values, or Chi Square for the incidence of abnormal concentrations. b Mean ± SD. N/A=data not available

The average and minimum level of serum vitamin B12 did not significantly differ among the three levels of compliance with multivitamin intake following surgery (p = 0.295, p = 0.696, respectively). Although there was only one occurrence of vitamin B12 deficiency after surgery, it should be noted that this deficiency occurred in a patient who was recorded as non-compliant with multivitamin supplementation and protein intake. However, because of only once occurrence of vitamin B12 deficiency post-surgery this is not a statistically significant result for either differences in multivitamin or differences in protein intake (p = 0.302 and p = 0.503, respectively).

Although there was no significant difference in the average or minimum levels of folate among the three levels of compliance (p = 0.382, p = 0.385, respectively), the few folate deficiencies that did occur were present in the patient population deemed non-compliant with both multivitamin and protein intake. Ten percent of the patients who were non-compliant with multivitamin intake after surgery became folate deficient and 8.3% of the patients who were non- compliant with protein intake after surgery became folate deficient. Although this is notable, the difference between compliance levels is not significant (p = 0.126, p = 0.221, respectively).

There were no severe (< 2.5 mg/dl) or moderate (> 3.0 mg/dl) albumin deficiencies in both the protein and multivitamin groups that were recorded as compliant and at least somewhat compliant with intake. In addition, all severe albumin deficiencies occurred in patients who were deemed non-compliant with multivitamin and/or protein intake. Although neither of these 41 findings proves to be significant (p = 0.137 for differences in multivitamin intake and p = 0.604 for differences in protein intake), it still produces the trend that better compliance with multivitamins and protein intake following surgery produces less likelihood of developing a moderate or severe albumin deficiency.

There were significant differences in the minimum vitamin D3 level between patients recorded as compliant and somewhat compliant with multivitamins after surgery (p = 0.041).

There were no differences between levels of compliance with protein intake (p = 0.402). Despite significant differences among minimum vitamin D levels 3 - 18 months after surgery, the rate of vitamin D deficiency was not significant among compliance levels.

Minimum hemoglobin and hematocrit levels differed significantly between patients recorded as somewhat compliant and non-compliant with multivitamins after surgery (p = 0.044 and

0.039, respectively) as did the rate of developing anemia (p = 0.015). The percentage of anemia deficiency 3-18 months after surgery differed significantly among levels of multivitamin compliance (p = 0.015). Patients compliant with multivitamins had a 22.6% chance of developing anemia, 26.9% of patients somewhat compliant developed anemia, and 60% of patients non-compliant with multivitamins developed anemia.

Patients recorded as 1) compliant versus somewhat compliant and 2) compliant versus non- compliant with multivitamins after surgery had significantly different levels of minimum serum ferritin after surgery (p = 0.005). Therefore, being compliant with multivitamins after surgery had a significant impact on whether or not a patient became deficient in ferritin.

Table 14. Differences in nutritional deficiencies related to compliance with calcium supplementation

Incidence of Abnormal Value Average Value 3-18 mo post-surgery 3-18 mo post-surgery, % (n) 1,25 Dihydroxy Vitamin D, pg/ml Meeting needs 30.2 + 14.7a 64.3 (18/28) 42

Incidence of Abnormal Value Average Value 3-18 mo post-surgery 3-18 mo post-surgery, % (n) Somewhat meeting needs 17.6 + 7.6b 100 (8/8) Not meeting needs 27.3 + 9.6 60 (18/30) p 0.037 0.022 Calcium, mg/dl Meeting needs 9.2 + 0.4 3.0 (1/33) Somewhat meeting needs 9.1 + 0.4 11.1 (1/9) Not meeting needs 9.1 + 0.5 0 (0/36) p 0.949 0.165 Phosphorus, mg/dl Meeting needs 3.4 + 0.6 3.6 (1/28) Somewhat meeting needs 3.6 + 0.5 0 (0/7) Not meeting needs 3.4 + 0.7 5.9 (2/34) p 0.840 0.759 a Statistically different within groups categorized by calcium supplement intake; ANOVA for mean laboratory values, or Chi Square for the incidence of abnormal concentrations. b Mean ± SD

Patients recorded as non-compliant with calcium supplementation had significantly greater moderate D3 deficiency than other compliance levels (p = 0.022). Of patients deemed compliant with calcium supplementation, 10.7% were moderately D3 deficient. This is in contrast to

62.5% moderate D3 deficiency in patients who were somewhat compliant with calcium supplementation, and 23.3% moderate D3 deficiency in patients non-compliant with calcium supplementation. In addition, average vitamin D levels differed significantly among compliance groups 3 - 18 months after surgery.

There were no significant differences in vitamin A or vitamin D3 levels based on level of compliance with vitamin A & D supplementation following surgery. With the limited data available regarding vitamin A & D supplementation, levels of compliance were broken into only

2 groups; compliant with supplementation and non-compliant with supplementation. Although vitamin A and vitamin D2 levels did not differ by compliance with vitamin A & D 43 supplementation, albumin (p = 0.033), calcium (p = 0.024), potassium (p = 0.015), and thiamin

(p = 0.035) levels were significantly different between the two compliance levels.

Research Question 3: Are there Differences in Weight Loss Among Patients Receiving the RNY-

GB, BPD-DS, or VSG Procedures?

The following table shows the weight trends over time among the three different surgery types. The weight trend is documented in both pounds lost and % EBWL. There was very limited data available for all surgery types at the 18 month post-op periods.

Table 15. Comparison study of weight loss Length of Time Following Surgery 1 week 1 month 3 months 6 months 12 months

Excess Body Weight Loss % EBWL (n) VSG 11.9 + 6.2 (56) 18.9 + 6.2 (52) 32.0 + 10.0 (46) 42.9 + 12.6 (38) 46.3 + 14.8 (21) RNY-GB 11.6 + 6.0 (49) 18.9 + 6.2 (49) 35.3 + 10.8 (43) 51.7 + 13.9 (33) 59.7 + 12.9 (22) BPD-DS 12.4 + 8.9 (8) 21.2 + 10.4 (6) 39.6 + 9.1 (8) 64.1 + 8.2 (7) 70.9 + 7.6 (5)

Pounds Lost, lbs (n) VSG 19 + 10 (56) 31 + 12 (52) 48 + 17 (46) 66 + 21 (38) 70 + 27 (21) RNY-GB 20 + 11 (49) 32 + 11 (49) 59 + 19 (43) 103 + 84 (34) 104 + 32 (22) BPD-DS 24 + 16 (8) 44 + 24 (6) 72 + 22 (8) 116 + 29 (7) 149 + 65 (5) VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

As seen from the graphs below, % EBWL significantly increases over time within all three surgery groups (p < 0.0001). Additionally, the rate of increase in % EBWL over time is significantly different among all three surgery types (p = 0.0004). At six months post-surgery

(the period of time that includes the largest number of subjects) the % EBWL experienced in each surgery group is significantly different from the other two surgery groups (p < 0.0001). This means that the average amount of greatest weight loss experienced after surgery depends on which procedure was received. The greatest % EBWL experienced was for patients receiving the 44

BPD-DS (68.7%). The patients receiving the RNY-GB experienced the second largest % EBWL at 49.4% and patients receiving the VSG had the lowest % EBWL at 40.7%. The average maximum number of pounds lost after surgery was also significantly different among all three surgery types (139 pounds for BPD-DS, 115 pounds for RNY-GB, and 63 pounds for VSG).

Therefore, it can be determined that patients who receive the BPD-DS can expect the greatest weight loss and patients who receive the VSG can expect the lowest weight loss out of the three bariatric procedure.

Figure 4. Differences in pounds lost over time among the 3 different surgery types

a There was a significant difference over time, among surgeries and the interaction of time*surgery (p<0.0001), repeated measures ANOVA. VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

45

Figure 5. Differences in Percent Excess Body Weight Loss (%EBWL) over time among the 3 different surgery types

a There was a significant difference over time, among surgeries and the interaction of time*surgery (p<0.0001), repeated measures ANOVA. VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

Research Question 4: Are there Differences in the Incidence of Serious Complications Requiring

Hospitalization among Patients Receiving the RNY-GB, BPD-DS, or VSG Procedures?

Of the total 119 bariatric patients, 24 experienced complications that required hospitalizations. This equates to a total hospitalization rate of 20.2%. Complication rates per surgery type were: 32.2 % VSG, 50% RNY-GB, and 62.5% BPD-DS. Although the complication rate progressively increased as the type of procedure became more severe/malabsorptive, the difference in complications did not reach significance (p = 0.079).

Table 13 shows the different causes for complications after surgery per surgery type. Not all of these complications required hospitalizations. Reasons for hospitalizations included: IV therapy, cholecystitis, cholecystectomy, blood transfusions, strictures, recurrent nausea and vomiting, total parenteral or enteral feedings, and in one case reversal of the surgery. There was one death 46 that occurred during the RNY-GB surgery as a result of respiratory arrest causing diffuse cerebral edema and herniation into the forearm magnum.

Table 16. Complications following bariatric surgery a Surgery Types

Complications VSG RNY-GB BPD-DS Total # of Occurrences Abscess 1 1 0 2 Anal Fissure 1 1 0 2 Anemia 4 0 0 4 Blood Transfusion 1 1 0 2 Cholecystectomy 2 4 1 7 Conversion to Open Procedure 0 0 1 1 Death 0 1 0 1 Dehydration-IV Therapy 2 5 0 7 EGD 2 8 0 10 Extraluminal Bleed 1 0 0 1 Failure to Thrive 0 2 0 2 G –tube, decompression during Surgery 0 3 0 3 Gallstones 1 0 0 1 Gastrointestinal bleed 0 11 0 11 Gout 1 0 0 1 Hemorrhoids 2 1 0 3 Hernia with Repair 1 4 0 5 Infection/Sepsis 3 2 0 5 Kidney Stones 0 1 1 2 Obstruction 1 4 0 5 Rectal Bleed/ Diverticulitis 0 1 2 3 Recurrent Nausea/ Vomiting 6 15 0 21 Reversal of Surgery 0 1 0 1 Stage1Procedure 5 0 0 5 Stricture-balloon dilation 2 8 0 10 Total Parenteral Nutrition 1 3 0 4 Tube Feedings 0 1 0 1 Ulcer/Fistula 0 3 0 3 Weight Regain 1 3 0 4 Total Occurrences 38 84 5 127 a VSG, Vertical Sleeve Gastrectomy; RNY-GB, Roux-en-y Gastric Bypass; BPD-DS, Biliopancreatic Diversion with Duodenal Switch.

Sixteen patients had a single hospitalization, one patient had two hospitalizations, two had three and four hospitalizations, one patient had five hospitalizations, and two patients had seven hospitalizations over the 18-month study period. Mean hospitalization rates per surgery

47 were 1.75% for VSG, 3.0% for RNY-GB, and 1% for BPD-DS. These average hospitalization rates were not significantly different among surgery types (p = 0.240) despite the complication rate for RNY-GB being almost twice as high as the other surgeries complication rates. Even with removing the BPD-DS group for small sample size there was still no significant difference in hospitalization rates between the VSG and RNY-GB (p = 0.160). When looking at all of the hospitalizations as a group, there was no significant difference in the frequency of hospitalizations by surgery type (p = 0.875).

Morbidity in this study was defined as having either a hospitalization or significant complication after surgery during the 18-month study period. A total of 5 out of the 8 BPD-DS patients had morbidity (62.5%), 26 out of the 52 RNY-GB patients had morbidity (50%), and 20 out of the 59 VSG patients had morbidity (33.9%) following surgery. Although morbidity increases with the severity/malabsorption of the surgery, the difference in rates of morbidity is not significant among surgery types (p = 0.118).

Research Question 5: Are there Relationships Among Nutritional Deficiencies, the Amount of

Weight Loss, and Incidence of Serious Complications?

Both average nutritional indices and average minimum nutritional indices were evaluated when determining correlation between nutritional deficiencies and other variables such as amount of weight loss, serious complications, and number of visits with the registered dietitian and other health care professionals, etc. The labs focused on to determine nutritional deficiencies were albumin, transferrin, total cholesterol, hemoglobin, hematocrit, folate, and individual vitamin levels. The following summarizes these findings.

For albumin, there was a negative correlation between average levels and the number of hospitalizations after surgery. Therefore, as the average serum albumin level decreased, the

48 number of hospitalizations also increased (r = - 0.31, p = 0.008). This could mean that albumin deficiency correlates to more hospitalizations or that being hospitalized more often relates to having lower albumin levels. In contrast, when looking at minimum albumin levels, it was found that more visits with the dietitian after surgery was associated with a higher minimum albumin level (r = 0.24, p = 0.025). This could mean that more follow-up visits with the dietitian positively influence albumin levels and lessen the chances for protein-energy malnutrition. In addition, there was a positive correlation between number of RD visits before surgery and the average albumin level after surgery. Therefore, more frequent visits with the dietitian before surgery is associated with higher average albumin levels after surgery (r = 0.24, p = 0.041).

There was a negative correlation between maximum number of pounds lost after surgery and average cholesterol levels after surgery. This means that as the number of pounds lost increased, the average cholesterol level decreased (r = - 0.21, p = 0.031). In addition there was a negative correlation between minimum body weight after surgery and average HDL level after surgery. This means that as the average minimum body weight decreased, the average HDL level increased (r = - 0.21, p = 0.024). This could mean that more weight loss correlates to a greater risk of cholesterol deficiency and a higher HDL level. It does not appear that greater weight loss significantly influences, increases, or decreases other nutritional parameters following bariatric surgery.

Dietitians Visits and Weight Loss

There was a positive correlation between maximum % EBWL and number of dietitian visits after surgery. Therefore, the more frequently patient’s visit the dietitian after surgery the more likely they are to achieve greater % EBWL (r = 0.30, p = 0.002). There was a similar positive correlation between maximum number of pounds lost after surgery and number of

49 dietitian visits after surgery (r = 0.30, p = 0.002). There was an even stronger positive correlation between maximum number of pounds lost (r = 0.34, p = 0.0002) and maximum % EBWL (r =

0.53, p < 0.0001) and total meetings with healthcare professionals, which reinforces the benefit of follow-up after surgery to be successful with weight loss.

Weight Loss and Morbidity

It is interesting to note the correlation between significant complications/morbidity and maximum %EBWL/pounds lost. There is a negative correlation between morbidity and

%EBWL/ pounds lost (r = - 0.26/- 0.18, p = 0.005/0.050). There is also a negative correlation between significant complications and maximum pounds lost and % EBWL (r = - 0.27/- 0.19, p

= 0.003/0.041). This means that as significant complications and morbidity increases the number of pounds lost or % EBWL goes down. This is in fact, opposite of what was expected as this shows that less weight loss is associated with higher complication rates. However, it should be noted that more total meetings following surgery had a negative correlation to significant complications and morbidity (r = - 0.38/- 0.38, p < 0.0001/0.0001). Therefore, more frequent meetings following surgery means was associated with fewer significant complications.

Dietitians Visits and Nutritional Status

Registered dietitian visits did have some association with surgery outcomes. There was a positive correlation between dietitian visits before surgery and average thiamin level after surgery (r = 0.47, p = 0.009). Therefore, more RD visits before surgery positively impacted average thiamin levels after surgery. There was also a positive correlation between number of dietitian visits after surgery and average B12 levels after surgery (r = 0.28, p = 0.011). This means that the more RD visits after surgery, the higher the level of B12 after surgery, or a decreased risk of a vitamin B12 deficiency. Finally, there was a negative correlation between age

50 and vitamin D levels followings surgery (r = - 0.34, p = 0.003). This is noteable secondary to the higher incidence of vitamin D deficiency after surgery. From this finding it appears that the elderly bariatric patients are at greater risk of developing a vitamin D deficiency.

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CHAPTER V. DISCUSSION

Morbid obesity and associated health problems have increased at unprecedented rates over the past two decades. To date traditional methods of weight loss including diet modification, exercise, behavioral therapy, and pharmacotherapy remain ineffective at rates of

2.1 – 10 % EBWL over 2 years with continued behavioral intervention (23). Recently, it has even been suggested that one-third to two-thirds of dieters regained more weight than originally lost on their diets and that regardless of the amount of weight lost improvements in health were not consistently observed (24). However, the success of bariatric surgery in generating long-term weight loss and reducing comorbidities is well documented (5, 23). The following improvements have been noted following RNY-GB surgery: 64 – 100% resolution of diabetes, 25 – 100% show resolution of hypertension, 60 – 100% show resolution of dyslipidemias, 74-98% resolution of obstructive sleep apnea, 72-98% resolution of gastroesophageal reflux disease, and an 89% reduction in 5 year death rate (23).

Weight loss percents have been reported at 61.6% for RNY-GB, 47.5% for LAGB (26) over a 2-year period and 73 – 80% for BPD-DS (9) over a 9-month to 10-year period. Our weight loss findings were on par with this as we found 59.7% for RNY-GB, 46.3% for VSG

(purely restrictive procedure similar to LAGB), and 70.9% for BPD-DS after 1-year.

The downside is that bariatric surgery can also result in nutritional deficiencies and complications related to surgery. However, the risk of developing deficiencies and complications following bariatric surgery remain poorly studied, as do specific nutrient recommendations to prevent deficiencies. The most common deficiencies reported are B12 (12-33%), iron (49-52%), and vitamin A (50-70%) with B12 and iron more prevalent in RNY-GB and vitamin A more prevalent in BPD-DS. BPD-DS also carries greater risk of developing vitamin K, Zinc, and

52 vitamin D deficiencies (30). The BPD-DS patients in our study had a greater risk of developing folate (37.%), vitamin D (100%), and transferrin (83%) deficiency. However, the small sample size (n=8) of the BPD-DS group must be taken into account when interpreting these results. The

RNY-GB patients had a greater risk of developing anemia (50%).

The most common nutrient deficiencies among all surgery types were iron (34%), vitamin D

(66%), vitamin A (35%), and albumin (38%). There were too few vitamin E, vitamin K, and zinc values overall to produce good results or an accurate comparison among surgeries. It was found that B12 deficiency occurred in only 1.2% of patients within the 3-18 month time frame following surgery. Up to 36% of vitamin B12 deficiency has been observed in other studies (14-

15). Our low incidence may be related to the multivitamin that was recommended, which at it’s maximum dose gave 500 mcg of vitamin B12 daily and was to be started one week following surgery and continued long term. It was also found that the vitamin B12 deficiency occurred following the VSG and 4% of VSG patients had an occurrence of folate deficiency, where in previous studies no vitamin B12 or folate deficiencies occurred following restrictive procedures

(16).

Comparing the rate of nutrient deficiencies among restrictive and malabsorptive surgeries remains under-evaluated and the traditional rule of thought was that there were greater risks of developing nutrient deficiencies following malabsorptive procedures. In our research we found that there were surprisingly few differences in deficiencies between the RNY-GB and the VSG.

The only significant finding was that the RNY-GB patients had a greater risk of developing anemia following surgery. It was also notable that there was such a high overall rate of fat- soluble vitamins, even among of the restrictive VSG (20% vitamin A deficiency and 63% vitamin D), as this has not been documented in previous findings (29). In addition to this, we

53 found that the average vitamin D level after surgery among all surgery groups was below the normal reference range. The 66% deficiency rate of vitamin D was much higher than the 25.7% seen in previous studies (29). Unfortunately we were unable to measure vitamin D levels prior to surgery as only 18 patients had vitamin D levels drawn prior to surgery. Previous research has found vitamin D deficiency pre-operatively between 60-80% (30). This presents a great concern for morbidly obese patients, whether they are going through bariatric surgery or not.

Our results also support previous studies about the risk of calcium deficiency in purely restrictive versus malabsorptive procedures (17). We also found an absence of documented calcium deficiencies in the VSG group within the 3 - 18 months following surgery while there were documented calcium deficiencies in both the RNY-GB and the BPD-DS groups.

Thiamin deficiency was not often measured with frequency during the post-op time frame seen in our study (25% of patients were measured for thiamin deficiency), but from the limited results it appears that of the patients monitored 6.7% developed a thiamin deficiency. This is a higher rate than the 0.0002% seen in previous studies (14, 18). This difference could be due to the differing sample sizes and because thiamin levels in this stud were often only drawn secondary to patients experiencing complications such as frequent nausea and vomiting.

It should be noted that collection rates of overall vitamin levels were low, despite efforts to have patients undergo laboratory monitoring and follow-up visits postoperatively. This lack of compliance has been reported in previous studies as compliance rates of multivitamin/mineral supplementation average about 60% and that laboratory monitoring is often incomplete (27). We found an average of 66% of patients completed their 6-month post-op visit, 84.2% of eligible patients completed their 12-month follow up visits, and 37% of eligible patients completed their

18-month follow up visits. This is consistent with other studies as Lara et al found that

54 compliance for the 6 month follow up visit varied between 64.3% - 85.2% based on travel distance and the compliance for 9 month follow up visits varied between 35.7% - 70.3% (31).

These relatively low compliance rates surely play into outcomes following bariatric surgery, but how much so has not been determined.

We determined relationships among levels of compliance and outcomes following bariatric surgery. We recorded documented compliance with nutrient intake by the registered dietitian, physician’s assistant, or surgeon after surgery. The laboratory indices impacted from compliance with multivitamins were average ferritin and vitamin D levels. Lower compliance with multivitamins was associated with lower ferritin and vitamin D values. Noting concern over protein intake proved to be useful as noncompliance was associated with developing moderate or severe albumin deficiencies. Additionally, patients who were deemed less compliant with both multivitamin and protein intake were the same patients who developed folate and vitamin B12 deficiencies following surgery. Since compliance levels were recorded based on patient recall, compliance with protein and multivitamin/mineral supplementation may have been overestimated or underestimated.

We looked specifically at the role the RD played in patient outcomes after bariatric surgery.

Patients who had more visits with the dietitian after surgery experienced greater weight loss than those who had fewer visits with the dietitian after surgery. More dietitian visits were also associated with better thiamin and vitamin B12 values after surgery. This is evidence of the importance of follow-up after bariatric surgery.

Total hospitalization and complication rates following surgery were high. The hospitalization rate was 20.2% and complication rates per surgery type were: 32.2 % VSG, 50% RNY-GB, and

62.5% BPD-DS. This is in comparison to the complication rate of 39.6% within 180 days

55 following surgery (32). These complications and hospitalization rates do not differ significantly among surgery types despite differences in the severity of the surgery itself. In comparing groups there may have been inherent difference among the different surgery cohorts, as the type of surgery chosen depended on severity of symptoms, risk of complications, and amount of desired weight loss. Patients with severe complications in all of the surgery groups may have followed up more frequently than other patients, skewing the results for the total data, but not significantly impacting data when doing comparisons among surgery groups. It is the hope that better compliance with follow-up care may help to lower the risk of complications developing after surgery.

The retrospective study may also have some selection bias, as the patients who returned for follow-ups were the same patient’s who were compliant with supplementation and for whom the most data is available. Therefore, some of the low deficiency rates found in this study that do not correspond with previous studies may be due to high compliance rates in these patients.

There were several missing values from the analysis. This makes the sample size for some of the time periods smaller than others. Therefore, it is possible that some values show up to be significant in some time periods, but not in others due to sample size. In addition to chart notes being dependent on patient recall, there is also the fact that often chart notes were not thorough or were difficult to decipher. Because of this, some important data could have been missed. Additionally, it would have been ideal to have a longer follow-up period, but because of the time frame ALBSA was established, this was not a possibility. Patients were also given the option to have their laboratory values drawn from an outside facility. The problem with this is the increased risk of lost specimens and incorrect labeling, which may influence results.

Furthermore, some patients had their laboratory values drawn through their primary care

56 physician, and these results were not always forwarded on to ALBSA. We did not specifically measure reasons for being unable to obtain missing laboratory values.

Retrospective studies such as this one also have positive aspects. This study examines a true clinical situation, which means these results can be expected in a non-research setting. In addition only one investigator was used to collect and record the data, which helps with consistency of results. Finally, all patients within the study period were used so there were no results lost due to exclusion criteria.

The data obtained from this retrospective study produced other interesting conclusions.

Morbidly obese patients may be deficient in vitamin and mineral levels prior to ever having bariatric surgery, this was especially true for vitamin D levels as noted in previous studies, as well as MCV, anemia, albumin, and vitamin A levels. Anemia prior to surgery could have been related to iron, folic acid, or vitamin B12 deficiency. The commonality of observations about nutrient deficiencies prior to bariatric surgery is more proof that it is incorrect to believe excess weight is equated with appropriate or high vitamin and mineral levels. In reality, poor nutritional habits of morbidly obese patients may make them more likely to have lower levels of vitamins and minerals. There were very few correlations seen between extent of weight loss and the likelihood of developing nutrient deficiencies. However, it was interesting to note that greater weight loss was associated with improved HDL and total cholesterol levels.

Based on our finding we have the following recommendations to those who work bariatric surgery patients.

1 Vitamin and mineral levels should be drawn pre-operatively to identify and correct

nutritional deficiencies prior to bariatric surgery. Within this study, vitamin D, MCV,

57

hemoglobin or hematocrit, albumin, and vitamin A were the lab values most

frequently abnormal prior to surgery.

2 Even patients receiving purely restrictive procedures should receive routine testing

following bariatric surgery.

3 Long-term data needs to be evaluated to better determine risks and benefits of the

VSG.

4 Consideration to draw nutritional labs should be given to any morbidly obese patient.

5 Registered Dietitian visits before and after surgery show benefits in both weight loss

and nutritional status and should be considered as part of a comprehensive bariatric

program.

58

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