Morbid Obesity

Obesity: The Magnitude of the Problem

Until very recently, obesity was not recognized as a disease, which confounded the ability of physicians to be compensated for treatment they delivered and to treat the condition effectively. The American Medical Association (AMA) officially recognized obesity as a disease in 2013 and in 2014 voted to approve the resolution “that our AMA, advocate for patient access to the full continuum of care of evidence-based obesity treatment modalities (including surgical interventions).”

Morbid obesity is defined as being 100 lbs above ideal body weight, twice ideal body weight, or body mass index (BMI; measured as weight in kilograms divided by height in meters squared) of 40 kg/m ² . The last definition is more accepted internationally and has essentially replaced the former ones for all practical and scientific purposes. A consensus conference by the National Institutes of Health (NIH) in 1991 suggested that the term severe obesity is more appropriate for defining people of such size. This term is used interchangeably with morbid obesity in the remainder of this chapter.

The obesity epidemic in America continues to the point where nearly 40% of the U.S. adult population is obese, and prevalence of obesity in adolescents has increased to 18.5% in the most recent National Health and Nutrition Examination Survey (NHANES). The percentage of obese adults (BMI >30) in the United States increased 16 percentage points from 1980 to 2000, and increased by another 9 percentage points from 2000 to 2016. There are also significant differences in the prevalence of obesity in adults by sex, race, and Hispanic origin. Non-Hispanic Asians (12.7%) had significantly lower rates of obesity than all other race and non-Hispanic origin groups. Non-Hispanic whites (37.9%) had a lower prevalence of obesity than non-Hispanic black (46.8%) and Hispanic adults (47%). Hispanic men (43.1%) had a greater prevalence of obesity compared to non-Hispanic Asian (10.1%) and non-Hispanic black men (36.9%).

Worldwide, from 1975 to 2016, there has been a trend of increasing obesity in children and adolescents (age 5–19) in most regions of the world. The rate of increase in BMI has decreased in most high-income countries since 2000 albeit remaining at a high level. The rate of BMI increase, however, has accelerated in East, South, and Southeast Asia and is expected to surpass moderate to severe underweight children in those areas by 2022. Several countries (Nauru, Cook Islands, Palau, Niue, American Samoa) surpassed the United States in prevalence of obesity, while obesity was more than 20% or more in the United States, Polynesia, Micronesia, Middle East, and North Africa.

The prevalence of morbidly obese adults (BMI >40) has increased to 6.3% of the adult United States population and is the second leading cause of preventable death in the United States. Morbid obesity is second only to smoking on the list of preventable factors responsible for increased health care costs. It is a sobering thought to realize that a 40-year-old morbidly obese man has a 12.4% reduction in life expectancy, or 9.1 years of life lost, compared with a normal-sized man. Moreover, the cost of care is staggering and may be as high as 9% of annual medical expenditures or $147 billion per year. There appears to be significant population heterogeneity between BMI and mortality that is attenuated by increasing age of the individual. Mortality also increases significantly even for individuals with minimal increases in BMI greater than 30.0. Thus, it appears that age, gender, race, and income level all play a role in the development of obesity and obesity-related mortality.

Pathophysiology and Associated Medical Problems

The pathophysiology of severe obesity is multifactorial and has at its basis some genetic predisposition to obesity. There is a clear familial predisposition, and it is rare for a single-family member to have severe obesity. Scientists have identified specific genes that are associated with obesity, including the FTO gene (fat mass and obesity related) that plays a role in controlling feeding behavior and energy expenditure, the MC4R deficiency gene (melanocortin 4 receptor), which is associated with obesity, increased fat mass, and insulin resistance.

Single gene mutations causing obesity are rare, and expressed during early childhood ( Table 48.1 ). The most common single gene etiology of severe obesity is the MC4R, which induces appetite suppression (anorexigenic) effects on the hypothalamus in the regulation of energy homeostasis. Recent studies have suggested that the cilium of MC4R neurons in the hypothalamus is the most common pathway underlying the genetic causes of human obesity ( Table 48.1 ).

Another theory suggests that bacteria within the gut, known as the microbiome, play an essential role in the metabolism and immune system. Simply giving subtherapeutic antibiotic treatment to mice for 4 weeks increases adiposity, plasma levels of insulin, leptin, and triglycerides when the mice are later fed a high-fat diet. The predilection to obesity is transferrable to other mice when the low-dose penicillin-selected gut bacteria are transferred to germ-free hosts, thus identifying that it is the action of the altered gut bacteria, not the antibiotics, that causes the obesity. Recent studies have demonstrated that the gut microbiome circadian rhythm is disrupted by lifestyle differences in developed countries (shift work or jet lag), which provokes the development of altered microbial community, thus predisposing the host to obesity and glucose intolerance. Other studies have shown that degradation of dietary flavonoids through the altered microbiome results in diminished energy expenditure, which leads to obesity. It is fascinating to hypothesize that the current epidemic of obesity relates to changes in the microbiome created by the lifestyle changes and increased use of antibiotics in childhood seen in people who reside in developed countries.

Although there is no definitive answer to the pathophysiology of severe obesity, it is clear that a severely obese individual has, in general, persistent hunger that is not satiated by amounts of food that satisfy the nonobese. This lack of satiety or maintenance of hunger with corresponding increases in calorie intake may be the single most important factor in the process. There appear to be fundamental differences in the satiety and appetite hormonal control of eating that have created the current epidemic. This is hypothesized to occur when the brain’s energy “set-point” rises to increase energy intake, through modulation of the individual’s appetite.

We know that hormones, peptides, and vagal afferents to the brain have a major influence on satiety, appetite, and energy intake. Ghrelin, the only known orexigenic gut hormone, is also known as the hunger hormone and is secreted by P/D1 cells of the gastric fundus. Ghrelin stimulates release of various neuropeptides, such as neuropeptide Y (NPY) and growth hormone, from the hypothalamus, which creates an orexigenic or increased appetite state. Increased levels of ghrelin produce increased food intake, and increased levels of ghrelin develop in individuals after low-calorie diets, thus suggesting that one possible mechanism for the failure of most diets after 6 months is the increase in the appetite hormone ghrelin.

One evolving concept is that the environment causes heritable change in gene function without modification of DNA sequences termed gene-environment interactions . The changes in the epigenome lead to the development of obesity and are much more common than either the monogenetic or the syndromic forms of obesity.

Morbid obesity is a metabolic disease associated with numerous medical problems, some of which are virtually unknown in the absence of obesity. Box 48.1 lists the most common. These problems must be carefully considered when one is contemplating offering a patient weight reduction surgery. The most frequent problem is the combination of arthritis and degenerative joint disease, present in at least 50% of patients seeking surgery for severe obesity. The incidence of sleep apnea is high. Asthma is present in more than 25%, hypertension in more than 30%, diabetes in more than 20%, and gastroesophageal reflux in 20% to 30% of patients. The incidence of these conditions increases with age and the severity and duration of severe obesity.

The metabolic syndrome includes type 2 diabetes mellitus (insulin resistance), dyslipidemia, and hypertension. Patients with this constellation of problems are obese, with central body obesity being the primary essential feature (waist circumference >35 inches in women or >40 inches in men). The syndrome is characterized by impaired hepatic uptake of insulin, systemic hyperinsulinemia, and tissue resistance to insulin. Patients with metabolic syndrome are at high risk for early cardiovascular death.

Obesity has been shown to increase the risk of developing cancer of the thyroid, colon, rectum, esophagus, stomach, kidney, prostate, gallbladder, pancreas, breast (postmenopausal), endometrium, ovaries, and cervix. There are several mechanisms that may be responsible for the increased risk of cancer. Obesity increases chronic inflammation, which is linked to the development of esophageal adenocarcinoma through chronic inflammation from gastroesophageal reflux disease (GERD). Fat produces excess levels of estrogen, which is linked to increased risk of endometrial, ovarian, and postmenopausal breast cancer. Increased levels of insulin and insulin-like growth factor 1 is hypothesized to be linked to the development of colon, prostate, kidney, endometrial, and postmenopausal breast cancer.

Not listed in Box 48.1 are the associated societal discriminatory problems that severely obese individuals face. Public facilities in terms of seating, doorways, and restroom facilities often make access to events held in such settings unavailable to a severely obese person. Travel on public transportation is sometimes difficult, if not impossible. Employment discrimination clearly exists for these individuals. Finally, the combination of low self-esteem, a frequent history of sexual or physical abuse, and these social difficulties coalesce to create a very high incidence of depression in the population of morbidly obese patients.

Medical Versus Surgical Therapy

Medical therapy for severe obesity has limited short-term success and almost nonexistent long-term success. Once severely obese, the likelihood that a person will lose enough weight by dietary means alone and remain at a BMI below 35 kg/m ² is estimated at 3% or less. The NIH consensus conference recognized that for this population of patients, medical therapy has been largely unsuccessful in treating the problem. Review of the clinical trials of lifestyle interventions for prevention of obesity demonstrated that the majority of trials were completely ineffective, and the few that were marginally effective had an extremely small impact on BMI.

One of the most remarkable stories in modern medicine has been the absolute superiority of bariatric surgery over medical therapy for the treatment of morbid obesity and its comorbidities. Multiple long-term follow-up trials comparing morbidly obese diabetics who underwent bariatric surgery with those who did not have shown decreased mortality long term after bariatric surgery as shown in Table 48.2 .

The Swedish Obese Subjects (SOS) study is the first prospective controlled trial to provide long-term data on the effects of bariatric surgery on diabetes, cardiovascular events, cancer, and overall mortality. The study enrolled 2010 bariatric surgery subjects (gastric bypass, 13%; banding, 19%; vertical banded gastroplasty, 68%) and 2037 matched controls who received standard medical treatment and observed the subjects for 10 to 20 years. The SOS study was able to obtain follow-up on 98.9% of the subjects and found at 15 years after initiation that the surgery patients had lost 18% of their body weight, whereas the control group had only a 1% weight loss at 15 years. The long-term sustained weight loss and reduction in comorbid conditions after bariatric surgery resulted in a 29% reduction in mortality in the bariatric surgery patients (adjusted hazard ratio [HR], 0.71; 95% confidence interval, 0.54–0.92; P = 0.01), as shown in Fig. 48.1 . The most common cause of death in the SOS study was cancer (47 in the control group and 29 in the surgery group). The incidence of myocardial infarction was significantly reduced in the surgery group compared with the control group (HR, 0.56), and the surgery group had a lower number of first-time cardiovascular events (HR, 0.67) compared with the control group. Most strikingly, the SOS trial showed an 80% decrease in the annual mortality of diabetic individuals in the surgical weight loss group versus the matched control patients (9% mortality in the surgery group vs. 28% mortality in a control group).

As can be seen in in Table 48.2 , there are multiple studies with long-term follow-up comparing bariatric surgery to matched control groups and found the surgical groups have significant survival advantage (all cause, cancer, cardiovascular), associated with improvement in diabetes, obstructive sleep apnea, dyslipidemia, and hypertension. These studies are convincing evidence that bariatric surgery provides long-term weight loss, resolution of comorbidities, and improvement in mortality. While the SOS study found improvement in all-cause mortality after 10 years of follow-up, the majority of procedures performed were vertical banded gastroplasty but Roux-en-Y gastric bypass (RYGB), a much more effective procedure comprised only 13% of the operations performed. Since RYGB is a more effective procedure, it is not surprising that the Adams and Guidry studies, which compared RYGB to medical treatment, showed convincing mortality differences as early as 3 to 5 years after surgery, much earlier than the Swedish Obesity Study. Similarly, Kauppila studied 49,977 patients undergoing bariatric surgery, of which RYGB made up 73.4% of the operative procedures, and compared to a cohort of obese persons in five Nordic countries and found that all-cause mortality was reduced by 4 years and improved further at 15 years later.

Moreover, in the Adams study, the mortality for the first year was equal in the surgery and control groups (0.53% vs. 0.52%, respectively). The Arterburn study was from the Veterans Affairs (VA) hospitals in the United States, so it had a predominance of males (74% male) as opposed to all of the other reported trials having a majority of female subjects, but it also identified all-cause reduction in mortality at 5 years. The VA study is also remarkable for the higher first year mortality rate in the 2000 to 2005 period (HR, 1.66) than in the 2006 to 2011 period (HR, 0.88), which points to the improvements in surgical care occurring during this period. Despite the higher first year, mortality rate the all-cause mortality rate was lower for the surgery patients than the medical treated group after 5 to 14 years (HR, 0.47).

Adams and colleagues have recently updated the results of the trial reported in 2007 with outcomes measured 12 years after gastric bypass ( N = 418) compared to 417 matched patients who sought but did not undergo surgery and to 321 patients who were matched but never sought to undergo surgery. The improvements in weight and comorbidity were continued at 12 years post-RYGB, as seen in Table 48.3 .

The data from multiple studies comparing medical to surgical treatment strongly supports that bariatric surgery reduces long-term mortality. But does this long-term effect hold true for older patients who have a higher operative mortality and shorter time to see long-term benefits? Surprisingly, a cohort of 7925 morbidly obese patients matched to an equal number of matched control patients not undergoing surgery showed that long-term mortality was lower in the surgery groups for patients age 35 and older. Patients younger than 35 had a significant increase in externally caused deaths (HR = 2.53, P = 0.009), which was even higher in young women (HR = 3.08, P = 0.005). Nevertheless, this study shows that older patients aged 55 to 74 years old had a significant reduction in long-term mortality and the highest reduction of long-term mortality was in men aged 55 to 74 years.

One perception of bariatric surgery is that it may induce profound unalterable changes in eating that negatively affect the patients’ health-related quality of life (HRQOL). A well-done 12-year prospective study evaluated HRQOL changes after gastric bypass surgery compared to two nonsurgical groups matched for similar demographics. The patients who underwent bariatric surgery had greatly improved QOL in the physical component from before surgery. There were also significant differences between the surgery patients and both nonsurgical groups for both the weight-related HRQOL and the physical HRQOL. The magnitude of improvement after 12 years after gastric bypass surgery from before surgery and between matched control groups supports the conclusion that bariatric surgery improves the patient’s quality of life (QOL). However, this study and the SOS study identified an increase in suicides and self-harm in patients undergoing bariatric surgery. The SOS study suicide and nonfatal health self-harm events were greater in the surgery group than in the matched controls ( N = 87 and 49, respectively, out of 68,528 person-years, adjusted HR = 1.78). Analysis of the Utah long-term study revealed that suicide and nonfatal self-harm events were more frequent after gastric bypass than in the intensive lifestyle group ( n = 341 and 84, respectively, out of 149,582 person-years). The authors concluded that bariatric surgery, in particular gastric bypass, was associated with increased risk of suicide or self-harm, but the absolute risk and numbers of patients do not support not offering bariatric surgery to patients. They recommend that preoperative psychiatric mental health assessment and postoperative monitoring for mental health particularly substance abuse is needed.

Metabolic Surgery Versus Medical Therapy for Diabetes

The Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial is 1 of 11 randomized controlled trials (RCTs) that have demonstrated the superiority of bariatric surgery over intensive medical therapy in type 2 diabetes. These trials have shown bariatric surgery to be more effective in glycemic control, weight loss, medication reduction, improvement in lipids, and in QOL, as shown in Fig. 48.2 . Metabolic surgery reduced hemoglobin A1c (HgbA1c) by 2% to 3.5% while medical therapy was only able to reduce HgbA1c by 1% to 1.5%. Short- and long-term (2- to 5- year) results shown in Table 48.4 demonstrate that a significant number of patients (28%–43%) undergoing laparoscopic RYGB (LRYGB) achieved HgbA1c levels less than 6 compared to only 5% to 7% of medically treated patients. It is even more remarkable that the medically treated patients still required intensive medical therapy while the surgery patients had reduced or eliminated diabetic medications. Weight loss for both LRYGB and laparoscopic sleeve gastrectomy (LSG) was far superior to medical therapy. In the case of RYGB, the effect of duodenal bypass on the improvement in diabetes appears to be partially unrelated to weight loss, although in the STAMPEDE trial, the percentage weight loss attained at 1-year postoperative LRYGB was significantly associated with achieving HgbA1c less than 6 at 5 years postoperatively. Thus, whereas there may be a benefit to bypassing the duodenum, the sustained long-term weight loss appears to be an essential element of the salutatory effects of RYGB on type 2 diabetes. LRYGB also improves the other associated medical conditions of the metabolic syndrome, including improvements in hypertension and high-density lipoprotein (HDL) cholesterol, as shown in Table 48.3 , which results in reduced cardiovascular events/deaths. Specifically, diabetic patients who undergo bariatric surgery have a lower rate of incident microvascular disease (16.9% surgery vs. 34.7% medical), with an adjusted odds ratio (AOR) of 0.41. The reduced incidence rate of microvascular disease was largest in the reduction of nephropathy (59% reduction) but also present in diabetic neuropathy (63% reduction) and diabetic retinopathy (45% reduction). The authors of this multi-institution study concluded that bariatric surgery not only improves glycemic control but also significantly reduced the incidence of microvascular disease, which improves survival. The authors argue that this additional evidence of improvement in microvascular disease should push primary care providers to talk to their obese diabetic patients about the benefits of bariatric surgery.

Table 48.4

Randomized prospective trials of bariatric surgery versus medical therapy in treatment of obese type 2 diabetics.

	Schauer LRYGB	Schauer LSG	Ikramuddin Lrygb	Mingrone Lrygb	Simonson Lrygb
HgbA1c
Medical therapy	5% ∗	5% ∗	7%	27% †	0% †
Surgery	29% ∗	23% ∗	38%	42% †	42% †
Change in Weight (Percentage or kg)
Medical therapy	−5%	−5%	−7%	−6.9%	−5.2 kg
Surgery	−23%	−19%	−24%	−28.4%	−24.9 kg

HgbA1c , Hemoglobin A1c; LRYGB , laparoscopic Roux-en-Y gastric bypass; LSG , laparoscopic sleeve gastrectomy.

∗ HgbA1c <6.0%.

† HgbA1c <6.5%.

Bariatric Surgery Mechanism of Action

The first study reporting on the effectiveness of surgery in treating obesity and related comorbid conditions, published by Surgery, Gynecology & Obstetrics, in 1955 reported observing “the amelioration of diabetes mellitus following subtotal gastrectomy.” A few decades later, the wide acceptance of bariatric surgery as treatment for severe obesity has given significant momentum to study the physiology of weight loss surgery. The initial prevailing theory behind bariatric surgery was based on two primary mechanisms for surgically induced weight loss: caloric restriction and nutrient malabsorption. There is little question that the reduction in caloric intake and resulting weight loss are responsible for much of the improvement in comorbidit-comorbidities after bariatric surgery. However, after taking into account the more recent scientific evidence, the concepts of restriction and malabsorption do not fully explain the metabolic effects of bariatric surgery. In fact, the mechanisms seem to extend beyond the magnitude of weight loss alone to include effects on central nervous system regulation of appetite and metabolism and improvements in insulin secretion and insulin sensitivity. Long-term weight loss, improvement in glucose metabolism, and other metabolic effects clearly result from significant postoperative changes in the enteroencephalic and the enteroinsular endocrine axes, as shown in Table 48.5 .

Preoperative Evaluation and Selection