Eating Disorders.

Eating Disorders

Which of the following surgical weight loss procedures does not alter stomach hormone levels? (A) Gastric bypass (B) Gastric banding (C) Gastric pouch

Answer (B) Gastric banding

A patient presents 2 mo after gastric bypass surgery with vomiting, vision problems, and symptoms of ataxia. Which of the following nutrient deficiencies is most likely? (A) Thiamine (B) Zinc (C) Copper (D) Potassium

Answer (A) Thiamine

Patients with osteoporosis after gastric bypass surgery should be supplemented with calcium: (A) Bicarbonate (B) Citrate (C) Lactate (D) Gluconate

Answer (B) Citrate

Which of the following cannot be used to treat iron deficiency in patients who have had gastric bypass surgery? (A) Iron sucrose (B) Iron dextrose (C) Iron gluconate (D) Interferon

Answer (D) Interferon

What is the main cause of regain of weight after gastric bypass surgery? (A) Pouch enlargement (C) Development of binge eating disorder (B) Metabolic slowdown (D) Lack of physical activity

Answer (B) Metabolic slowdown

Choose the correct statement about the difference between constitutional thinness and anorexia. (A) Body mass index (BMI) is significantly higher in constitutional thinness (B) Body fat percentage is higher in anorexia (C) Leptin responds more acutely in constitutional thinness (D) Anorexic women are amenorrheic, while constitutionally thin women menstruate

Answer (D) Anorexic women are amenorrheic, while constitutionally thin women menstruate

Which of the following drugs is approved for use in bulimia
Which of the following drugs is approved for use in bulimia? (A) Paroxetine (B) Sertraline (C) Fluoxetine (D) Naltrexone

Answer (C) Fluoxetine

To prevent refeeding syndrome, _______ levels should be checked during the treatment of patients with anorexia. (A) Phosphorus (B) Potassium (C) Magnesium (D) Albumin

Answer (A) Phosphorus

Which of the following occurs in patients with bulimia
Which of the following occurs in patients with bulimia? (A) Amylase decreases (C) Bicarbonate decreases (B) Potassium decreases (D) Chloride increases

Answer (B) Potassium decreases

Choose the correct statement(s) about psychiatric therapy for bulimia and anorexia. (A) Cognitive behavioral therapy useful for bulimia (B) Behavior modification allows patients to focus on normalizing hunger and satiety (C) Body image dysfunction usually last to resolve (D) All the above

Answer (D) All the above

Among the following eating disorders, ________ is the most common
Among the following eating disorders, ________ is the most common. A) Anorexia nervosa B) Binge eating disorder C) Bulimia nervosa

Answer B) Binge eating disorder

Patients are most likely to seek treatment for: A) Anorexia nervosa B) Bulimia nervosa C) Binge eating disorder

Answer C) Binge eating disorder

Older patients with eating disorders most likely suffer from: A) Depression B) Anxiety C) Compromised self-worth D) All the above

Answer D) All the above

Most older patients with an eating disorder have _______ illness
Most older patients with an eating disorder have _______ illness. A) De novo B) Recurring

Answer B) Recurring

Which of the following patients meet(s) the qualifications for bariatric surgery? A) A woman 35 yr of age with a body mass index (BMI) of 40 B) A woman 35 yr of age with a BMI of 35, with diabetes and hypertension C) A and B

Answer C) A and B

Greater weight loss and better resolution of diabetes is achieved with which bariatric surgical procedure? A) Gastric bypass B) Lap band

Answer A) Gastric bypass

Nutritional deficiencies most often seen in patients who have undergone gastric bypass surgery include: Vitamin B12 Calcium Iron Folate A) 1,2 B) 2,3,4 C) 1,2,3 D) 1,2,3,4

Answer 1. Vitamin B12 2. Calcium 3. Iron C) 1,2,3

It is recommended that pregnancy be delayed _______ mo after bariatric surgery. A) 6 to 8 B) 10 to 12 C) 12 to 18 D) 24

Answer C) 12 to 18

All the following statements about bariatric surgery are correct, except: A) Gastric bypass is a restrictive procedure, while the lap band is a restrictive and malabsorptive procedure B) Eighty percent of patients who undergo bariatric surgery are women C) The mortality rate associated with gastric bypass is related to sex, age, and BMI D) The oral glucose challenge test should not be performed in pregnant patients who have undergone gastric bypass surgery

Answer A) Gastric bypass is a restrictive procedure, while the lap band is a restrictive and malabsorptive procedure

What is the name of the hormone that is produced in the stomach and creates a sense of hunger that is reduced after gastric bypass surgery and results in a reduced appetite and thus helps to produce weigh loss in the patients?

Answer Ghrelin

Bariatric surgery in children and adolescents
procedures on the rise as obesity rates in children and adolescents continue to climb, so do the number of bariatric surgeries performed. Studies have shown that more than half of pediatric patients who are obese carry their obesity into adulthood. With that in mind, it is not surprising that bariatric surgery among teens has quadrupled in recent years, increasing from an estimate of 200 procedures in the United States in 2000, to almost 800 procedures in 2003, according to data published in the Archives of Pediatric and Adolescent Medicine.

Bariatric surgery in children and adolescents
Despite the increase, the results of a 2007 study suggested that the risks for adolescents undergoing weight loss surgery are relatively low, and perhaps even lower than in adults, according to one of the researchers, Thomas H. Inge, MD, PhD, surgical director of the Comprehensive Weight Management Center at Cincinnati Children’s Hospital Medical Center. Thomas H. Inge, MD, PhD, has participated in several large-scale studies of the effects of bariatric surgery in obese adolescents. Although these results were promising, without long-term data regarding the effects of surgery on children and adolescents, many in the field have said the lasting consequences are unable to be fully understood. Perhaps the solution is the emergence of studies such as Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS), of which Inge is also the principal investigator. Teen-LABS is a large consortium made up of five clinical centers designed to determine the risks and benefits of gastric bypass bariatric surgery and compare them with adults. Endocrine Today interviewed leading researchers in the field to get their perspective on bariatric surgery in children and adolescents, such as preferred methods, psychological and legal issues, and other ongoing studies. All said they are aware of the Teen-LABS study. Inge said the results of the ongoing study will become available over the next few years, but important information, such as the documentation of severity of cardiovascular, endocrine, renal and psychosocial comorbidities in morbidly obese teens, were released at Obesity 2009, the Obesity Society’s annual meeting, in October. “What I hope we will see is that it makes a lot of sense to perform the surgery before comorbidities become irreversible,” Inge said.

Teen-LABS study Inge said the lack of information on bariatric research may be because there has not been a great deal of funding. However, the Teen-LABS study has garnered interest from the National Institutes of Health and is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. “The adult surgery is good for improving comorbidities of obesity, but there is good reason to believe that reversing morbid obesity early in life could more effectively reverse complications of obesity,” Inge said. In adults, bariatric surgery has shown prolonged weight control and improvement in serious obesity comorbidities. The two most commonly performed bariatric procedures in the United States are laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGB). The surgery may not be as effective if it is performed late in the course of comorbid conditions, which is why many have said it is a highly beneficial option for select teens. The Teen-LABS consortium began in June 2006, and in addition to Cincinnati’s Children’s Hospital Medical Center, it includes Texas Children’s Hospital in Houston, Children’s Hospital of Alabama in Birmingham, University of Pittsburgh Medical Center and Nationwide Children’s Hospital in Columbus, Ohio. Teen-LABS is structured similar to the Longitudinal Assessment of Bariatric Surgery, established previously by the NIDDK. The Teen-LABS study is examining standard clinical care of 200 adolescents aged 19 years and younger undergoing bariatric surgery. In addition to the risks of bariatric surgery for adolescents, Teen-LABS will examine CV risk factors, fitness, endocrine changes, sleep disorders, weight loss and body composition, renal disease, liver function and size, nutrition deficiencies, adherence to nutritional supplements and psychosocial factors. Inge said one of the interesting results to come from the study is learning what comorbidities bariatric teens have, some of which have not been described before. “For instance, we’re looking at the kidneys; not a lot is known about the effect of extreme adolescent obesity on renal function. And what we are finding in our early results is that there are very real and present signs of kidney dysfunction in teens with morbid obesity,” he said. Inge said that he and his co-investigators are committed to following the Teen-LABS cohort for a decade, and objectively documenting outcomes; this would require extended funding past the 2006 to 2012 initial funding period — giving an even longer term look after the surgery. “It’s great to see this type of support for this research,” Inge said.

Support for bariatric surgery
Fernando B. Bonanni Jr., MD, director of the Institute for Metabolic and Bariatric Surgery at Abington Memorial Hospital, Pennsylvania, said bariatric surgery in adolescents was once a hot topic in the field, but it is beginning to simmer down. Fernando B. Bonanni Jr. “There is no question that adolescents enjoy all the benefits of bariatric surgery,” Bonanni said, adding that the reduction of comorbidities is the greatest selling point. “Moreover, for adolescents, the psychosocial benefits are life changing. Like any other surgery, an adolescent will fare better with regard to handling the surgery.” The benefit of youth is that patients will have fewer comorbid problems going into the surgery. If they have comorbid diseases, they have had them for less time. “Chronic diseases, like diabetes, take its toll on a person, especially an obese patient. We must remember that the real problem with obesity is that our body systems are equipped with reserves to handle disease and injury. If you are 100 lb or more overweight, your system is working for two people or more,” Bonanni said. It is for this reason that adult obese patients are more likely to develop diseases and conditions at a higher incidence, such as type 2 diabetes, he said. Inge was an investigator of a 2009 multicenter study that found teens who underwent gastric bypass surgery showed “dramatic, often immediate” remission of type 2 diabetes. Teens who underwent LRYGB lost, on average, one-third of their body weight, and remission of diabetes was induced in all but one teen. In most cases, patients stopped taking their diabetes medications by the time they left the hospital. “The results have been quite dramatic, and, to our knowledge, there are no other antidiabetic therapies that result in more effective and long-term control than that seen with bariatric surgery,” Inge said. He noted that the patients also showed significant improvement in blood pressure, insulin, glucose, cholesterol and triglyceride levels.

Impact of surgery Nicole M. Chandler, MD, a pediatric surgeon at All Children’s Hospital, St. Petersburg, Fla., said although the technique of bariatric surgery and its immediate postoperative care is identical in the pediatric and adult populations, the adolescent population has unique metabolic and psychological demands. “It is important that ongoing nutritional and psychological support is provided to this younger age group and long-term follow-up is provided far into adulthood,” Chandler said. It is difficult to assess the effect that bariatric surgery may have on the lives of adolescents and their family. “While surgical options may provide sustained weight loss and resolution of comorbid diseases, they also carry potentially life-threatening complications, the need for continued life-long compliance with eating and behavioral modifications, and uncertain long-term problems decades after the operation,” Chandler said. Bonanni said herein lies the controversy with bariatric surgery in adolescents. “The question is not: Will they do well with surgery,” he said. “There is no question they do better than adults; however, the problem lies in the fact that adolescents have not suffered from comorbid problems for a prolonged period. Therefore, they sometimes do not realize and appreciate the benefit of the weight loss. This sometimes leads to complacency when it comes to the life changes that are required to succeed long term. This includes exercise, supplemental vitamins, portion control and good eating habits.” It is important that adolescents participate in a rigorous preoperative screening that includes educational information and how to manage expectations. The program they enter should require adolescents to attend support group sessions. “Most importantly, the patient’s family must be actively engaged in the entire process. In adolescents, the support system they rely on is paramount to their success. This is a support system that unfortunately in many cases is already broken and needs repair. A good program for surgical weight loss will take all of this into consideration,” Bonanni said.

Legal and ethical dilemmas
Although there are benefits to bariatric surgery, the procedure is still a major surgery that has long-reaching consequences, said Brian M. Fidlin, PsyD, program director of the NEW (Nutrition, Exercise and Weight Management) Kids Program at Children’s Hospital of Wisconsin. “There are questions that remain about whether a younger individual possesses the maturity to make such a decision,” Fidlin said. He said not all insurance plans consider bariatric surgery a viable option for adolescents; in addition, many of these younger individuals may be dropped from their parents’ insurance plans at some point. “One of the major risks is determining if this adolescent and his or her support system will be capable of making and maintaining the necessary changes to promote a weight loss. It is essential that an individual understand the procedure, risks and benefits, as well as postsurgical requirements,” Fidlin said. Evan P. Nadler, MD, co-director of the Obesity Institute at Children’s National Medical Center in Washington, D.C., said there are many legal and ethical issues with adolescents and bariatric surgery. “Firstly, [LAGB] is not yet FDA-approved for children younger than 18 years of age — so the safest option isn’t even approved for children/adolescents,” said Nadler, a leading researcher of bariatric surgery in adolescents. “So it’s an ethical question: Do you perform a safe procedure or make a 300-lb 15-year-old with diabetes wait another year or two until the band gets approved?” He said it is not a question that is easily answered. “My personal feeling is that it’s less ethical to withhold a procedure that you know can help, than it is to perform a procedure that doesn’t necessarily have long-term studies to prove its durability,” Nadler said.

Effectiveness of LAGB Nadler was an investigator of a 2007 NYU Medical Center study that showed LAGB to be an effective procedure to combat obesity in adolescents. The study was the first to evaluate LAGB in patients younger than 17 and revealed that patients on average lost about 50% of their excess weight by one year after surgery. The surgery was performed on 53 morbidly obese adolescents aged between 13 and 17, and, in addition to the weight loss, none of the patients regained any of the weight. Complications were found to be significantly less severe with LAGB, as well. Nadler said the results of the study suggest that LAGB provides a safer and equally effective weight loss compared with LRYGB. George Woodman, MD, medical director of the Baptist Weight Loss Center in Memphis, Tenn., agrees. “In general, I would not consider a gastric bypass on an adolescent. This is an excellent procedure, but one that is not reversible. The lap band and gastric sleeve procedures, I believe, are a much better option,” Woodman said, citing that LAGB is reversible and has been documented to be safe in many studies. “The sleeve procedure, although not reversible, is safer than a bypass and does not have the same complication possibilities. The stomach is made smaller, but the intestines are not ‘rearranged.’ Therefore, absorption is normal, and the procedure is less morbid,” he said.

Paucity of data Saurabh Khandelwal, MD, an acting assistant professor at the Center for Videoendoscopic Surgery in the department of surgery at the University of Washington, Seattle, said bariatric surgery in the adolescent population is still a controversial topic because of the lack of data. For example, Khandelwal said performing LRYGB in children and adolescents may cause potentially harmful effects on development and growth and affect physical maturation. Saurabh Khandelwal “Long-term data, at this time, do not exist that can give insight into outcomes from procedures such as the gastric band or sleeve gastrectomy. We don’t know the long-term consequences of placing a band in an adolescent, in which case he or she may have it for 60 years or longer,” Khandelwal said. “Young patients undergoing such procedures should be carefully followed and assessed, preferably through participation in studies.” However, despite the lack of data, Nadler said studies such as the Teen-LABS gastric bypass study and the NYU gastric banding study show that weight loss is as good if not better than the similar procedures in adults. “And the procedures are as safe — if not safer — in adolescents,” Nadler added. “I personally believe that 10 to 20 years from now, there will be as many teenagers getting bariatric surgery as adults, especially since they do likely have better outcomes,” he said. More studies are needed on the topic, and Nadler plans to investigate the topic further in his program at Children’s National Medical Center. Almost all of the researchers Endocrine Today spoke with viewed bariatric surgery as a means for helping obese adolescents. “Bariatric surgery is not a magic bullet,” Bonanni said. “It is a tool. If you do not take the tool out of the shed, it will not work for you.” – by Angelo Milone

The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population Abstract Background Fatty liver (FL) is the most frequent liver disease in Western countries. We used data from the Dionysos Nutrition & Liver Study to develop a simple algorithm for the prediction of FL in the general population. Methods 216 subjects with and 280 without suspected liver disease were studied. FL was diagnosed by ultrasonography and alcohol intake was assessed using a 7-day diary. Bootstrapped stepwise logistic regression was used to identify potential predictors of FL among 13 variables of interest [gender, age, ethanol intake, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase (GGT), body mass index (BMI), waist circumference, sum of 4 skinfolds, glucose, insulin, triglycerides, and cholesterol]. Potential predictors were entered into stepwise logistic regression models with the aim of obtaining the most simple and accurate algorithm for the prediction of FL. Results An algorithm based on BMI, waist circumference, triglycerides and GGT had an accuracy of 0.84 (95%CI 0.81–0.87) in detecting FL. We used this algorithm to develop the "fatty liver index" (FLI), which varies between 0 and 100. A FLI < 30 (negative likelihood ratio = 0.2) rules out and a FLI ≥ 60 (positive likelihood ratio = 4.3) rules in fatty liver. Conclusion FLI is simple to obtain and may help physicians select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. Validation of FLI in external populations is needed before it can be employed for these purposes.

The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population BMC Gastroenterology 2006, 6:33doi: / X-6-33 Teh electronic version of this article is the complete one and can be found online at: Received:16 August 2006Accepted:2 November 2006Published:2 November 2006© 2006 Bedogni et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background Fatty liver (FL) is the most frequent liver disease in Western countries [1-4]. Obesity and its complications, especially type 2 diabetes and hypertriglyceridemia, are likely to be the main responsible of the current epidemic of FL, while ethanol intake may play a minor role [5-7]. In a nested case-control study of the Dionysos Project, we found that body mass index (BMI) was a stronger risk factor for FL than ethanol intake in the general population of Northern Italy [6]. Interestingly, this finding was confirmed by a recent study performed in China [8]. Waist circumference has long been hypothesized to be a predictor of FL independently from BMI, but data for the general population were not available until very recently [1,8]. Because BMI is a surrogate index of body adiposity [9], direct indexes of adiposity such as skinfolds can be of value when studying the relationship between body fatness per se and disease [10,11]. Hyperinsulinemia and insulin resistance are common in subjects with FL independently from BMI and thus are expected to be markers of FL in the general population [12]. Despite the operational separation of FL into alcoholic and non-alcoholic fatty liver disease (NAFLD) [4], the relative contribution of ethanol intake and other factors in the pathogenesis of FL is still uncertain [3]. Using data collected during the Dionysos Nutrition & Liver Study [1], we evaluated the contribution of ethanol intake, anthropometry, liver enzymes and metabolic parameters to the risk of FL and developed an algorithm for the prediction of FL in the general population.

Study design The protocol of the Dionysos Nutrition & Liver Study was described in detail elsewhere [1]. Briefly, of 5780 residents of Campogalliano (Modena, Italy) aged 18 to 75 years, 3345 (58%) agreed to participate to the study; 3329 (99%) of them had all the data required by the Dionysos Project[7,13] and were considered for further analysis. 497 (15%) of them had suspected liver disease (SLD) according to at least one of the following criteria: 1) alanine transaminase (ALT) > 30 U*L-1; 2) gamma-glutamyl-transferase (GGT) > 35 U*L-1; 3) presence of hepatitis B surface antigen (HBsAg); 4) presence of Hepatitis C (HCV) virus ribonucleic acid (RNA) after detection of anti-HCV antibodies. The 497 subjects with SLD were matched with an equal number of subjects of the same age and sex but without SLD, randomly selected among the remaining 2832 subjects. After exclusion of subjects with HBV or HCV infection, the original analysis was performed on 224 subjects with and 287 without SLD [1]. The present analysis is performed on 216 (96%) subjects with and 280 (97%) without SLD, based on the availability of skinfold measurements.

Methods Besides a clinical and laboratory evaluation, each subject underwent a liver ultrasonography, an anthropometric assessment and a 7-day diary of food intake (7DD) [1]. HBsAg and anti-HCV antibodies were assessed and subjects with anti-HCV antibodies underwent an HCV-RNA assessment to confirm HCV infection [1,14]. ALT, aspartate transaminase (AST), GGT, glucose, triglycerides and cholesterol were measured by standard laboratory methods after 8-hr fasting. Insulin was measured by radio-immuno-assay (ADVIA Insulin Ready Pack 100, Bayer Diagnostics, Milan, Italy), with intra- and inter-assay coefficients of variation < 5%. FL was diagnosed by the same operator at ultrasonography [6]. Weight, stature, circumferences (waist and hip) and skinfolds (triceps, biceps, subscapular and suprailiac) were measured by two trained dietitians who had been standardized before and during the study according to standard procedures [15]. Body mass index (BMI) was calculated as weight (kg)/stature (m)2 and the sum of 4 skinfolds by summing triceps, biceps, subscapular and suprailiac skinfolds [16,17]. The 7DD was administered to the subjects by two trained dietitians, who discussed it with the subject when she/he returned it one week later [18]. To avoid the confounding effect of seasonality on food intake, the 7DD diary was administered to a similar number of patients with and without SLD each month [19]. Mean daily ethanol intake was calculated as the mean value of ethanol intake as assessed by the 7DD[20]. The study protocol was approved and supervised by the Scientific Committee of the Fondo per lo Studio delle Malattie del Fegato (Trieste, Italy), and all subjects gave their written informed consent to participate.

Statistical analysis Continuous variables are given as medians and interquartile ranges (IQR) because of skewed distributions. Comparisons of continuous variables between subjects with and without FL were performed with the Mann-Whitney test and those of nominal variables with the Fisher's exact test. To identify candidate predictors of FL, we performed a stepwise logistic regression analysis on 1000 bootstrap samples of 496 subjects (probability to enter = 0.05 and probability to remove = 0.1) [21]. All variables besides gender were evaluated as continuous predictors. Linearity of logits was ascertained using the Box-Tidwell procedure [22]. To obtain a linear logit, we transformed age using the coefficient suggested by the Box-Tidwell procedure [(age/10) 4.9255] and ALT, AST, GGT, insulin and triglycerides using natural logarithms (loge). The logits of the other predictors (BMI, waist circumference, glucose, cholesterol, ethanol and the sum of 4 skinfolds) were linear. Candidate predictors identified at bootstrap analysis were evaluated using three stepwise logistic models before obtaining a final prediction model (probability to enter = 0.01 and probability to remove = 0.02; these more stringent levels were used to protect against type I errors). The goodness of fit of the models was evaluated using the Hosmer-Lemeshow statistic and their accuracy was assessed by calculating the non-parametric area (AUC) under the receiver-operating curve (ROC) with 95% confidence intervals (95%CI) [23,24]. The standard errors of the regression coefficients of the final model were calculated using 1000 bootstrap samples of 496 subjects. The probabilities obtained from the final model were multiplied by 100 to obtain the fatty liver index (FLI). The sensitivity (SN), specificity (SP), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of 10-value intervals of FLI were calculated [23]. Statistical analysis was performed using STATA 9.2 (StataCorp, College Station, Texas, USA).

Results Table 1 gives the characteristics of the subjects with and without FL. FL was more frequent among males than females (54 vs. 34%). Age, ethanol intake and cholesterol did not differ between subjects with and without FL. On the contrary, ALT, AST, GGT, BMI, waist circumference, the sum of 4 skinfolds, glucose, insulin and triglycerides were significantly higher in subjects with than in those without FL. Table 1. Measurements of subjects with and without fatty liver. Figure 1 (Model 1) gives the number of times each of the 13 variables of interest was selected by bootstrapped stepwise logistic regression. The predictors identified most frequently were insulin (93%), triglycerides (91%), BMI (78%), gender (77%), GGT (77%) and age (64%). When these 6 predictors were entered into the stepwise model, age did not remain in the model (p = ; model not shown). The model based on the remaining 5 predictors fitted well (p = , Hosmer-Lemeshow statistic) and had a ROC-AUC of 0.85 (95%CI 0.82–0.89; model not shown).

Table 1: Measurements of subjects with and without fatty liver.
FL (n = 228) No FL (n = 268) p Gender (male/female, n) 164/64 141/127 <0.0001 Age (years) 58 (17) 57 (26) Ethanol (g*day-1) 13 (35) 11 (28) ALT (U*L-1) 27 (21) 19 (16) <0.0001 AST (U*L-1) 22 (10) 20 (8) GGT (U*L-1) 31 (35) 19 (14) <0.0001 BMI (kg*m-1) 29.5 (5.8) 25.7 (4.1) <0.0001 Waist circumference (cm) 98 (16) 86 (14) <0.0001 Sum of 4 skinfolds (mm) 74.1 (37.4) 59.6 (26.8) <0.0001 Glucose (mg*dL-1) 96 (18) 89 (13) <0.0001 Insulin (mU*L-1) 9 (8) 5 (4) <0.0001 Triglycerides (mg*dL-1) 141 (102) 91 (60) <0.0001 Cholesterol (mg*dL-1) 219 (57) 212 (52) Values are medians and interquartile ranges for continous variables and number of subjects for categorical variables. Abbreviations: FL = fatty liver; p = p-value (Mann-Whitney U-test for continuous variables and Fisher's Exact test for categorical variables); ALT = alanine transaminase; AST = aspartate transaminase; GGT = gamma-glutamyl-transferase; BMI = body mass index.

Figure 1 Selection of candidate predictors at bootstrapped stepwise logistic regression Selection of candidate predictors at bootstrapped stepwise logistic regression. Bars indicate the number of times out of 1000 that the variables were selected for inclusion in 3 models. Model 1 is the starting model, Model 2 removes insulin and Model 3 removes skinfolds. Data are sorted using Model 3. Abbreviations: * = transformed using natural logarithm; ** = transformed using Box-Tidwell transformation (see text for details); other abbreviations as in Table 1.

Table 2: The parameters of the fatty liver index (FLI).
β SE (β) STD (β) p Loge (triglycerides, mg*dL-1) <0.0001 BMI (kg*m2-1) Loge (GGT, U*L-1) <0.0001 Waist circumference (cm) Constant <0.0001 Abbreviations: β = regression coefficient; SE = standard error; STD = standardized value; loge = nathural logarithm. Other abbreviations as in Table 1. FLI is calculated by multiplying the predicted probabilities per 100 (see text for the formula).

Results Since insulin is not routinely measured, we tested whether its removal from the model would decrease the accuracy of the estimate. After exclusion of insulin, the predictors most frequently identified were triglycerides (100%), GGT (80%), BMI (79%), ALT (70%), the sum of 4 skinfolds (68%) and gender (67%) (Figure 1, Model 2). When these 6 predictors were entered into the stepwise model, ALT did not enter it (p = ; model not shown). The model based on the 5 remaining predictors fitted well (p = , Hosmer-Lemeshow statistic) and had a ROC-AUC of 0.85 (95%CI 0.81–0.88; model not shown). Since skinfolds are not routinely measured, we tested whether their removal from the model would decrease the accuracy of the estimate. After exclusion of the sum of 4 skinfolds, the predictors identified most frequently were triglycerides (100%), BMI (95%), ALT (77%), GGT (73%) and waist circumference (58%) (Figure 1, Model 3). When these 5 predictors were entered into the stepwise model, ALT did not enter it (p = ; p to remove = ; model not shown). The model based on the remaining 4 predictors fitted well (p = , Hosmer-Lemeshow statistic) and had a ROC-AUC of 0.85 (95%CI 0.81–0.88; model not shown). A comparison of the ROC-AUCs of Models 2 (p = ; Bonferroni's correction) and 3 (p = )vs. Model 1 revealed no difference so that we choose Model 3 for further analysis. The bootstrapped regression coefficients of Model 3 are given in Table 2. We multiplied the probabilities generated by Model 3 per 100 to obtain a score comprised between 0 and 100, which we call the "fatty liver index" (FLI). FLI is thus calculated as:

Fatty Liver Index FLI = (e 0.953*loge (triglycerides) *BMI *loge (ggt) *waist circumference ) / (1 + e 0.953*loge (triglycerides) *BMI *loge (ggt) *waist circumference ) * 100 As shown by the standardized regression coefficients, the greatest contribution to the prediction of FL came from waist circumference, followed by BMI, triglycerides and GGT. Table 3 gives the SN, SP, LR+ and LR- for 10-unit intervals of FLI. A FLI < 30 can be used to rule out (SN = 87%; LR- = 0.2) and a FLI ≥ 60 to rule in hepatic steatosis (SP = 86%; LR+ = 4.3).

Table 3: Diagnostic accuracy of the fatty liver index.
FLI cut-point % SN SP LR+ LR- ≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥ Abbreviations: FLI = fatty liver index; % = number of patients with FLI ≥ cut-point; SN = sensitivity; SP = specificity; LR+ = positive likelihood

Discussion We used data from the Dionysos Nutrition & Liver Study to develop a simple algorithm for the prediction of FL. Age was not associated with FL in any of the multivariable models while gender lost its association with FL after exclusion of insulin and skinfolds. Ethanol intake was not associated with FL in any of the models. Thus, at least at the values of intake observed in the Dionysos Nutrition & Liver Study, ethanol is not a risk factor for FL in the general population of Northern Italy. Waist circumference and BMI were the strongest predictors of FL in the final model. Together with the lack of association of FL with ethanol intake, this finding strongly supports the hypothesis that obesity is the main responsible of the current epidemic of FL [1,4,6]. It is of some interest that waist circumference did not add to the prediction of FL when skinfolds were in the model but, from a practical viewpoint, there is no need to measure skinfolds for predicting FL. Among liver enzymes, only GGT was an independent predictor of FL while AST was not associated with FL in any of the models and ALT was not an independent predictor of FL. We have previously shown that ALT is not a surrogate marker of NAFLD and the present study extends this consideration to the entire spectrum of FL disease [1]. Insulin was the predictor most frequently selected for inclusion in Model 1 and was the second most important predictor after BMI in the same model (data not shown). Thus, we confirm that insulin is an independent risk factor for FL in the general population [12]. It is of some interest that waist circumference did not add to the prediction of FL when insulin was in the model but that it was the strongest predictor of FL in the final model. This cannot be easily explained by the known association between waist and insulin (resistance) because BMI is similarly correlated with this latter [25,26] as also observed in this study (data not shown). Triglycerides were independent predictors of FL in all models, confirming our previous findings [16]. Glucose and cholesterol were not predictors of FL even if it may be noticed that the selection of glucose as potential predictor increased after exclusion of insulin from the model. The main limitations of the Dionysos Nutrition & Liver Study are the suboptimal respondent rate (58%) and the fact that ultrasonography cannot detect steatohepatitis (SH) [1]. This latter diagnosis can be obtained only by biopsy and, because of obvious ethical reasons, a SH score will never be available in a representative sample of the general population [3]. Scores developed in clinical series may be used for this purpose but they have not been tested in the general population [27,28].

Conclusion The "fatty Liver index" (FLI) we developed is accurate and easy to employ as BMI, waist circumference, triglycerides and GGT are routine measurements in clinical practice [7,29,30]. In our population, a FLI < 30 ruled out and a FLI ≥ 60 ruled in hepatic steatosis as detected by ultrasonography. Potential clinical uses of FLI include the selection of subjects to be referred for ultrasonography and the identification of patients for intensified lifestyle counseling [30,31]. On the research side, FLI may be used to select subjects at greater risk of FL for planning observational or interventional studies [30,32]. Even though, for reasons of biological plausibility and coherence with previous studies [5,6,8], we expect that the parameters employed by FLI will be predictors of FL in Western countries besides Italy, it is very important that FLI be validated in external populations before it is employed in practice.

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45th Annual Meeting of the European Association for the Study of Diabetes
High levels of fatty liver index (FLI) were associated with increased insulin resistance, carotid intima-media thickness and coronary heart disease risk in middle-aged people without diabetes, according to new data presented here. Using data from the European RISC study (n=1,308), researchers in Italy evaluated a variety of cardiometabolic risk factors, including fatty liver index, metabolic profile, glucose tolerance, peripheral insulin sensitivity, hepatic insulin resistance, beta cell function, physical activity, CHD risk and early carotid atherosclerosis. FLI is a new index recently proposed as a predictor of the presence of fatty liver, which includes in its formula waist circumference, BMI and triglycerides, Amalia Gastaldelli, PhD, metabolism unit, Fondazione Toscana G. Monasterio and CNR Institute of Clinical Physiology, Pisa, Italy, told Endocrine Today. FLI >60 is equal to a greater than 78% presence of fatty liver whereas FLI <20 is equal to a greater than 91% absence of fatty liver, she said.

45th Annual Meeting of the European Association for the Study of Diabetes
The first goal was to validate FLI as a predictor of hepatic steatosis, and the second goal was to determine if FLI score .60 could predict metabolic alterations and presence of atherosclerosis. In a separate group of people (n=37), hepatic fat content was measured using magnetic resonance spectroscopy. Comparison revealed that FLI and hepatic fat percentage were well correlated, according to the researchers. People with FLI <20 had no hepatic fat (range, 0.4% to 4.2%; n=6) whereas those with FLI >60 had steatosis (range, 8.6% to 24%; n=10). In the RISC cohort, people with FLI scores >60 had higher fasting concentrations of glucose, insulin and LDL, and reduced concentrations of HDL, compared with those with index scores <20. Moreover, they had higher blood pressure, were more insulin resistant at the whole body level and in the liver, and had impaired beta cell glucose sensitivity, Gastaldelli said. Overall, the RISC cohort was at low risk for CHD — 9% were at medium-to-high risk and 83% were at below average risk. The 10-year CHD score was positively associated with BMI and waist circumference, but negatively associated with physical activity and peripheral insulin sensitivity. The researchers reported a strong association between FLI and CHD. Intima-media thickness was low, on average, in the cohort (0.60 mm), and was positively associated with age, BMI, waist circumference, systolic BP, LDL and fasting plasma glucose; it was negatively associated with HDL, physical activity, peripheral insulin sensitivity and FLI (P<.0001) for all. Higher values of intima-media thickness were also associated with increased CHD and fatty liver scores. Independent predictors of intima-media thickness included peripheral insulin sensitivity, age, systolic BP, LDL and gender, according to multivariate analysis. When FLI was added to the multivariate model, it replaced peripheral insulin resistance (P=.0001). “Calculation of FLI from simple metabolic and anthropometric data can be a useful parameter to assess cardiometabolic risk,” Gastaldelli said. – by Katie Kalvaitis

Simple Index Helps Identify Fatty Liver
May 5, 2006 (Vienna) — A score derived from 5 easy-to-measure parameters can be used clinically to help identify patients with fatty liver disease, according to Italian researchers. The tool should help general practitioners and other physicians diagnose this underreported condition, which otherwise requires ultrasound for its identification. According to senior investigator Giorgio Bedogni, MD, "Fatty liver is the most [common] liver disease in Western countries" and is often seen in combination with metabolic syndrome. "A diagnostic algorithm developed in the general population may help general practitioners to diagnose [it]." Dr. Bedogni is an internist and coordinator of the Clinical Epidemiology Unit at the Liver Research Center, University of Trieste, Italy. He is also an adjunct professor of statistics in medicine at the School of Nephrology & Dialysis, Modena and Reggio Emilia University, Italy. Elisabetta Bugianesi, MD, PhD, who was not involved in the study, agrees that nonalcoholic fatty liver disease (NAFLD) in particular is an important clinical entity that can be difficult to identify. "NAFLD constitutes a special challenge for physicians for several reasons: any distinction between nonprogressive (fatty liver) and progressive disease (nonalcoholic steatohepatitis [NASH]) is only based on liver histology, but NAFLD patients are generally asymptomatic [so] invasive procedures are not easy to propose [or] to accept," she told Medscape via . "Surrogate markers (mainly alanine aminotransferase) are not universally accepted, and a large body of evidence indicates that progressive liver disease may also be present in subjects with normal enzyme levels," Dr. Bugianesi pointed out. "Hence, identification of scientifically compelling noninvasive markers is eagerly awaited." Long-term complications of NAFLD include cirrhosis and hepatocellular carcinoma. Dr. Bugianesi is a professor of gastroenterology and an expert in NAFLD from the Division of Gastro-hepatology, University of Torino, Italy. In an effort to develop a simple method for identifying patients who may have fatty liver disease, Dr. Bedogni and colleagues used data from the Dionysos Nutrition and Liver Study to determine the degree to which drinking habits, anthropometry, and metabolic parameters contribute to the risk for the condition in 216 patients with suspected liver disease but no hepatitis B and C infection as well as in 280 age- and sex-matched controls. All participants were from the same town in northern Italy. The presence of fatty liver disease was confirmed via ultrasonography. Results were presented here by Vittorio di Maso, MD, another researcher at the Liver Research Center, at the 41st annual meeting of the European Association for the Study of the Liver (EASL). "Body mass index and waist circumference are independent predictors of fatty liver in the general population, while ethanol intake and alanine transaminase [levels] are not," Dr. Bedogni told Medscape in an . "A [Fatty Liver Index or FLI] score obtained from 5 parameters — gender, gamma-glutamyl-transferase, body mass index, waist circumference, and triglycerides — may be used to rule out fatty liver when 1.0 [or less, negative likelihood ratio = 0.2] and rule it in when [the score is at least] 3.0 [positive likelihood ratio = 4.4].... This score was developed on a representative sample of the general population of a town of Northern Italy and as such is ideal for use by general practitioners." The authors conclude that patients' FLI could be used to determine who requires a confirmatory ultrasound and/or counseling to reduce weight or improve other clinical risk factors for complications. According to Dr. Bugianesi, "This index may help primary care physicians to identify NAFLD, especially in high-risk subjects, and may help to increase the public awareness of NAFLD." Its only major limitation is that it cannot determine the type of fatty liver disease present. To date, she says, only liver biopsy can reliably do so. EASL 2006: Abstract 676. Presented April 27, 2006.

Nonalcoholic fatty liver disease (NAFLD)
INTRODUCTION — Nonalcoholic fatty liver disease (NAFLD) is a clinico-histopathological entity with histological features that resemble alcohol-induced liver injury, but by definition, occurs in patients with little or no history of alcohol consumption. It encompasses a histological spectrum that ranges from fat accumulation in hepatocytes without concomitant inflammation or fibrosis (simple hepatic steatosis) to hepatic steatosis with a necroinflammatory component (steatohepatitis) that may or may not have associated fibrosis. The latter condition, referred to as nonalcoholic steatohepatitis (NASH), may progress to cirrhosis in up to 20 percent of patients [1]. NASH is now recognized to be a leading cause of cryptogenic cirrhosis [2]. The pathogenesis of nonalcoholic fatty liver disease has not been fully elucidated. The most widely supported theory implicates insulin resistance as the key mechanism leading to hepatic steatosis, and perhaps also to steatohepatitis. Others have proposed that a "second hit," or additional oxidative injury, is required to manifest the necroinflammatory component of steatohepatitis. Hepatic iron, leptin, anti-oxidant deficiencies, and intestinal bacteria have all been suggested as potential oxidative stressors. This topic review will focus on the pathogenesis of NAFLD. An approach to such patients is presented separately.

CAUSES OF TRIGLYCERIDE ACCUMULATION
— Hepatic steatosis is a manifestation of excessive triglyceride accumulation in the liver. This can occur from the excessive importation of free fatty acids (FFA) from adipose tissue, from diminished hepatic export of FFA (secondary to reduced synthesis or secretion of VLDL), or from impaired beta-oxidation of FFA (figure 1). The major sources of triglycerides are from fatty acids stored in adipose tissue and fatty acids newly made within the liver through de novo lipogenesis [3]. Excessive importation of FFA can result from either increased delivery of triglycerides to the liver (as seen with obesity and rapid weight loss), or from excessive conversion of carbohydrates and proteins to triglycerides (eg, secondary to overfeeding or use of total parenteral nutrition). Impaired VLDL synthesis and secretion can result from abetalipoproteinemia, protein malnutrition, or choline deficiency. Patients with NASH may have a defect in postprandial Apo B secretion, leading to triglyceride accumulation [4]. In addition a defect in the lipidation of Apo B, caused by an inhibition of microsomal triglyceride transfer protein (MTP), may be a key mechanism in drug-induced NAFLD, such as seen with amiodarone and tetracycline [5]. Depletion of the orphan receptor small heterodimer partner (SHP) results in increased VLDL secretion, elevated MTP levels, and increased insulin sensitivity, whereas induction of SHP results in the rapid accumulation of hepatocyte lipids [6]. Impaired beta-oxidation of FFA to ATP may be seen with vitamin B5 (pantothenic acid) deficiency, excessive alcohol consumption, or coenzyme A deficiency (as can occur with valproic acid or chronicaspirin use). Activation of peroxisome proliferator-activated receptor alpha appears to have a central role in stimulating beta-oxidation and disposing hepatic fatty acids in NASH [7]. The ability to recover from hepatic ATP depletion is severely impaired in patients with obesity-related NASH [8]. Compromised hepatic ATP homeostasis may predispose to injury from other insults. Adiponectin, a fat derived hormone, appears to have a pivotal role in improving fatty acid oxidation and decreasing fatty acid synthesis [9]. Administration of adiponectin improved hepatomegaly, steatosis, and ALT levels in obese, leptin deficient mice. Also implicated in the steatosis pathway is the cannabinoid receptor type 1 (CB1). Administration of a CB1 receptor antagonist rapidly abolished hepatic steatosis, improved aminotransferase levels, reduced the levels of proinflammatory cytokines, and increased adiponectin levels in leptin-deficient mice

SUMMARY AND RECOMMENDATIONS
Nonalcoholic fatty liver disease is a spectrum of disorders that range from simple hepatic steatosis without significant inflammation or fibrosis to nonalcoholic steatohepatitis with varying degrees of inflammation and fibrosis. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement, in most patients with NAFLD, is insulin resistance. Insulin resistance leads to increased lipolysis, triglyceride synthesis, increased hepatic uptake of free fatty fatty acids, and accumulation of hepatic triglyceride. (See 'Insulin resistance' above.) Several fat derived hormones, such as adiponectin, leptin, and resistin, are important regulators of hepatic insulin sensitivity. At the cellular level, these effects appear to be modulated through altered activation of numerous receptors, membrane glycoproteins, and cytokines. Factors that determine the presence and extent of necroinflammation are not yet well understood. Several possible mechanisms have been theorized, including host factors, such as defects in mitochondrial structure and function, impaired freeoxygen radical scavengering, increased hepatic iron, and hepatotoxic byproducts of intestinal bacteria. The factors involved in hepatic fibrogenesis are slowly becoming understood. Activation of both lobular stellate cells and hepatic progenitor cells have been observed in NAFLD. (See 'Fibrosis' above.)

TREATMENT — There is no proven effective therapy for NASH, although modification of risk factors, such as obesity, hyperlipidemia, and poor diabetic control is generally recommended. Weight loss — Weight reduction should be gradual, since rapid weight loss has been associated with worsening of liver disease [65]. One report suggested that weight loss should not exceed approximately 1.6 kg per week in adults [65]. Weight loss and increased physical activity can lead to sustained improvement in liver enzymes, histology, serum insulin levels, and quality of life [66-68]. Improvement in steatosis (but not inflammation and fibrosis) and a decrease in hepatic factors involved in regulating fibrogenesis has been observed one-year following bariatric surgery [26]. In another report, baseline steatosis and insulin resistance were associated with the degree of steatosis one-year after bariatric surgery [27].

SUMMARY AND RECOMMENDATIONS
There is no proven effective therapy for NASH. Attempts should be made to modify potential risk factors such as obesity, hyperlipidemia, and poor diabetic control. Weight reduction should be gradual, since rapid weight loss has been associated with worsening of liver disease. Some hepatologists are already using insulin sensitizing drugs (metformin or pioglitazone) based upon the preliminary data presented above. Further controlled data concerning the efficacy and safety of these approaches should be available in the next few years. Given the slow rate of progression in most patients with NASH, we currently emphasize control of risk factors rather than medical therapy in most patients.

FOLLOW-UP — How patients with NAFLD should be followed is unsettled. Our approach is as follows: For patients with fatty liver without inflammation or fibrosis, we check liver biochemical tests, a complete blood count, platelet count, and prothrombin time annually and request that they be seen by a hepatologist yearly during which a careful search should be performed for physical findings consistent with liver disease. In addition, serial laboratory values should be reviewed to examine for concerning trends, such as a declining platelet count or worsening liver biochemical tests. We repeat a liver biopsy five to six years after the initial biopsy. We do not routinely repeat imaging tests such as an ultrasound. For patients with NASH, we check liver biochemical tests, a complete blood count, platelet count, and prothrombin time every six months and request that they be seen by a hepatologist every six months. We repeat a liver biopsy two to three years after the initial biopsy. We do not routinely repeat imaging tests such as an ultrasound. For patients found to have fatty liver on an imaging test and who either declined to undergo a liver biopsy or in whom a liver biopsy was not immediately indicated (as described above), we check liver biochemical tests, a complete blood count, platelet count, and prothrombin time annually. We also request that they be seen yearly by a hepatologist as described above. We do not routinely repeat imaging tests such as an ultrasound. The above recommendations will change if noninvasive markers of hepatic fibrosis are validated in patients with NAFLD.

Why gastric bypass surgery works
small pouch restricts amount of food eaten 20 ft of small intestine acts as common limb with bile acid (does not cause malabsorption) negative aversion—eg, when candy bar (with1000 osmol/L) eaten, it does not pass through pylorus (candy bar goes directly to small intestine where osmolarity osmol/ L) fluid rushes into small intestine and causes expansion vagal reaction causes patients to feel unwell “they don’t eat candy anymore”

Brain and weight control
brain programmed to eat continuously body weight controlled by, eg, hormonal or vagal messages that shut off eating for about 2 hr within 2 hr, drive to forage for food returns after reaching higher weight, body defends that weight hormones—ghrelin from stomach stimulates appetite peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) turn off hunger

Procedures gastric bypass—causes 37% to 38% weight loss, but weight gradually regained due to lowered metabolism (eg, if 10% of body weight lost, metabolism lowers by 25%) results in 25% weight loss gastric banding—band placed at top of stomach does not alter hormones, so amount of weight loss 50% less than that of other procedures restricts eating slippage—occurs after band placement causes vomiting of fluids one side of band breaks loose from sutures, slips, and rotates around one side and results in obstruction and herniation; surgical emergency gastric pouch—part of stomach removed and stapled Tubularized stomach restricts eating; pylorus intact Lowers ghrelin and increases GLP-1 weight loss results better than with banding (almost as good as gastric bypass)

DM and Gastric Bypass Adjustment of medications for type 2 diabetic with gastric bypass surgery serum glucose likely to drop and normalize normalize due to reduced eating and increased GLP-1 recommend discontinuing agents that reduce serum glucose below normal (eg, glipizide [Glucotrol] and insulin)

Thiamine deficiency Thiamine deficiency: case—6 wk after gastric bypass 50-lb weight loss patient presents with vomiting, vision problems, and symptoms of ataxia often missed Restore thiamine urgently worsens with carbohydrate intake

Pain after gastric bypass
case—1 yr after surgery and 100- lb weight loss, patient presents with epigastric pain of 3-wk duration no nausea or vomiting normal stools ask about use of over-the-counter (OTC) drugs when drug (eg, aspirin) taken, it bypasses stomach, goes directly to small intestine and causes pain

Osteoporosis after gastric bypass
case—woman 52 yr of age presents 7 yr after surgery lost 90 lb, but regained 25 lb menopausal for 4 yr dual energy x-ray absorptiometry (DEXA) shows moderate osteoporosis work-up—check parathyroid hormone (PTH) and 25-hydroxyvitamin D levels chemistry panel hyperparathyroidism secondary to vitamin D deficiency—consider if PTH elevated and vitamin D low patients cannot absorb vitamin D or calcium Replace calcium and vitamin D (start with ergocalciferol, 50,000 U/wk recheck level in 2 wk) give intravenous (IV) bisphosphonates patients cannot acidify calcium bicarbonate (give calcium citrate, mg/day) seen in up to 30% of patients; usually occurs 7 to 10 yr after surgery

Iron deficiency common (60%-90% of patients especially in menstruating women) presents as pica (eg, chewing ice or dirt) since patients in slow metabolic state, inflammatory markers drop (ferritin accurate for measuring iron total ironbinding capacity and serum iron acceptable) due to inability to absorb iron, patients may need IV iron, eg, iron sucrose, 200 mg (reaction [eg, fever, joint aches] rate, 1%-2%)

Vitamin B12 deficiency treat with sublingual form (effective 80% of time) must be taken regularly monitor regularly some patients require monthly vitamin B12 injection

Supplements multivitamin with iron for all patients Calcium citrate
potassium and magnesium early on zinc and copper—enter through same transport system; as zinc replaced, copper malabsorbed necessary to stop one, then start other (“it’s a game, but you have to hang in there with it”) check levels regularly

Conclusions bariatric surgery beneficial (especially to seriously overweight patients with type 2 diabetes) be prepared to withdraw diabetic medications follow nutritional problems check hemoglobin A1C yearly diabetes recurs in some patients as they regain weight 15% of patients who undergo gastric bypass fail (ie, do not lose >20 lb, and regain weight)

Major cause of weight regain
metabolic slowdown Body lowers metabolic rate more than needed weight gain seen in patients who consume 1500 to 1700 calories/day Absorption of medications thyroid replacement therapy— follow thyroid-stimulating hormone levels after gastric bypass every 6 mo to 1 yr 20% to 25% of patients may need increased doses (from, eg, 125 μg/day to μg/day) oral contraceptives (OCs)—after surgery, estrogen levels drop as body fat drops, resulting in heavy menstrual periods maintain patients on standard dosage Celecoxib (Celebrex)—not studied in gastric bypass patients Cannot guarantee use will not result in ulcer

Carotene deficiency common; good general nutritional marker for fat-soluble vitamins check levels 18 mo after surgery can be replaced with OTC Beta-carotene difficult to absorb from fruits and vegetables recommend B complex vitamin Vitamin D monitoring patients require vitamin D supplementation for life PTH levels change after a bout6 wk of vitamin D supplementation check every 6 to 8 wk Thiamine deficiency: rarely seen later than 6 mo after surgery usually occurs within 2 to 3 mo Iron deficiency: cannot be treated with interferon; treat with iron dextrose, iron sucrose, or iron gluconate Criteria for gastric bypass: morbid obesity (2 times normal weight) body mass index (BMI) cutoff, 40 (35 if patient has diabetes or hypertension)

anorexia and bulimia Introduction: 40% of anorexics develop bulimic symptoms patients with BMI <20 to 25 at as high risk for health issues as patients with BMI of 40 to 55 90% of patients with anorexia or bulimia women survey found 7% of white, 7% of Hispanic, and 4% of black students said they took laxatives or vomited to lose weight or to avoid gaining weight normal weight for woman 5'4”—125 lb, BMI 21.5 BMI calculator available online

Constitutional thinness vs anorexia
BMI similar, but percentage of body fat differs leptin related to amount of body fat leptin responds more acutely when body fat reduced due to anorexia, compared to constitutional thinness Anorexic patients amenorrheic (>16% to 17% of body fat required for menstruation) constitutionally thin women menstruate check estradiol levels (should be 30 pg/mL) to verify

General considerations
eating disorders becoming increasingly more common in adults average age of onset for anorexia nervosa (AN) is 15 yr of age bulimia nervosa (BN) 18 yr of age binge eating disorder (BED) 25 yr of age BED more prevalent than AN or BN BED lasts longer, so clinician more likely to see patients with BED than AN or BN embarrassment and difficulty acknowledging problem inhibits initiation of specific eating-disorder therapy Older women—tend to have more comorbidities; longer duration of eating disorder prognosis inversely related to duration of illness BED—falls under Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-1V) classification of eating disorder not otherwise specified (EDNOS) majority of eating disorder patients classified under BED, as patients not meeting criteria for AN or BN included in this diagnosis similar to BN, but without compensatory purging; affects older patients have fewer dietary restraints many patients overweight prevalence— data (10,000 patients) show AN 1.0%; BN 1.5%; BED 3.5% all 3 diagnoses have long duration (average 6 yr for patient with AN)

Common themes intense fear of gaining weight
body image distortion can progress to body dysmorphic disorder Selfperception not based on reality self-esteem totally dependent on weight decreased stigma associated with treatment of mental health conditions and improved access to eating disorder specific therapies likely reasons for increase in older women seeking treatment treatment for BN available since 1990s; epidemiology—incidence of BN and BED increasing since 1960s (era of very thin fashion models [eg, Twiggy] as ideal of female beauty) studies show slow increase in AN throughout last century, although currently at plateau data show patients with eating disorders most likely to seek care from primary care provider; psychiatry and other mental health professionals seen as well as complementary and alternative medicine (CAM) practitioners Onlly 30% of patients with AN seek treatment patients with BN and BED much more likely to do so AN considered egosyntonic illness it does not contradict person’s goals or view of self patients not interested in cure often, patient’s family initiates treatment patient who binges and purges more likely to seek treatment because behaviors cause them distress

Characteristics of older patients
high scores on Beck Depression Inventory significant anxiety measured by State-Trait Anxiety Inventory compromised self-worth elevated scores on all eating disorder assessments; ie, increased dietary restraint eating concerns, weight and shape concerns (compared to normal population) data show 94% of eating disorder patients >30 yr of age have had illness since adolescence or experiencing relapse of preexisting illness de novo illness unusual (6%) older patient more likely to engage in risky behaviors, eg, abuse of over-the-counter (OTC) laxatives and diuretics purchase of prescription diuretics via Internet (can lead to hypokalemia) over-exercise contributing factors— inability to make life transitions or accept losses (eg, death, divorce, empty-nest syndrome, aging, changing appearance) data show majority of older patients struggle with eating issues for 10 yr drive for thinness as strong as in younger patients body image dissatisfaction increases as women age (normative discontent), and more prevalent than in past

Evaluation Scoff questionnaire: mnemonic for sick, control, one, fat and food do you make yourself sick because you feel uncomfortably full? do you worry that you have lost control over your eating? (universally reported in BN and BED) have you lost >14 lb (one stone) in past 3 mo? Do you believe yourself to be fat when others say you are too thin? would you say food dominates your life? 2 positive answers 100% sensitive for AN, BN, and binge eating behavior (not BED) 87.5% specificity Physical examination: temperature (hypothermia common); height, weight and body mass index (BMI); orthostatic blood pressure (BP) and pulse (changes related to increased parasympathetic tone) oropharynx—loss of dental enamel (amalgam islands) and translucent appearance related to vomiting skin and hair—acrocyanosis, lanugo hair, and Russell’s sign (abrasions on knuckles) muscle wasting—BMI <19 (Asians excepted)

Laboratory Values complete blood cell count (CBC) with differential—bone marrow sensitive to malnutrition, so abnormal values seen in white blood cells Hemoglobin platelets (in that order) with eating disorders; Chemistry battery—hypokalemia liver function tests (LFTs)— elevated liver enzymes common (resolve with weight gain); phosphorous and magnesium—levels tend to be low Thyroid function—euthyroid sick syndrome (with abnormal thyroid-stimulating hormone [TSH] levels) common with significant weight loss; repeat TSH testing after weight gain, rather than immediate treatment with thyroid medication pregnancy—urine test electrocardiography—prolonged QT interval dual-energy x-ray absorptiometry (DEXA)—decrease in bone mineral density (BMD) with 6 mo of amenorrhea female athlete triad (amenorrhea, osteoporosis and disordered eating) common among female cross-country runners elevated cholesterol related to cortisol (stress hormone)

Worldwide epidemic of obesity
25% of industrialized world 64% of United States population overweight definitions—overweight defined BMI >25; obesity, BMI >30 (good predictor of development of health risks) Obesity considered lifelong Progressive life-threatening Genetically related multifactorial disease of excess fat storage multiple comorbidities

Physiologic impact of obesity
obstructive sleep apnea Hypoventilation syndrome nonalcoholic fatty liver disease (steatohepatitis leading to cirrhosis) Cholelithiasis Gynecologic abnormalities phlebitis and venous stasis (increases risk for deep venous thrombosis) increased risk for cancer pancreatitis, heart disease direct relationship between weight and diabetes women develop type 2 diabetes with smaller increases in BMI than men obesity and pregnancy spontaneous abortion congenital abnormalities Gestational diabetes Preeclampsia delivery complications postterm onset of labor failed induction shoulder dystocia (increased incidence of third- and fourth-degree tears) neonatal macrosomia (with possible early neonatal death) also precursor for childhood obesity Mortality higher risk for death with increasing weight years of life lost believed greater when weight increases early in life data show bariatric surgery for severe obesity associated with decreased overall mortality

Treatment options estimated only 1% of patients qualifying for bariatric surgery undergo surgery alternatives to surgery diet, exercise, behavior modification antiobesity medications orlistat, sibutramine [Meridia], phentermine challenge is sustaining weight loss data show only 7 of 102 participants maintained weight loss at 9 yr qualifications for surgery BMI >40 BMI >35 with significant comorbidities (diabetes, hypertension, and sleep apnea most important) documented attempts at nonsurgical weight loss why patients choose surgery sustainable weight loss desire to feel healthier improvement in self-esteem increased ability to “keep up” with children Increased fertility bariatric surgery trends number of bariatric procedures projected to continue increasing 80% of bariatric surgery patients women many in childbearing years

Gastric bypass (Roux-en-Y procedure)
restrictive and malabsorptive procedure small stomach pouch stapled and divided from main stomach 2 variations, proximal and distal Malabsorption of fats dumping syndrome—normally, pyloric valve releases food into intestine slowly physiologic reaction to food rapidly leaving stomach small bowel distention, flushing, and Headache remind patients to avoid eating sweets or foods high in fat patients can forget to eat because of changes in ghrelin levels mortality and complication mortality 0.3% Increase with male sex, age, and BMI pulmonary embolism after surgery leak (staple line disconnects or does not heal) 2 most frequent causes of death hemorrhage and stricture technical complications late complications—anastomotic ulcer 5% of patients (may present with epigastric pain) treated with proton pump inhibitor and sucralfate (Carafate) internal hernia in pregnancy serious complication expected outcomes from surgery loss of two-thirds to three-quarters of excess body weight 12 to 18 mo after surgery 60% of weight loss maintained at 14 yr resolution of comorbidities—diabetes in 83% of patients hypertension improved in 87% of patients and eliminated in 75% sleep apnea in 85%

Laparoscopic adjustable gastric band (lap band)
Second most common bariatric surgery performed in United States; restrictive procedure silastic band around stomach connected to subcutaneous port no hormonal changes no dumping syndrome no malabsorption follow-up band adjustments recommended for optimal results if band too tight, patient unable to enjoy healthy foods and likely to resort to eating foods that “slide down” more easily (eg, ice cream, sweets) or may develop reflux disease over time, hunger may increase because ghrelin not as well suppressed as with other types of surgery mortality and complications—mortality approaches zero Obstruction and perforation of stomach unlikely band slip—as patient eats food stomach distends and is pulled underneath band this cuts off blood supply to stomach, leading to necrosis resection required band erosion—erosion seen from inside stomach rare complication port-related problems rate of reoperation (because of complications) higher than gastric bypass; weight loss at 1 yr averages 40%, 52% at 3 yr Longterm weight loss unknown in United States Europe and Australia report loss of 50% excess weight long-term Comorbidities improve not as effective as gastric bypass

Ghrelin Ghrelin is a hormone produced mainly by P/D1 cells lining the fundus of the humanstomach and epsilon cells of the pancreas that stimulates hunger.[1] Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone leptin, produced by adipose tissue, which induces satiation when present at higher levels. In some bariatric procedures, the level of ghrelin is reduced in patients, thus causing satiation before it would normally occur. Ghrelin is also produced in the hypothalamic arcuate nucleus, where it stimulates the secretion of growth hormone from the anterior pituitary gland.[2]. Receptors for ghrelin are expressed by neurons in the arcuate nucleus and the ventromedial hypothalamus. The ghrelin receptor is a G protein-coupled receptor, formerly known as the GHS receptor (growth hormone secretagogue receptor). Ghrelin plays a significant role in neurotrophy, particularly in the hippocampus, and is essential for cognitive adaptation to changing environments and the process oflearning.[3] Recently, ghrelin has been shown to activate the endothelial isoform of nitric oxide synthase in a pathway that depends on various kinases includingAkt.[citation needed]

Ghrelin Mechanism of action
Ghrelin has emerged as the first circulating hunger hormone. Ghrelin and synthetic ghrelin mimetics (the growth hormone secretagogues) increase food intake and increase fat mass[4][5] by an action exerted at the level of the hypothalamus. They activate cells in the arcuate nucleus[6][7] that include the orexigenic neuropeptide Y (NPY) neurons.[8] Ghrelin-responsiveness of these neurones is both leptin- and insulin-sensitive.[9] Ghrelin also activates the mesolimbic cholinergic-dopaminergic reward link, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food, as well as of addictive drugs, such as ethanol.[10][11] [12] [edit]Roles of Ghrelin Lung Development In fetuses, it seems that ghrelin is early produced by the lung and promotes its growth.[13] Learning and Memory Animal models indicate that ghrelin may enter the hippocampus from the bloodstream, enhancing learning and memory.[14] It is suggested that learning may be best during the day and when the stomach is empty, since ghrelin levels are higher at these times. In rodents, X/A-like cells produce ghrelin. Stress-Induced Depression A study appearing in the journal Nature Neuroscience (June 15, 2008 online) suggests that the hormone might help defend against symptoms of stress-induced depression and anxiety.[15] To test whether ghrelin could regulate depressive symptoms brought on bychronic stress, the researchers subjected mice to daily bouts of social stress, using a standard laboratory technique that induces stress by exposing normal mice to very aggressive “bully” mice. Such animals have been shown to be good models for studying depression in humans. The researchers stressed both wild-type mice and altered mice that were unable to respond to ghrelin. They found that, after experiencing stress, both types of mice had significantly elevated levels of ghrelin that persisted at least four weeks after their last defeat encounter. The altered mice, however, displayed significantly greater social avoidance than their wild-type counterparts, indicating an exacerbation of depression-like symptoms. They also ate less than the wild-type mice.[16] Sleep-Duration A study [17] appearing in the journal PLoS Medicine suggests that short sleep duration is associated with high levels of ghrelin and obesity; ghrelin appears to be a factor contributing to the short sleep duration and obesity. Scientists have uncovered an inverse relationship between the hours of sleep and blood plasma concentrations of ghrelin; as the hours of sleep increase, ghrelin concentrations were considerably lower, thereby potentially reducing appetite and avoiding potential obesity.

Ghrelin [edit]Role in Disease
Ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals[18] except in the case of Prader-Willi syndrome-induced obesity. Those suffering from the eating disorder anorexia nervosa have high plasma levels of ghrelin compared to both the constitutionally thin and normal-weight controls.[19] These findings suggest that ghrelin plays a role in both anorexia and obesity. Yildiz and colleagues found that the level of ghrelin increases during the time of day from midnight to dawn in thinner people, suggesting a flaw in the circadian system of obese individuals.[20] Professor Cappuccio of the University of Warwick has recently discovered that shortsleep duration may also lead to obesity, through an increase of appetite via hormonal changes. Lack of sleep produces ghrelin, which stimulates appetite and creates less leptin, which, among its many other effects, suppresses appetite. Ghrelin levels are also high in patients that have cancer-induced cachexia.[21] Prader-Willi syndrome is also characterized by high fasting levels of ghrelin; here the ghrelin levels are associated with high food intake.[22] At least one study found that gastric bypass surgery not only reduces the gut's capacity for food but also dramatically lowers ghrelin levels compared to both lean controls and those that lost weight through dieting alone.[23] [edit]Relation to obestatin Obestatin is a putative hormone that was described, in late 2005, to decrease appetite. Both obestatin and ghrelin are encoded by the same gene; the gene's product breaks apart to yield the two peptide hormones.[24] The purpose of this mechanism is unknown. [edit]History and name The discovery of ghrelin was reported by Masayasu Kojima and colleagues in 1999.[25] The name is based on its role as a growth hormone-releasing peptide, with reference to the Proto-Indo-European root ghre, meaning to grow. The name can also be viewed as an interesting (and incidental) pun, too, as the initial letters of the phrase growth hormone-releasing give us "ghre" with "lin" as a usual suffix for some hormones. [edit]Anti-obesity vaccine Recently, Scripps research scientists have developed an anti-obesity vaccine, which is directed against the hormone ghrelin.[26][27] The vaccine uses the immune system, specifically antibodies, to bind to selected targets, directing the body's own immune response against them. This prevents ghrelin from reaching the central nervous system, thus producing a desired reduction in weight gain.

Sleeve gastrectomy stomach excised leaving only narrow area
Complications include leak or hemorrhage because of long staple line stricture (treated by balloon dilation) Mortality 0.39% (should improve with experience) Stenosis Vitamin B12 deficiency resolution of comorbidities—diabetes 72%; hypertension 57% sleep apnea 85% gaining in popularity

Micronutrients at risk with bypass surgery
iron—lack of stomach acid compromises conversion of ferrous iron to ferric iron intolerance to red meat because of narrow opening leads to less bioavailable heme iron and ascorbic acid prescribed to make up for decreased acid calcium— cells that absorb calcium in jejunum bypassed BMD evaluated with DEXA scan at first and second year after surgery Calcium supplementation prescribed vitamin B12—decreased binding with intrinsic factor replacement can be oral, sublingual, nasal,or intramuscular vitamin D—fat-soluble Requires aggressive replacement to improve calcium absorption Folate and thiamine—deficiencies less common

Pregnancy after weight-loss surgery
data show pregnancy after lap-band surgery as safe as in women with normal BMIs Australian study of 79 patients with lap band showed gestational diabetes rates not significantly different from community less pregnancy-induced hypertension seen relative to pre-lap band pregnancies no significant difference in premature delivery, macrosomia or perinatal mortality, compared to community controls gastrointestinal (GI) complications during antepartum period Cholelithiasis (ursodeoxycholic acid given at time of surgery) Marginal ulcer internal hernia (potentially fatal complication); patient presenting with bowel obstruction who had gastric bypass should be treated as surgical emergency computed tomography (CT) recommended during pregnancy (minimal risk to fetus) to diagnose internal hernia CT insensitive in less severe cases diagnostic laparoscopy should be considered for patients with recurrent symptoms

Nutritional goals determine baseline nutritional status early in pregnancy deficiencies best corrected early or in preconception phase multivitamin plus iron, in addition to prenatal Vitamin recommended (liquid or chewable form because of small opening between stomach and small intestine) Vitamin A >5000 IU/day should be avoided beta carotene can be given at higher dose iron —requirement increases in second half of pregnancy, due to expansion of red blood cell mass and transfer of iron to fetus and placenta Postoperative dose of iron 40 to 100 mg of essential iron per day During pregnancy, 30 to 60 mg per day 180 to 220 mg with maternal anemia (should be given with vitamin C or ascorbic acid) folic acid—400 μg 800 to 1000 μg in typical prenatal vitamin and 400 μg in multivitamin adequate calcium—1200 to 1500 mg with 800 IU of vitamin D

Other pregnancy considerations
oral glucose tolerance test ( g) typically performed at 28 wk gestation Causes dumping syndrome in patients with history of gastric bypass sweating, nausea, flushing, tachycardia, diarrhea, crampy abdominal pain, and hypoglycemia fasting and 2-hr postprandial glucose level, hemoglobin A1C and continuous glucose sensor for 3 days other options pregnant women with history of lap-band surgery should not have electrolyte imbalances or vitamin or iron deficiencies if supplements taken pregnancy should be delayed 12 to 18 mo after weight-loss surgery period of most rapid weight loss Concern baby may become malnourished pregnancy may reduce long-term weight loss (controversial)

Weight gain during pregnancy
gastric bypass requires dietary counseling lap banding requires active management key elements of band management close cooperation with obstetrician fluid removed from band to minimize band restriction determine optimal weight gain for pregnancy recommended lb) fluid added after 14 wk if weight gain excessive fluid removed from band at 36 wk to minimize impact on delivery and establish lactation removal of fluid whenever patient having abdominal surgery

General recommendations
instruct women to use contraception postoperatively fertility issues often resolved after surgical weight loss patient presenting with GI complaints should be assessed for internal hernia multidisciplinary approach to prenatal care of bariatric patients important Determine baseline nutritional status early in course of pregnancy

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