3086 PART 12 Endocrinology and Metabolism

Chronic imbalance of energy intake > Energy expenditure

Expansion of adipose tissue depots

Defective glucose handling

in liver and muscle

Insulin resistance/compensatory hyperinsulinemia

Adipose tissue

Inflammation

Inflammatory

cytokines

Storage of lipid in

nonadipose tissue

Limited fat cell capacity

for continuing storage

FIGURE 401-5 How does obesity cause metabolic disease? Insulin resistance is one of the earliest

complications of obesity and underlies and precedes many of its adverse health consequences. The disposal

and production of glucose by the most important tissues, muscle and liver, respectively, become less sensitive

to insulin, and this results in a compensatory increase in insulin secretion from the pancreas. There are two

main theories for the association of obesity with insulin resistance. In the first, products of macrophages and

other inflammatory cells that are more abundant in obese adipose tissue can, through paracrine or endocrine

routes, disturb insulin’s action in muscle and liver cells. In the second, as adipose storage deposits fill up, they

become less able to take on excessive calories, which end up being stored as ectopic lipid in tissues such as

muscle and liver, which are not primarily designed to store nutrients of this type. The evidence in humans is

stronger for the latter hypothesis.

One hypothesis suggests a leading role for the

inflammation that occurs in the adipose tissue in

obesity (Fig. 401-5). This undoubtedly happens,

as there are more macrophages in obese than

nonobese adipose tissues, and this is associated

with higher levels of inflammatory markers in

the circulation of obese people. The majority of

macrophages in obese adipose tissue are found

in clusters around dead or dying adipocytes,

so it appears that these cells are clearing debris

after cell death. Studies in animal models provide

strong support for the notion that this inflammatory state is mechanistically linked to insulin

resistance, but evidence from humans for this is

not as strong.

An alternative hypothesis is that as individuals

becomes more obese they become less able to

safely store nutrients in their adipose tissue and

begin to redirect macronutrients to other tissues

that are not designed for fat storage and may be

damaged by the nutrient excess. This certainly

happens to people who are born with a lack of

adipose tissue (lipodystrophy) who, early in life,

develop severe versions all the metabolic complications that are seen in obesity as they have

no safe depot in which to store excess nutrients.

There are stronger human data from both genetic

and pharmacologic studies for the existence of

the latter mechanism. How ectopic fat leads to

insulin resistance and other damaging effects is

still a puzzle, but it is very likely a major driver of

pathology associated with obesity.

Metabolic Complications • DYSLIPIDEMIA

The insulin resistance of obesity is frequently associated with dyslipidemia characterized by high circulating triglycerides

and low high-density lipoprotein cholesterol (Chap. 407). Occasionally,

the hypertriglyceridemia may be severe enough to put the patient at

risk of pancreatitis. Although there is a relationship between obesity

and raised circulating levels of low-density lipoprotein cholesterol

(which is the major risk factor for coronary artery disease), genetic

factors independent of obesity and the type of dietary fat consumed

probably have an even greater impact.

FATTY LIVER DISEASE Obesity is strongly associated with the presence of ectopic fat in hepatocytes. This can progress to nonalcoholic

steatohepatitis (NASH), which can progress to the fibrosis, which

is a precursor to cirrhosis (Chap. 343). The reported incidence of

NASH-related cirrhosis and of hepatocellular carcinoma has increased

markedly in step with the increase in the prevalence of obesity in adolescents and adults.

TYPE 2 DIABETES The insulin resistance characteristic of the overnourished state strongly predisposes to the development of type 2

diabetes in people who, largely for genetic reasons, are less able to

maintain the high levels of insulin secretion over many decades.

Impaired glucose tolerance and type 2 diabetes are among the most

common complications of obesity (Chap. 403).

Endocrine Complications In females, the insulin resistance/

hyperinsulinemia frequently found in obesity strongly predisposes

to the development of polycystic ovaries, characterized by irregular

menstruation, anovulatory infertility, and hirsutism due to hyperandrogenism. In males, obesity is more often associated with a degree of

central hypogonadism, where low circulating testosterone is associated

with levels of luteinizing hormone and follicle-stimulating hormone

that do not rise appropriately to compensate for the testosterone-deficient state

Dermatologic Complications Obesity can result in problems

with excessive skin folds that can cause discomfort through mechanical

irritation and can also become infected with fungi. Insulin resistance/

hyperinsulinemia is associated with acanthosis nigricans, where areas

such as axilla, groin, and the back of neck develop velvety hyperpigmentation. Hidradenitis suppurativa is a potentially disabling skin condition strongly associated with obesity. It is characterized by recurrent

boils often with chronically draining sinus tracts affecting skin areas

containing apocrine sweat glands.

Cardiovascular Complications Obese people, even if they do not

have diabetes, have increased morbidity and mortality from atherothrombotic vascular disease, including coronary artery disease and

stroke. The factors that result in this are complex and involve increased

prevalence of hypertension, dyslipidemia, and insulin resistance/

hyperinsulinemia. The rare condition of thrombotic thrombocytopenic

purpura, which causes microvascular platelet thrombosis, thrombocytopenia, and hemolytic anemia due to the presence of abnormally large

von Willebrand factor multimers, is strongly associated with obesity.

Independent of occlusive arterial disease, obese people are also at

increased risk of heart failure, particularly characterized primarily

by diastolic dysfunction, and of atrial fibrillation, the most common

arrhythmia.

Respiratory Complications Exertional dyspnea is common in

obesity, contributed to by the increased work required to move a

greater mass as well as impacts of pressure on the diaphragm and

thoracic cage on chest wall compliance. Enlargement of soft tissue of

the mouth and throat and adipose depots around the airways contribute to the high prevalence of sleep apnea, although other factors may

contribute to some forms, where central nocturnal hypoventilation

also occurs.

Gastrointestinal Disorders Reflux esophagitis is the most common gastrointestinal complication of obesity, particularly occurring

in those with high intraabdominal pressure. Gallstones are also more

common in obese people, bringing increased risks of biliary colic,

cholecystitis, pancreatitis, and gallbladder cancer.

3087Evaluation and Management of Obesity CHAPTER 402

Rheumatologic Disorders Osteoarthritis of the knee and gout

are the two most common rheumatologic conditions clearly associated with obesity. Interestingly, despite obesity being described as a

proinflammatory state, there is no evidence for an increase in rheumatoid arthritis or the seronegative arthritides among people who are

obese.

Cancers Obesity is a risk factor for a number of common cancers.

Indeed, it has recently been calculated that, at least in some countries,

obesity has overtaken smoking as the greatest risk factor for developing

cancer. Recent research has found that as the BMI increases by 5 kg/m2

,

cancer mortality increases by 10%. The largest effects are on colorectal, kidney, and pancreatic cancer, adenocarcinoma of the esophagus,

and, in women, endometrial carcinoma. The recent rapid increase in

the prevalence of esophageal adenocarcinoma is likely related to the

marked recent increase in reflux esophagitis due to the raised intraabdominal pressure (with or without hiatus hernia) characteristic of

central obesity.

Response to Infection The fact that obesity can influence the outcome of some infections has become very apparent with the COVID19 pandemic. Obese patients have a substantially worse outcome if

infected by SARS-CoV-2 through mechanisms that are as yet unclear.

Obese patients also appear to be more susceptible to bacterial wound

infections and postoperative sepsis.

Disorders of the Central Nervous System There is increasing

evidence that obesity is a risk factor for dementia in later life, although

how that risk is mediated is not clear. Idiopathic intracranial hypertension is a rare disorder that is strongly associated with obesity.

■ CONCLUSION

Obesity is a medical disorder that has been greatly increasing in prevalence due to environmental factors that are ubiquitous in developed

and developing countries. However, it is important to bear in mind that

it is a highly heterogeneous condition, which in some people is attributable entirely to genetic causes, and that underlying genetic variation

strongly influences the risk of obesity in all people. It is a serious condition leading to multiple adverse health outcomes and considerable

human suffering. As our understanding of its pathogenesis increases,

our duty to treat obese patients with understanding and compassion

and to develop new and better options for its treatment and prevention

is worthy of emphasis.

■ FURTHER READING

Casazza K et al: Myths, presumptions, and facts about obesity. N Engl

J Med 368:446, 2013.

Farooqi IS, O’Rahilly S: The genetics of obesity in humans. In:

Feingold KR et al (eds). Endotext. South Dartmouth, MA, 2000.

Friedman JM: Leptin and the endocrine control of energy balance. Nat

Metab 1:754, 2019.

Heymsfield SB, Wadden TA: Mechanisms, pathophysiology, and

management of obesity. N Engl J Med 376:1492, 2017.

Leibel RL et al: Changes in energy expenditure resulting from altered

body weight. N Engl J Med 332:621, 1995.

NCD Risk Factor Collaboration (NCD-RISC): Worldwide trends

in body-mass index, underweight, overweight, and obesity from 1975

to 2016: A pooled analysis of 2416 population-based measurement

studies in 128·9 million children, adolescents, and adults. Lancet

390:2627, 2017.

O’Rahilly S: Harveian Oration 2016: Some observations on the causes

and consequences of obesity. Clin Med (Lond) 16:551, 2016.

More than 70% of U.S. adults are considered to be overweight or have

obesity, and the prevalence of obesity is increasing rapidly in most of

the industrialized world. Children and adolescents also are becoming

more obese, indicating that the current trends will accelerate over

time. Obesity is associated with an increased risk of multiple health

problems, including hypertension, type 2 diabetes, dyslipidemia,

obstructive sleep apnea, nonalcoholic fatty liver disease, degenerative

joint disease, and some malignancies. Thus, it is important for health

care providers to identify, evaluate, and treat patients for obesity and

associated comorbid conditions.

■ EVALUATION

Health care providers should screen all adult patients for obesity and

offer intensive counseling and behavioral interventions to promote sustained weight loss. The four main steps in the evaluation of obesity, as

described below, are (1) a focused obesity-related history that includes

lifestyle questions about diet, physical activity, sleep, and stress; (2) a

physical examination to determine the degree and type of obesity; (3)

assessment of comorbid conditions; and (4) assessment of the patient’s

readiness to adopt lifestyle changes.

The Obesity-Focused History The first step in taking an obesity-focused history is to approach the topic in a sensitive manner. The

reason for this concern is that the word obesity is a highly charged,

emotive term. It has a significant pejorative meaning for many patients,

leaving them feeling judged and blamed when labeled as such. This is

not the case when patients are told that they have other chronic diseases such as diabetes or hypertension. Patients prefer that clinicians

use more neutral words or terms such as weight, excess weight, body

mass index (BMI), or unhealthy weight, versus more stigmatizing terms

such as obesity, morbid obesity, or fatness.

Information from the history should address the following seven

questions:

• What factors contribute to the patient’s obesity?

• How is the obesity affecting the patient’s health?

• What is the patient’s level of risk from obesity?

• What does the patient find difficult about managing weight?

• What are the patient’s goals and expectations?

• Is the patient motivated to begin a weight management program?

• What kind of help does the patient need?

Although the vast majority of cases of obesity are promoted by

behavioral factors that affect diet and physical activity patterns, the history may suggest secondary causes that merit further evaluation. Disorders to consider include polycystic ovarian syndrome, hypothyroidism,

Cushing’s syndrome, and hypothalamic disease. Drug-induced weight

gain also should be considered. Common causes include medications for diabetes (insulin, sulfonylureas, thiazolidinediones), steroid

hormones, antipsychotic agents (clozapine, olanzapine, risperidone),

mood stabilizers (lithium), antidepressants (tricyclics, monoamine

oxidase inhibitors, paroxetine, mirtazapine), and antiepileptic drugs

(valproate, gabapentin, carbamazepine). Other medications, such as

nonsteroidal anti-inflammatory drugs and calcium channel blockers,

may cause peripheral edema but do not increase body fat.

The patient’s current diet and physical activity patterns may reveal

factors that contribute to the development of obesity and may identify behaviors to target for treatment. Physical fitness, in particular,

is an important predictor of all-cause mortality rate independent of

BMI and body composition and highlights the importance of taking

a physical activity and exercise history during examination as well as

emphasizing physical activity as a treatment approach.

402 Evaluation and

Management of Obesity

Robert F. Kushner

3088 PART 12 Endocrinology and Metabolism

Inquiring about sleep health that addresses regularity, duration,

efficiency, and satisfaction is also important. Although the mechanisms

are uncertain, sleep deprivation is associated with metabolic alterations

in appetite regulation, sympathetic nervous system overactivity, insulin

sensitivity, and changes in circadian rhythm. Stress may also contribute

to obesity, in part due to activation of the adrenal cortical axis and

elevated cortisol levels and its impact on emotional health and behaviors. This historic information is best obtained by the combination of a

questionnaire and an interview.

BMI and Waist Circumference Three key anthropometric measurements are important in evaluating the degree of obesity: weight,

height, and waist circumference. The BMI, calculated as weight (kg)/

height (m)2

 or as weight (lb)/height (in)2

 × 703, is used to classify

weight status and risk of disease (Table 402-1). BMI is highly correlated

with body fat and is related to disease risk. Lower BMI thresholds for

overweight and obesity have been proposed for the Asia-Pacific region

since this population appears to be at risk for glucose and lipid abnormalities at lower body weights.

Excess abdominal fat, assessed by measurement of waist circumference, is independently associated with a higher risk for metabolic

syndrome, diabetes mellitus, and cardiovascular disease. Measurement

of the waist circumference is a surrogate for visceral adipose tissue

and should be performed in the horizontal plane above the iliac crest

(Table 402-2).

Obesity-Associated Comorbid Conditions The evaluation of

comorbid conditions should be based on presentation of symptoms,

TABLE 402-1 Classification of Weight Status and Disease Risk

CLASSIFICATION

BODY MASS INDEX

(kg/m2

)

OBESITY

CLASS DISEASE RISK

Underweight <18.5 — —

Healthy weight 18.5–24.9 — —

Overweight 25.0–29.9 — Increased

Obesity 30.0–34.9 I High

Obesity 35.0–39.9 II Very high

Extreme obesity ≥40 III Extremely high

Source: Adapted with permission from WHO Consultation on Obesity (1997):

Geneva, Switzerland), World Health Organization. Division of Noncommunicable

Diseases & World Health Organization. Programme of Nutrition, Family and

Reproductive Health (1998). Obesity: preventing and managing the global epidemic:

report of a WHO Consultation on Obesity, Geneva, 3–5 June 1997. World Health

Organization. https://apps.who.int/iris/bitstream/handle/10665/63854/WHO_NUT_

NCD_98.1_%28p159-276%29.pdf?sequence=2&isAllowed=y

TABLE 402-2 Ethnic-Specific Cutpoint Values for Waist Circumference

ETHNIC GROUP WAIST CIRCUMFERENCE

Europeans

Men >94 cm (>37 in)

Women >80 cm (>31.5 in)

South Asians and Chinese

Men >90 cm (>35 in)

Women >80 cm (>31.5 in)

Japanese

Men >85 cm (>33.5 in)

Women >90 cm (>35 in)

Ethnic South and Central

Americans

Use South Asian recommendations until more

specific data are available.

Sub-Saharan Africans Use European data until more specific data

are available.

Eastern Mediterranean

and Middle Eastern (Arab)

populations

Use European data until more specific data

are available.

Source: KG Alberti, P Zimmet, J Shaw; IDF Epidemiology Task Force Consensus

Group. The metabolic syndrome–a new worldwide definition. Lancet 366:1059, 2005.

TABLE 402-3 Obesity-Related Organ Systems Review

Cardiovascular Respiratory

Hypertension Dyspnea

Congestive heart failure Obstructive sleep apnea

Cor pulmonale Hypoventilation syndrome

Varicose veins Pickwickian syndrome

Pulmonary embolism Asthma

Coronary artery disease Gastrointestinal

Endocrine Gastroesophageal reflux disease

Metabolic syndrome Nonalcoholic fatty liver disease

Type 2 diabetes Cholelithiasis

Dyslipidemia Hernias

Polycystic ovarian syndrome Colon cancer

Musculoskeletal Genitourinary

Hyperuricemia and gout Urinary stress incontinence

Immobility Obesity-related glomerulopathy

Osteoarthritis (knees and hips) Hypogonadism (male)

Low back pain Breast and uterine cancer

Carpal tunnel syndrome Pregnancy complications

Psychological Neurologic

Depression/low self-esteem Stroke

Body image disturbance Idiopathic intracranial hypertension

Social stigmatization Meralgia paresthetica

Integument Dementia

Striae distensae

Stasis pigmentation of legs

Lymphedema

Cellulitis

Intertrigo, carbuncles

Acanthosis nigricans

Acrochordons (skin tags)

Hidradenitis suppurativa

risk factors, and index of suspicion. For all patients, a fasting lipid

profile (total, low-density lipoprotein, and high-density lipoprotein

cholesterol and triglyceride levels), chemistry panel, and glycated

hemoglobin should be performed, and blood pressure determined.

Symptoms and diseases that are directly or indirectly related to obesity are listed in Table 402-3. Although individuals vary, the number

and severity of organ-specific comorbid conditions usually rise with

increasing levels of obesity.

Identifying the High-Risk Patient Efforts are under way to

develop more practical and useful assessments to identify patients who

are at high risk in addition to using BMI alone. Analogous to other

staging systems commonly used for congestive heart failure or chronic

kidney disease, the American Association of Clinical Endocrinology

(AACE) and the American College of Endocrinology (ACE) guidelines advocate a simple and clinically useful obesity disease staging

system that is based on ethnic-specific BMI cutoffs in conjunction with

assessment for adiposity-related complications (Fig. 402-1). Stage 0 is

assigned to individuals who are overweight or obese by BMI classification but have no complications, whereas stages 1 and 2 are defined

as individuals who are overweight or obese by BMI classification and

have one or more mild-moderate complications (stage 1) or at least one

severe complication (stage 2). A different functional staging system for

obesity, called the Edmonton Obesity Staging System (EOSS), classifies

individuals with obesity into five graded categories (0–4), based on their

morbidity and health-risk profile along three domains—medical, functional, and mental. In this system, staging occurs independent of BMI.

Assessing the Patient’s Readiness to Change An attempt to

initiate lifestyle changes when the patient is not ready usually leads

3089Evaluation and Management of Obesity CHAPTER 402

• Pre-hypertension

• Hepatic steatosis

• OSA with AHI 5–30

 and mild symptoms

• Osteoarthritis with

 WOMAC score 1–5

• Prediabetes

• Metabolic syndrome

• Type 2 diabetes

• NASH

• Hypertension

• OSA with symptoms or AHI >30

• Osteoarthritis with WOMAC score

 5–10 or knee replacement surgery

• Metabolically healthy

obese

• No biomechanical

 complications

BMI 25–29.9 BMI

Treatment/

prevention

Suggested

therapy

Examples

BMI ≥25 BMI ≥25

BMI ≥30

Secondary Tertiary Tertiary

Prevent complications Treat complications Treat complications

Lifestyle Lifestyle Lifestyle

Consider medication Plus medication

consider surgery

Stage 0

No

complications

Stage 1

Mild-moderate

complications

Stage 2

Severe

complications

FIGURE 402-1 Staging the severity of obesity using the American Association of Clinical Endocrinology clinical practice guidelines. AHI, apnea-hypopnea index; BMI, body

mass index; NASH, nonalcoholic steatohepatitis; OSA, obstructive sleep apnea; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index (a patient-reported

outcome measure for osteoarthritis registering pain, stiffness, and function). (Data from WT Garvey et al: American Association of Clinical Endocrinologists and American

College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract 22 (Suppl 3):1, 2016.)

to frustration and may hamper future weight-loss efforts. Assessment

includes patient motivation and support, stressful life events, psychiatric status, time availability and constraints, and appropriateness of

goals and expectations. Readiness can be viewed as the balance of two

opposing forces: (1) motivation, or the patient’s desire to change; and

(2) resistance, or the patient’s resistance to change.

A helpful method to begin a readiness assessment is to use the motivational interviewing technique of “anchoring” the patient’s interest

and confidence to change on a numerical scale. With this technique,

the patient is asked to rate—on a scale from 0 to 10, with 0 being not so

important (or confident) and 10 being very important (or confident)—

his or her level of interest in and confidence about losing weight at this

time. This exercise helps establish readiness to change and also serves

as a basis for further dialogue.

TREATMENT

Obesity

THE GOAL OF THERAPY

The primary goals of treatment are to improve obesity-related

comorbid conditions and quality of life and reduce the risk of developing future obesity-related complications. Information obtained

from the history, physical examination, and diagnostic tests is

used to determine risk and develop a treatment plan (Fig. 402-2).

The decision of how aggressively to treat the patient and which

modalities to use is determined by the patient’s risk status, expectations, and available resources. Not all patients who are deemed

obese by BMI screening need to be treated, since BMI alone does

not directly measure body fat, distinguish body fat distribution,

or assess an individuals’ health status. However, patients who

present with obesity-related comorbidities and who would benefit from weight-loss intervention should be managed proactively.

Therapy for obesity always begins with lifestyle management and

may include pharmacotherapy or bariatric surgery, depending on

BMI risk category (Table 402-4). Setting an initial weight-loss goal

of 8–10% over 6 months is a realistic target.

LIFESTYLE MANAGEMENT

Obesity care involves attention to three essential elements of lifestyle: dietary habits, physical activity, and behavior modification.

Because obesity is fundamentally a disease of energy imbalance,

all patients must learn how and when energy is consumed (diet),

how and when energy is expended (physical activity), and how to

incorporate this information into their daily lives (behavioral therapy). Lifestyle management has been shown to result in a modest

(typically 3–5 kg) weight loss when compared with no treatment

or usual care.

Diet Therapy The primary focus of diet therapy is to reduce overall

calorie consumption. Guidelines from the American Heart Association/American College of Cardiology/The Obesity Society (AHA/

ACC/TOS) recommend initiating treatment with a calorie deficit of

500–750 kcal/d compared with the patient’s habitual diet. Alternatively, a diet of 1200–1500 kcal/d for women and 1500–1800 kcal/d

for men (adjusted for the individual’s body weight) can be prescribed.

This reduction is consistent with a goal of losing ~1–2 lb/week. The

calorie deficit can be instituted through dietary substitutions or

alternatives. Examples include choosing smaller portion sizes, eating

more fruits and vegetables, consuming more whole-grain cereals,

selecting leaner cuts of meat and skimmed dairy products, reducing

consumption of fried foods and other foods with added fats and

oils, and drinking water instead of sugar-sweetened beverages. It is

important that dietary counseling remains patient centered and that

the selected goals are SMART (specific, measurable, agreed upon,

realistic, timely).

The macronutrient composition of the diet will vary with the

patient’s preference and medical condition. The 2020 U.S. Department of Agriculture Dietary Guidelines for Americans (Chap. 332),

which focus on health promotion and risk reduction, can be applied

to treatment of patients who are overweight or obese. The recommendations include maintaining a diet rich in whole grains,

fruits, vegetables, and dietary fiber; decreasing sodium intake to

<2300 mg/d; consuming fat-free or low-fat dairy products; and

keeping added sugars and saturated fat intake to <10% of daily calories. Application of these guidelines to specific calorie goals can be

3090 PART 12 Endocrinology and Metabolism

Yes

Follow-up and

weight loss

maintenance

Measure weight

and calculate BMI

annually or more

frequently

Advise to

avoid weight gain;

address and treat

other risk factors

Yes

BMI ≥25

Assess and treat risk

factors for CVD and

obesity-related

comorbidities

Assess weight

and lifestyle

histories

Assess need

to lose weight:

BMI ≥30 or BMI 25–29.9

with risk factor(s)

Patient

encounter

Measure weight

height; calculate

BMI

BMI 25–29.9 (overweight)

or 30–34.9 (class I obese)

or 35–39.9 (class II obese)

or ≥40 (class III obese)

No, not yet ready

Evaluation

Treatment

High-intensity

comprehensive

lifestyle

intervention

Alternative

delivery of lifestyle

intervention

Intensive behavioral

treatment; reassess

and address

medical or other

contributory factors;

consider adding or

reevaluating obesity

pharmacotherapy,

and/or refer to

an experienced

bariatric surgeon

Continue intensive

medical management

of CVD risk factors

and obesity-related

conditions; weight

management options

BMI ≥40 or BMI ≥35 with comorbidity.

Offer referral to an experienced

bariatric surgeon for consultation and

evaluation as an adjunct to

comprehensive lifestyle intervention

BMI ≥30 or BMI ≥27 with

comorbidity–option for adding

pharmacotheapy as an adjunct

to comprehensive lifestyle

intervention

Comprehensive

lifestyle intervention

alone or with adjunctive

therapies (BMI ≥30 or

≥27 with comorbidity)

Determine weight loss

and health goals and

intervention strategies

Weight loss

≥5% and sufficient

improvement in health

targets

Assess

readiness

to make lifestyle

changes to achieve

weight loss

Weight loss

≥5% and sufficient

improvement

in health targets

Yes

Yes

Yes, ready

No

No

No, insufficient risk No

BMI 18.5–24.9

FIGURE 402-2 Treatment algorithm—chronic disease management model for primary care of patients with overweight and obesity. This algorithm applies to the assessment

of overweight and obesity and subsequent decisions based on that assessment. BMI indicates body mass index; CVD, cardiovascular disease; FDA, U.S. Food and Drug

Administration. (Reproduced with permission from MD Jensen et al: 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: A report of the

American College of Cardiology/American Heart Association task force on practice guidelines and The Obesity Society. Circulation 129(25 Suppl 2):S102, 2014.)

TABLE 402-4 A Guide to Opting for Treatment for Obesity

BMI CATEGORY (kg/m2

)

TREATMENT 25–26.9 27–29.9 30–34.9 35–39.9 ≥40

Diet, exercise, behavioral therapy With comorbidities With comorbidities + + +

Pharmacotherapy — With comorbidities + + +

Surgery — — — With comorbidities +

Source: Reproduced with permission from U.S. Department of Health and Human Services Public Health Service. National Institute of Health National Heart, Lung and Blood

Institute. The Practical Guide Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NIH Publication Number 00-4084. October 2000.

3091Evaluation and Management of Obesity CHAPTER 402

found on the website www.choosemyplate.gov. Since portion control

is one of the most difficult strategies for patients to manage, the use

of preprepared products such as meal replacements is a simple and

convenient suggestion. Examples include frozen entrees, protein

shakes, and bars. Use of meal replacements in the diet has been

shown to result in a 7–8% weight loss.

Numerous randomized trials comparing diets of different macronutrient composition (e.g., low-carbohydrate, low-fat, Mediterranean) have shown that weight loss depends primarily on reduction

of total caloric intake and adherence to the prescribed diet, not the

specific proportions of carbohydrate, fat, and protein in the diet.

The macronutrient composition will ultimately be determined

by the patient’s taste preferences, cooking style, and culture. However, the patient’s underlying medical problems are also important

in guiding the recommended dietary composition. The dietary

prescription will vary according to the patient’s metabolic profile

and risk factors. A consultation with a registered dietitian for medical nutrition therapy is particularly useful in considering patient

preference and treatment of comorbid diseases.

Another dietary approach to consider is based on the concept of

energy density, which refers to the number of calories (i.e., amount

of energy) a food contains per unit of weight. People tend to ingest

a constant volume of food regardless of caloric or macronutrient

content. Adding water or fiber to a food decreases its energy density

by increasing weight without affecting caloric content. Examples of

foods with low energy density include soups, fruits, vegetables, oatmeal, and lean meats. Dry foods and high-fat foods such as pretzels,

cheese, egg yolks, potato chips, and red meat have a high energy

density. Diets containing low-energy-dense foods have been shown

to control hunger and thus to result in decreased caloric intake and

weight loss.

Occasionally, very-low-calorie diets (VLCDs) are prescribed as a

form of aggressive dietary therapy. The primary purpose of a VLCD

is to promote a rapid and significant (13- to 23-kg) short-term

weight loss over a 3- to 6-month period. The proprietary formulas

designed for this purpose typically supply ≤800 kcal, 50–80 g of

protein, and 100% of the recommended daily intake for vitamins

and minerals. According to a review by the National Task Force on

the Prevention and Treatment of Obesity, indications for initiating

a VLCD include the involvement of well-motivated individuals who

are moderately to severely obese, have failed at more conservative

approaches to weight loss, and have a medical condition that would

be immediately improved with rapid weight loss. These conditions

include poorly controlled type 2 diabetes, hypertriglyceridemia,

obstructive sleep apnea, and symptomatic peripheral edema. In the

DiRECT trial of patients with type 2 diabetes and obesity, a lowenergy formula diet (825–853 kcal/d) was administered for 3 months

following by a structured monthly program. At 12 months, almost

half of the participants achieved remission to a nondiabetic state

and were not taking antidiabetic drugs. Use of formula diets should

be prescribed by trained practitioners in a medical care setting

where medical monitoring and high-intensity lifestyle intervention

can be provided.

Physical Activity Therapy Although exercise alone is only moderately effective for weight loss, the combination of dietary modification and exercise is the most effective behavioral approach for the

treatment of obesity. The most important role of exercise appears to

be in the maintenance of the weight loss. The 2018 Physical Activity

Guidelines for Americans (www.health.gov/paguidelines) recommend that adults should engage in 150 min of moderate-intensity

or 75 min a week of vigorous-intensity aerobic physical activity per

week, preferably spread throughout the week. Focusing on simple

ways to add physical activity into the normal daily routine through

leisure activities, travel, and domestic work should be suggested.

Examples include brisk walking, using the stairs, doing housework

and yard work, and engaging in sports. Additionally, it is important

to reduce sedentary behavior, which is associated with all-cause

mortality and cardiovascular disease mortality in adults. Asking

the patient to wear a pedometer or accelerometer to monitor total

accumulation of steps or kcal expended as part of the activities of

daily living is a useful strategy. Step counts are highly correlated

with activity level. Studies have demonstrated that lifestyle activities

are as effective as structured exercise programs for improving cardiorespiratory fitness and weight loss. A high level of physical activity

(>300 min of moderate-intensity activity per week) is often needed

to lose weight and sustain weight loss. These exercise recommendations are daunting to most patients and need to be implemented

gradually. Consultation with an exercise physiologist or personal

trainer may be helpful.

Behavioral Therapy Cognitive behavioral therapy is used to help

change and reinforce new dietary and physical activity behaviors.

Strategies include self-monitoring techniques (e.g., journaling,

weighing, and measuring food and activity); stress management;

stimulus control (e.g., using smaller plates, not eating in front of

the television or in the car); social support; problem solving; and

cognitive restructuring to help patients develop more positive and

realistic thoughts about themselves. When recommending any

behavioral lifestyle change, the patient should be asked to identify

what, when, where, and how the behavioral change will be performed. The patient should keep a record of the anticipated behavioral change so that progress can be reviewed at the next office visit.

Because these techniques are time consuming to implement, their

supervision is often undertaken by ancillary office staff, such as an

advanced practice provider or registered dietitian.

PHARMACOTHERAPY

Adjuvant pharmacologic treatments should be considered for

patients with a BMI ≥30 kg/m2

 or for patients with a BMI ≥27 kg/m2

who have concomitant obesity-related diseases and for whom

dietary and physical activity therapy has not been successful. When

an antiobesity medication is prescribed, patients should be actively

engaged in a lifestyle program that provides the strategies and skills

needed to use the drug effectively since such support increases total

weight loss.

Medications for obesity fall into two major categories: those that

affect appetite and those that inhibit gastrointestinal fat absorption. Since 2012, four new appetite-controlling medications were

approved by the U.S. Food and Drug Administration (FDA) with

an indication for chronic weight management, although one was

voluntarily withdrawn in February 2020. These medications work

biologically to suppress appetite, affecting hunger, satiety, and

response to highly rewarding foods, thus making it easier for

patients to follow their dietary intentions to restrict caloric intake.

In addition, one capsule that is considered a medical device was

marketed in 2020.

Centrally Acting Medications This class of medications affects

satiety (feeling of fullness after a meal), hunger (the biologic sensation that prompts eating), and craving (intense desire for a specific

food). By controlling appetite, these agents help patients reduce

caloric intake without a sense of deprivation. The target site for

the actions of these medications is primarily the hypothalamus

and reward centers in the central nervous system (Chap. 401).

The classic sympathomimetic adrenergic agents (benzphetamine,

phendimetrazine, diethylpropion, mazindol, and phentermine)

function by stimulating norepinephrine release or by blocking its

reuptake. Among these agents, phentermine is the most commonly

prescribed; there are limited long-term data on its effectiveness.

A 2002 review of six randomized, placebo-controlled trials of

phentermine for weight control found that patients lost 0.6–6.0

additional kg of weight over 2–24 weeks of treatment. The most

common side effects of the amphetamine-derived agents are restlessness, insomnia, dry mouth, constipation, and increased blood

pressure and heart rate.

PHEN/TPM is a combination drug that contains a catecholamine

releaser (phentermine) and an anticonvulsant (topiramate). Topiramate is approved by the FDA as an anticonvulsant for the treatment

3092 PART 12 Endocrinology and Metabolism

of epilepsy and for the prophylaxis of migraine headaches. Weight

loss was identified as an unintended side effect of topiramate

during clinical trials for epilepsy. The mechanism responsible for

weight loss is uncertain but is thought to be mediated through the

drug’s modulation of γ-aminobutyric acid receptors, inhibition of

carbonic anhydrase, and antagonism of glutamate. PHEN/TPM

has undergone two 1-year pivotal randomized, placebo-controlled,

double-blind trials of efficacy and safety: EQUIP and CONQUER.

In a third study, SEQUEL, 78% of CONQUER participants continued to receive their blinded treatment for an additional year. All

participants received diet and exercise counseling. Participant numbers, eligibility, characteristics, and weight-loss outcomes are displayed in Table 402-5. Intention-to-treat 1-year placebo-subtracted

weight loss for PHEN/TPM was 9.3% (15-mg/92-mg dose) and

6.6% (7.5-mg/46-mg dose), respectively, in the EQUIP and CONQUER trials. Clinical and statistical dose-dependent improvements

were seen in selected cardiovascular and metabolic outcome measurements that were related to the weight loss. The most common

adverse events experienced by the drug-randomized group were

paresthesias, dry mouth, constipation, dysgeusia, and insomnia.

Because of an increased risk of congenital fetal oral-cleft formation

from topiramate, women of childbearing age should have a negative

pregnancy test before treatment and monthly thereafter and use

effective contraception consistently during medication therapy.

Lorcaserin was approved by the FDA for chronic weight management in 2012 and taken off the market in 2020. Lorcaserin was

developed as a selective 5-HT2C receptor agonist with a functional

selectivity ~15 times that of 5-HT2A receptors and 100 times that of

5-HT2B receptors. This selectivity is important, since the drug-induced valvulopathy documented with two other serotonergic agents

that were removed from the market—fenfluramine and dexfenfluramine—was due to activation of the 5-HT2B receptors expressed

on cardiac valvular interstitial cells. By activating the 5-HT2C

receptor, lorcaserin is thought to decrease food intake through the

pro-opiomelanocortin (POMC) system of neurons.

Lorcaserin underwent two randomized, placebo-controlled,

double-blind trials for efficacy and safety. Intention-to-treat 1-year

placebo-subtracted weight loss was 3.6% and 3.0%, respectively, in

the two pivotal trials. Modest statistical improvements consistent

with the weight loss were seen in selected cardiovascular and metabolic outcome measurements. However, a postmarketing cardiovascular outcome trial found that more patients taking lorcaserin

(7.7%) were diagnosed with cancer compared to those taking a

placebo (7.1%). The trial was conducted in 12,000 patients over

5 years. A range of cancer types was reported, with several different

types of cancers occurring more frequently in the lorcaserin group,

including pancreatic, colorectal, and lung.

Naltrexone SR/bupropion SR (NB) is a combination of an opioid

antagonist and a mild reuptake inhibitor of dopamine and norepinephrine, respectively. Individually, naltrexone is approved by the

FDA for the treatment of alcohol dependence and for the blockade

of the effects of exogenously administered opioids, whereas bupropion is approved as an antidepressant and smoking cessation aid. As

a combination drug, each component works in consort: bupropion

stimulates secretion of α-melanocyte-stimulating hormone (MSH)

from POMC, whereas naltrexone blocks the feedback inhibitory

effects of opioid receptors activated by the β-endorphin released in

the hypothalamus, thus allowing the inhibitory effects of MSH to

reduce food intake.

The medication has undergone three randomized, placebocontrolled, double-blind trials for efficacy and safety. Participants were

randomized to receive NB (8 mg/90 mg two tablets bid) or placebo

in the three COR studies. Whereas participants received standardized nutritional and exercise counseling in COR-I and COR-II,

a more intensive behavior modification program was provided

in COR-BMOD (Table 402-5). Intention-to-treat 1-year placebosubtracted weight loss was 4.8%, 5.1%, and 4.2%, respectively, in

the COR-I, COR-II, and COR-BMOD trials. Clinical and statistical

dose-dependent improvements were seen in selected cardiovascular and metabolic outcome measurements that were related to

the weight loss. However, the medication led to slight increases or

smaller decreases in blood pressure and pulse than placebo. The

most common adverse events experienced by the drug-randomized

groups were nausea, constipation, headache, vomiting, dizziness,

diarrhea, insomnia, and dry mouth.

Liraglutide, the fourth new medication, is a glucagon-like

peptide-1 (GLP-1) analogue with 97% homology to human GLP-1

that was previously approved for the treatment of type 2 diabetes at

doses up to 1.8 mg once daily. In addition to its effect as an incretin

hormone (glucose-induced insulin secretion), liraglutide inhibits both

gastric emptying and glucagon secretion and stimulates GLP-1 receptors in the arcuate nucleus of the hypothalamus to reduce feeding.

Liraglutide has undergone three randomized, placebocontrolled, double-blind trials for efficacy and safety. Participants

were randomized to receive liraglutide (3.0 mg SC daily) or placebo for initial weight loss—SCALE (patients without diabetes) and

SCALE Diabetes (patients with diabetes)—or for weight maintenance after initial weight loss (SCALE Maintenance) (Table 402-5).

All participants received diet and exercise counseling. For SCALE

and SCALE Maintenance, patients were overweight or obese and

had treated or untreated hypertension or dyslipidemia. Intentionto-treat 1-year placebo-subtracted weight loss was 5.4 and 6.1%,

respectively, in the SCALE and SCALE Maintenance trials. Clinical

and statistical dose-dependent improvements were seen in selected

TABLE 402-5 Clinical Trials for Antiobesity Medications

PHEN/TPM NALTREXONE SR/BUPROPION SR LIRAGLUTIDE

EQUIP CONQUER COR-I COR-II COR-BMOD SCALE

SCALE

MAINTENANCE

No. of participants (ITT-LOCF) 1230 2487 1742 1496 793 3731 422

BMI (kg/m2

) ≥35 27–45 30–45 30–45 30–45 ≥27 ≥27

Age (y) 18–70 18–70 18–65 18–65 18–65 ≥18 ≥18

Comorbid conditions (cardiovascular and

metabolic)

≥1 ≥2 ≥1 ≥1 ≥1 ≥1 ≥1

Mean weight loss (%) with treatment vs

placebo

10.9 vs 1.6 7.8 vs 1.2 6.1 vs 1.3 6.5 vs 1.9 9.3 vs 5.1 8.0 vs 2.6 6.2 vs 0.2

Placebo-subtracted weight loss (%) 9.3 6.6 4.8 4.6 4.2 5.4 6.0

Categorical change in 5% weight loss with

treatment vs placebo

66.7 vs 17.3 62 vs 21 48 vs 16 50.5 vs 17.1 66.4 vs 42.5 63.2 vs 27.1 81.4 vs 48.9

Study completion rate, treatment vs

placebo (%)

66.4 vs 52.9 69 vs 57 50 54 57.9 vs 58.4 71.9 vs 64.4 75 vs 69.5

Note: EQUIP, PHEN/TPM = 15/92 mg dose; CONQUER, PHEN/TPM = 7.5/46 mg dose.

Abbreviations: BMI, body mass index; ITT-LOCF, intention to treat, last observation carried forward; PHEN/TPM, phentermine/topiramate extended release.

3093Evaluation and Management of Obesity CHAPTER 402

cardiovascular and metabolic outcome measurements; however,

there was a small increase in heart rate. The most common adverse

effects include nausea, diarrhea, constipation, and vomiting. GLP-1

agonists should not be prescribed in patients with a family or personal history of medullary thyroid cancer or multiple endocrine

neoplasia.

In approving the new antiobesity medications, the FDA introduced

a new provision with important clinical relevance: a prescription trial

period to assess effectiveness. Response to these medications should

be assessed after 12 weeks of treatment for PHEN/TPM (or 16 weeks

for NB and liraglutide since these medications are uptitrated during

the first month). Determining responsiveness at 3 or 4 months is

based on the post hoc observed trial data that patients who did not

lose a prespecified amount of weight early in treatment were less successful at 1 year. For PHEN/TPM, if the patient has not lost at least 3%

of body weight at 3 months, the clinician can either escalate the dose

and reassess progress at 6 months or discontinue treatment entirely.

For NB, the medication should be discontinued if the patient has not

lost at least 5% of body weight. The corresponding responsive target

for liraglutide is a 4% weight loss.

Peripherally Acting Medications Orlistat is a synthetic hydrogenated derivative of a naturally occurring lipase inhibitor, lipostatin,

that is produced by the mold Streptomyces toxytricini. This drug

is a potent, slowly reversible inhibitor of pancreatic, gastric, and

carboxylester lipases and phospholipase A2

, which are required for

the hydrolysis of dietary fat into fatty acids and monoacylglycerols.

Orlistat acts in the lumen of the stomach and small intestine by

forming a covalent bond with the active site of these lipases. Taken

at a therapeutic dose of 120 mg tid, orlistat blocks the digestion and

absorption of ~30% of dietary fat. After discontinuation of the drug,

fecal fat content usually returns to normal within 48–72 h.

Multiple randomized, double-blind, placebo-controlled studies have shown that, after 1 year, orlistat produces a weight loss

of ~9–10%, whereas placebo recipients have a 4–6% weight loss.

Because orlistat is minimally (<1%) absorbed from the gastrointestinal tract, it has no systemic side effects. The drug’s tolerability

is related to the malabsorption of dietary fat and the subsequent

passage of fat in the feces. Adverse gastrointestinal effects, including

flatus with discharge, fecal urgency, fatty/oily stool, and increased

defecation, are reported in at least 10% of orlistat-treated patients.

These side effects generally are experienced early, diminish as

patients control their dietary fat intake, and only infrequently cause

patients to withdraw from clinical trials. When taken concomitantly, psyllium mucilloid is helpful in controlling orlistat-induced

gastrointestinal side effects. Because serum concentrations of the

fat-soluble vitamins D and E and β-carotene may be reduced by

orlistat treatment, vitamin supplements are recommended to prevent potential deficiencies. Orlistat was approved for over-thecounter use in 2007.

Oral Device Gelesis100 is a nonsystemic, water-soluble gel that

was approved by the FDA in 2019. In the stomach, the capsule

releases the cellulose microgel, which absorbs water and forms

a matrix with the consistency of food, occupying ~25% of the

stomach. In the large intestine, it is broken down by enzymes and

the cellulose is excreted. Gelesis100 and placebo were evaluated

over 24 weeks in patients with BMI of 27 to ≤40 kg/m2

 and fasting

plasma glucose of 90–145 mg/dL. Intention-to-treat, 24-week,

placebo-subtracted weight loss was 2.1% (6.4 vs 4.4%). Gelesis100

treatment had no apparent increased safety risks. The capsules are

approved for patients with a BMI of ≥25 kg/m2

, with or without

comorbidities.

SURGERY

Bariatric surgery (Fig. 402-3) can be considered for patients with

severe obesity (BMI ≥40 kg/m2

) or for those with moderate obesity

(BMI ≥35 kg/m2

) associated with a number of comorbid conditions.

x x

y

y

z

z

100 cm

150 cm

A B

C D E

FIGURE 402-3 Bariatric surgical procedures. Examples of operative interventions used for surgical manipulation of the gastrointestinal tract. A. Laparoscopic adjustable

gastric banding. B. Laparoscopic sleeve gastrectomy. C. The Roux-en-Y gastric bypass. D. Biliopancreatic diversion with duodenal switch. E. Biliopancreatic diversion.

3094 PART 12 Endocrinology and Metabolism

Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. Several distinct types

of DM are caused by a complex interaction of genetics and environmental factors. Depending on the etiology of the DM, factors contributing to hyperglycemia include reduced insulin secretion, decreased

glucose utilization, and increased glucose production. The metabolic

dysregulation associated with DM causes secondary pathophysiologic

changes in multiple organ systems that impose a tremendous burden

on the individual with diabetes and on the health care system. In

the United States, DM is the leading cause of end-stage renal disease

403 Diabetes Mellitus:

Diagnosis, Classification,

and Pathophysiology

Alvin C. Powers, Kevin D. Niswender,

Carmella Evans-Molina

Weight-loss surgeries have traditionally been classified into three

categories on the basis of anatomic changes: restrictive, restrictive

malabsorptive, and malabsorptive. More recently, however, the

clinical benefits of bariatric surgery in achieving weight loss and

alleviating metabolic comorbidities have been attributed largely

to changes in the physiologic responses of gut hormones, bile acid

metabolism, the microbiota, and adipose tissue metabolism. Metabolic effects resulting from bypassing the foregut include altered

responses of ghrelin, GLP-1, peptide YY3-36, and oxyntomodulin.

Additional effects on food intake and body weight control may be

attributed to changes in vagal signaling. The loss of fat mass, particularly visceral fat, is associated with multiple metabolic, adipokine,

and inflammatory changes that include improved insulin sensitivity and glucose disposal; reduced free fatty acid flux; increased

adiponectin levels; and decreased interleukin 6, tumor necrosis

factor α, and high-sensitivity C-reactive protein levels.

Restrictive surgeries limit the amount of food the stomach can

hold and slow the rate of gastric emptying. Laparoscopic adjustable

gastric banding is the prototype of this category. The first banding

device, the LAP-BAND, was approved for use in the United States in

2001. In contrast to previous devices, this band has a diameter that

is adjustable by way of its connection to a reservoir that is implanted

under the skin. Injection of saline into the reservoir and removal

of saline from the reservoir tighten and loosen the band’s internal

diameter, respectively, thus changing the size of the gastric opening.

Although the mean percentage of total body weight lost at 5 years

is estimated at 20–25%, longer-term follow-up has been more disappointing, leading to near abandonment of the procedure. In the

laparoscopic sleeve gastrectomy, the stomach is restricted by stapling

and dividing it vertically, removing ~80% of the greater curvature

and leaving a slim banana-shaped remnant stomach along the lesser

curvature. Weight loss after this procedure is superior to that after

laparoscopic adjustable gastric banding.

The three restrictive-malabsorptive bypass procedures combine

the elements of gastric restriction and selective malabsorption:

Roux-en-Y gastric bypass, biliopancreatic diversion, and biliopancreatic diversion with duodenal switch (Fig. 402-3). Roux-en-Y is

the most commonly undertaken and most accepted bypass procedure. These procedures are routinely performed by laparoscopy.

These procedures generally produce a 30–35% average total

body weight loss at 12–18 months followed by variable weight

regain thereafter. Significant improvement in multiple obesityrelated comorbid conditions, including type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, quality of life,

and long-term cardiovascular events, has been reported. A metaanalysis of controlled clinical trials comparing bariatric surgery

versus no surgery showed that surgery was associated with a

reduced odds ratio (OR) risk of global mortality (OR = 0.55), cardiovascular death (OR = 0.58), and all-cause mortality (OR = 0.70).

Among the observed improvements in comorbidities, the prevention and treatment of type 2 diabetes resulting from bariatric surgery have garnered the most attention. Fifteen-year data

from the Swedish Obese Subjects study demonstrated a marked

reduction (i.e., by 78%) in the incidence of type 2 diabetes development among obese patients who underwent bariatric surgery. Multiple randomized controlled studies have shown greater

weight loss and more improved glycemic control from 1 and

5 years among surgical patients than among patients receiving conventional medical therapy. A retrospective cohort study of >4000

adults with diabetes found that, overall, 68.2% of patients experienced an initial complete remission of type 2 diabetes within

5 years after surgery. However, among these patients, one-third

redeveloped type 2 diabetes within 5 years. Patients with earlierstage type 2 diabetes (i.e., those who do not need insulin, with shorterduration disease, and with lower hemoglobin A1c) appear to have

better improvement after bariatric surgery. The rapid improvement

seen in diabetes after bariatric surgery is thought to be due to caloric

restriction, reduced insulin resistance, and surgery-specific effects on

glucose homeostasis brought about by alteration of gut hormones.

The mortality rate from bariatric surgery is generally <1%

but varies with the procedure, the patient’s age and comorbid

conditions, and the experience of the surgical team. The most

common surgical complications include stomal stenosis or marginal ulcers (occurring in 5–15% of patients) that present as prolonged nausea and vomiting after eating or inability to advance

the diet to solid foods. These complications typically are treated by

endoscopic balloon dilation and acid suppression therapy, respectively. For patients who undergo laparoscopic adjustable gastric

banding, there are no intestinal absorptive abnormalities other

than mechanical reduction in gastric size and outflow. Therefore,

selective deficiencies are uncommon unless eating habits become

unbalanced. In contrast, the restrictive-malabsorptive procedures

carry an increased risk for micronutrient deficiencies of vitamin

B12, iron, folate, calcium, and vitamin D. Patients with restrictivemalabsorptive procedures require lifelong supplementation with

these micronutrients.

Intraluminal Gastric Balloons Three gastric balloon devices are

approved for weight loss that are either placed in the stomach

endoscopically (the REHAPE and ORBERA devices) or swallowed

(OBALON). Efficacy of the devices at 6 months, based on a pooled

weighted-mean percent weight loss, was 9.7%, and the controlsubtracted percent weight loss was 5.6%. The devices are approved

only for up to 6 months of use in adults with a BMI of 30–40 kg/m2