Epidemiology of Obesity and Associated Comorbidities

Abstract

Obesity currently affects 78.6 million people (33%) in the United States and is expected to increase to over 50% of the population by 2030. This epidemic is fueled by the growing rate of obesity in adolescents. The new science of obesity indicates that there is a tipping point at which genetic resetting occurs and it is reached when adipose tissue dysfunction occurs. It is becoming clear that obesity is less an ongoing personal choice than a fact of biology. With this review, we aim to describe the epidemiology of obesity and the associated comorbidities.

Introduction

The biggest myth in healthcare is that obesity is a self-induced problem cured by eating less and getting more exercise. Despite decades of treating obesity with traditional methods of dieting and exercise, progress has not been made. While these conventional methods are successful in people who are overweight, patients with obesity have generally progressed beyond the tipping point, after which traditional ways to lose weight are less effective. The new science of obesity indicates that genetic resetting arises when adipose tissue dysfunction occurs. It is becoming clear that obesity is less an ongoing personal choice than a fact of biology—once a certain level of adiposity dysfunction is established, the person with obesity rarely escapes its consequences.

Obesity currently affects 78.6 million people (33%) in the United States and is expected to increase to over 50% of the population by 2030.¹ This epidemic is fueled by the growing rate of obesity in adolescents.² The healthcare system has the responsibility to provide care to this group of people and accurate tracking of a patient's body mass index (BMI) is critical. As a screening tool, it may identify patients with a BMI of 25 kg/m² and above, who are classified as overweight and are at risk for progression to obesity and related diseases. Identification of this group of people presents a tremendous opportunity to reverse this progression. Current research proves that keeping patients in the overweight range or bringing them to a lower BMI will stave off obesity-related diseases and save billions of dollars in direct and indirect costs.¹ This review aims to describe the epidemiology and the associated comorbidities of obesity.

BMI and Body Adiposity Index

BMI is a measure of weight adjusted for height. BMI is an imperfect tool because it is unable to distinguish overweight due to excess of fat from overweight due to excess of lean mass. Despite its limitations, BMI is currently the most commonly used measure for assessing obesity in adults. The idea of measuring BMI started in the early 1800s. Adolphe Quetelet, a Belgium mathematician, astronomer, and statistician, proposed the Quetelet Index in an article published in 1832 entitled The Average Man and Indices of Obesity. Quetelet recognized the necessity of adjusting weight for differences in body size when comparing levels of obesity in people. This concept was later named the BMI by Ancel Keys. Thanks to these scientists, we now have a formula for measuring it. However, BMI cannot be measured without accurate scales.

Calculations in children and adolescents must be adjusted for age. In addition, BMI may lack correlation with body fat in people with a high proportion of muscle tissue to fat so that athletes with a high BMI still have a low body fat percentage. One alternative method to BMI is the use of the body adiposity index (BAI).³ The BAI correlates directly with body fat percentage and is applicable across populations. However, the BAI has not been widely adopted because of the difficulty with measuring hip circumference and the lack of historical perspective.

Measurements in Asian Americans

Asian Americans, due to the marked difference in body habitus, primarily accumulate weight in their abdominal cavity. Abdominal fat is metabolically very active and causes severe obesity-related diseases—specifically type 2 diabetes. The World Health Organization recommends that overweight in Asian populations should begin at a BMI of 23 and obesity should begin at a BMI of 25. In Japan, a BMI of 25 is defined as obese, and in China, a BMI of 28 is defined as obese. A comprehensive review of the pertinent data for Asian Americans suggests that screening for type 2 diabetes in Asian Americans should actually begin at a BMI of 22.⁴

Measurements in children and adolescents

BMI is used in both adults and children. However, in children, it must be adjusted for age and gender using the CDC's BMI-for-age chart—www.cdc.gov/growthcharts. For example, a 5-year-old boy with a BMI of 20 is likely to be obese, but a 15-year-old boy with a BMI of 20 is likely to be lean. For BMI to be meaningful in children, it must be compared to a reference standard that accounts for the age and gender. National reference standards now exist in the United States and are being developed in other countries.⁵

Epidemiology

Currently, 30% of the world's population is overweight or obese. By 2020, it is estimated that over 60% of the world's population will be overweight or obese. Estimates suggest that the prevalence of severe obesity in 2030 will be 11%, roughly twice the current prevalence.¹ Obesity disproportionately affects minorities, single mothers, and lower socioeconomic groups. In addition, the rate of obesity within the adolescents is escalating.² Obesity occurs on a continuum from overweight to clinically severe obesity. The higher a patient's BMI rises, the higher the risk becomes that the patient will develop obesity-related diseases. Similarly, the severity of the obesity-related diseases increases as BMI rises. Accurate measurement of a patient's BMI is critical as it provides a screening tool to identify patients with a BMI of 25 kg/m² and above, who are classified as overweight and are at risk for progression to obesity and related diseases. Patients in the overweight group (BMI of 25–29.9 kg/m²) have generally not yet experienced amplification of the genetic reset and keeping them in the overweight range or bringing them to a lower BMI will prevent obesity-related diseases.¹

Once a patient gains weight, the environment begins to impact their genes and changes the way the genes work to control weight. As the BMI exceeds 30, their genetic reset generally starts to become apparent as a resistance to weight loss, and as the patient continues to gain weight, they reach a point of no return. Amplification of the genetic reset is a serious condition for the patient, because the genetic reset greatly reduces the patient's ability to reverse or control severe obesity. In fact, once the amplification of the genetic reset has occurred, the patient tends to maintain his weight, despite normal eating patterns and concerted attempts at traditional methods of weight loss. Andreyeva et al. performed a study in which they showed that the group of patients with a BMI of 40 and more has the most rapid growth, and this group has the highest risk for obesity-related diseases.⁶

Child and adolescent obesity

It is estimated that 110 million children and adolescents are now affected by obesity.⁷ The prevalence of obesity in children and adolescents is 17%. Even in early childhood, the incidence of obesity is high. Studies by Cali and Caprio and Cunningham et al. show that for children entering kindergarten, 14.9% are overweight and another 12.4% are obese.^7,8 By eighth grade, 17% are overweight and 20.8% are obese. Overweight 5-year olds are more likely to become obese adolescents. Minority children and children from lower socioeconomic families are disproportionately affected. However, all groups between kindergarten and eighth grade show significant increases in their prevalence of obesity: 65% in Caucasian children, 50% in Hispanic children, 120% in Black children, and 40% among children of other races (Asian, Pacific Islander, Native American, and multiracial). The wealthiest 20% of families have the lowest prevalence of obesity (7.8%) than any other quintiles of socioeconomic status.⁸ Despite these concerning data, many pediatricians are reluctant to measure and share BMI information with parents and the affected children.

The reluctance to measure and share this clinically relevant information as part of the routine examination is a failure as medical providers to help the family understand and address overweight. This reluctance can have devastating long-term effects because we fail to identify, educate, and help children who have not yet been genetically reset to favor obesity. The failure to measure and monitor every child's BMI and to encourage and assist the child and the child's parents in addressing any overweight issues sets the child up for an uninformed and defenseless progression to obesity. The effects of childhood and adolescent obesity are having a negative impact in many ways.

Based on 2013 data, current average life expectancy is 78.8 years in the United States: 76.4 for men and 81.2 for women.⁹ Life expectancy, however, for future generations is expected to decrease due to the prevalence of childhood obesity and related diseases.¹⁰ In addition, the incidence of obesity in adolescents (17%) has a profound impact on their future. Many young people will be disabled by obesity-related diseases at an early age. It is estimated that 10% of children with type 2 diabetes will develop renal failure by early adulthood¹¹ Every study of obesity-related mortality makes clear that children who are obese have the most years of life to lose. In addition, the epigenetics of obesity is becoming clear—parents who are obese pass down inheritable physiology to their children.

Adult obesity

Although the prevalence of obesity appears to be roughly stable in adults, population growth is not. This means the overall number of people with overweight, obesity, and related diseases is increasing dramatically. The population is estimated to grow from 310 million in 2010 to 439 million in 2030 with a prevalence of 42% for obesity. It is projected that by 2050, over 157 million people will be obese and almost as many will be overweight.¹² In addition, the population is becoming increasingly urbanized with the global urban population growing by 65 million a year. Urbanization reduces daily energy expenditure, which in turn increases the risk of becoming overweight and obese.¹³ Over the past 30 years, the population of overweight and obese adults has increased. In 1980, 28.8% of men were overweight and/or obese. By 2013, it was 36.9%. Similarly, in 1980, 29.8% of women in the United States were overweight and/or obese. By 2013, it was 38% of women.

The World Health Organization estimates that, in the year 2010, overweight and obesity caused 3.4 million deaths. Obesity ranks third in the social burdens created by human beings after smoking and armed violence.¹⁴ Obesity rates within minority groups and subpopulations bear similarly alarming information. For example, Blacks, Hispanics, and subpopulations with secondary education or less, all showed an increase in their prevalence of obesity and type 2 diabetes.^15,16

Native Americans

Native Americans are another such subpopulation. Similar to the increase in the general population, the overall number of Native Americans is expected to grow. It is estimated their populations will increase from 235,000 in 2010 to 918,000 in 2050, with a correlating increase in their rates of obesity and type 2 diabetes.¹²

Baby boomers

The United States has experienced dramatic growth in the number of older people during this century. As a result, the aging population presents major implications for national healthcare needs. By 2030, 25% of U.S. residents will be aged 65 or older due to the aging of the baby boomers (i.e., people born between 1946 and 1964).¹² Women represent a significant subgroup within the baby boomer population. In 2003–2004, the obesity rate among women aged 60 years and older was 31.5%. Six years later, in 2010–2012 that rate increased to 38.1%.²

Gender

When it comes to obesity and type 2 diabetes in general, a gender gap appears to exist between men and women. Women are more affected by obesity than men in most countries, but in some countries and population subgroups, this gap is more pronounced. In Egypt, for example, the prevalence of obesity in men is 21% compared to Egyptian women at 45%. In the United States, Black women (57.5%) are far more affected by obesity than Black men (38.1%).¹⁴

Socioeconomic status

The incidence of obesity and type 2 diabetes is affected not only by race but also by socioeconomic status. People in the poor income quartile have higher levels of obesity (26.4%) and extreme obesity (6.8%) compared to those in the high-income quartile (23.6% and 3.3%, respectively).¹⁷ In studies unadjusted for socioeconomic differences in income, Black adults are more affected by obesity than Caucasian adults. However, when the studies are adjusted for socioeconomic differences, the two groups are close to the same—Black and Caucasian adults living in the same socioeconomic status have similar levels of obesity.^18,19 Therefore, racial disparity in obesity rates disappears if socioeconomic conditions are the same.

Associated Comorbidities

Understanding the pathophysiology of obesity-related disease will allow providers to better manage the suite of diseases that affect an individual. Keeping obesity as the central focus and basis of all treatment strategies for obesity-related diseases is essential. This is important for both the management of current diseases as well as the prevention of future diseases.

Insulin resistance and type 2 diabetes mellitus

Insulin resistance (IR) is one of the most significant side effects of obesity. IR has been recognized as the integral feature of metabolic syndrome, which includes glucose intolerance, IR, obesity, hypertriglyceridemia, low high-density lipoproteins, hypertension, and accelerated atherosclerosis. When IR occurs, the pancreas can still produce and secrete insulin, but target cells are unable to respond effectively to blood concentrations. This, in turn, stimulates beta cells in the pancreas to produce higher and higher levels of insulin, making hyperinsulinemia one of the signs of developing IR. IR is primarily seen in the liver, muscle, and adipose tissue. Although many years of study have gone into trying to understand the mechanisms of IR, the etiology is still elusive.

Many studies have established a relationship between clinically observed pathology, but none has established causality. Chronic low-grade inflammation of the adipose tissue is one of the primary mechanisms that occur early in the evolution of IR. Ongoing inflammation is one of the key drivers of metabolic dysfunction leading to IR. Inflammation is detected clinically with elevated blood markers like C-reactive protein. Deletion or silencing of genes that influence insulin action tends to diminish inflammation and improve whole-body glucose metabolism. A reduction in the level of circulating insulin likewise decreases inflammation in adipose tissue.²⁰ Weight gain and weight loss have an influence on chronic inflammation by changing the levels of adiponectin. With weight loss, increasing levels of adiponectin decrease inflammation.²⁰

Type 2 diabetes mellitus (T2DM) is highly related to obesity. For every 1 kg increase in body weight, there is a 4.5% higher risk of developing T2DM.²¹ IR is observed in 90% of patients with T2DM and the presence of IR doubles the risk of cardiovascular diseases.²² Despite strong evidence linking T2DM to higher mortality rates, 40% of patients with T2DM do not meet their treatment goals.²³ The treatment requires weight loss, but it is extremely difficult to achieve even when the patient is committed.

Patients with T2DM who are untreated or sporadically treated for T2DM have a higher than normal energy expenditure. This is due to the increased protein turnover and sympathetic tone. Paradoxically, some patients before diagnosis of T2DM may initially lose weight due to the additional calorie expenditure. Once identification and treatment for T2DM are initiated, the calorie expenditures decrease. Conversely, many of the medications that are prescribed for treatment of T2DM may increase weight. The net result is that patients with T2DM usually gain weight after treatment is begun. However, the most important long-term treatment strategy for T2DM is weight loss. Weight loss trials in obese patients with diabetes show weight loss on average being 4%–10% from baseline. After such weight loss, the patient reaches a new set point, with the lower energy expenditure achieved by therapy. At this point, the patient's internal stimulus to regain weight begins.

The hypothalamic imprinting of the original weight set point begins to exert physiologic pressure on the patient's body to return to the higher original weight by increasing hunger and decreasing satiety. Recurrent attempts at weight loss without substantial results have a frustrating psychological effect and patients often gain additional weight above their initial baseline weight. Physical activity, which has been shown to have significant modulating effects on epigenetic changes that drive IR, is unfortunately rarely emphasized.²⁴ Early identification of IR and treatment can mitigate this paradigm by returning to a normal/moderate BMI long before patients develop diabetes.

Non-alcoholic fatty liver disease

Despite major advancements in fighting certain chronic liver diseases, there is a growing epidemic of liver disease that is directly related to obesity. In the last 20 years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has more than doubled. Fatty liver is now the number one liver disease in the world. Currently, there are no effective drugs. Having a non-alcoholic fatty liver is a strong risk factor for developing T2DM and coronary disease. NAFLD is currently estimated to affect 100 million people in the United States, increasing in incidence with obesity.

Patients with metabolic syndrome are at increased risk for progression to non-alcoholic steatohepatitis: 66% of patients aged 50 years or older who have both diabetes and central obesity show advanced fibrosis on liver biopsies. The mechanism for progression from simple steatosis to NAFLD is not completely understood, but generally involves a multiple hit hypothesis.²⁵ The initial accumulation of fat in the liver progresses into mitochondrial dysfunction and oxidative stress, culminating in liver injury and hepatocyte death. Although many changes are taking place internally, they often go unnoticed by the patient, until cirrhosis is established.

Cardiovascular diseases

Dyslipidemia is a disorder of lipoprotein metabolism in which there are abnormal amounts of lipids in the blood. Dyslipidemia is frequently found in patients with obesity and is often one of the first signals that some metabolic dysfunction is taking place. One in 3 Americans die of heart disease and stroke, and both diseases are related to dyslipidemia.²⁶

Obesity-related hypertension accounts for 65%–75% of hypertension, affecting 1 out of 3 Americans. The mechanisms of hypertension in patients with obesity are not completely understood, but there is strong evidence that it is related to the kidneys. There is evidence that the increase in incidence of chronic kidney disease (CKD) is closely related to obesity. Twenty percent of adults have CKD. In addition, visceral obesity is closely related to hypertension and diabetes, which are the two main contributors of CKD. In patients with hypertension and no history of smoking, alcohol use, chronic obstructive pulmonary disease (COPD), or cardiovascular disease, the lowest mortality occurs with BMI of 23–26.9 kg/m².²⁷ End-stage renal disease increases as BMI increases, with a relative risk of 3.57 for patients with obesity.²⁸ Proposed mechanisms of obesity-related hypertension include the following: hyperleptinemia, angiotensin II activation, hyperinsulinemia, impaired baroreceptor sensitivity, and compression of the kidney by fat accumulation.²⁹

As abdominal fat increases, fat also builds up around the heart. Evidence is accumulating that an increase in visceral fat, producing increased leptin and reduced adiponectin, may be the signal that accelerates the buildup of atherosclerotic plaques and causes plaques to be distributed locally in the coronary arteries.³⁰ A low adiponectin level is also shown to be characteristic of metabolic syndrome.³¹ Diabetes increases the development of cardiomyopathy, leading to a distinct diabetic myocardial phenotype known as diabetic cardiomyopathy (DCM).³² DCM is a progressive disease. Activation of protein kinase C is the early central defect, altering the response of the myocardium to stress. Changes in calcium homeostasis, increase in reactive oxygen species, suppression of aerobic energy production, and modification of contractile proteins are the mechanisms behind the pathophysiology of DCM.³³ Ultimately, IR has also been shown to predict the development of heart failure. Evidence is increasing that IR affects heart muscle and begins a cycle of failure that exacerbates the dysfunctional metabolism, resulting in progression to heart failure. Once heart failure ensues, the increase in sympathetic drive accelerates the heart rate, constricts blood vessels, raises blood pressure, and increases the circulation of free fatty acids and cytokines, thereby worsening heart failure.³⁴

Gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is described as group of symptoms and or mucosal injury that happen as a result of reflux of gastric content into the esophagus. Obesity is a well-established risk factor for developing GERD and its related complications (esophagitis, Barrett's esophagus, etc.). The surgical management of GERD in obese patients is still a matter of debate among surgeons. Nevertheless, as there is substantial association between visceral fat and the pathophysiology of GERD, most would agree that treatment of GERD in obese and nonobese patients can be entirely different. Proper understanding of the pathophysiological mechanisms underlying GERD in obese patients is essential for planning of management and achieving a successful outcome.^35,36

The increased prevalence of obesity has also corresponded with a parallel increased prevalence of GERD.^35,36 Moreover, the link between obesity and GERD is clear on all measures of the disease, including clinical symptoms, erosive esophagitis, acid esophageal exposure, and complications such as Barrett's esophagus and esophageal adenocarcinoma.^36–39 Several epidemiological studies suggest that obese patients have 2–2.5-fold increased risk of heartburn and/or regurgitation.⁴⁰ Various pathophysiologic mechanisms have been proposed that likely lead to the development of GERD. In nonobese patients, the most common cause of GERD is the increased periods of transient lower esophageal sphincter relaxations (TLESR). TLESR have been found to be substantially higher in overweight and obese subjects during the postprandial period, which was accompanied with increased postprandial GERD and esophageal acid exposure. Nevertheless, it has been found that increased intra-abdominal pressure is the main pathophysiological factor that increases the risk of GERD in obese patients. As a result of this increased intra-abdominal pressure, obesity leads to altered gastroesophageal pressure gradients in a way that would promote the retrograde flow of gastric content into the esophagus.³⁸

Pulmonary diseases

The most consistently reported effect of overweight and obesity on lung function is a reduction in functional residual capacity of the lung with preservation of forced expiratory volume and forced vital capacity. In other words, the major effect of obesity is on lung volume. This is worse in visceral obesity and the mechanism is primarily mechanical. In obesity, there is a stiffening of the total respiratory system, which manifests as a rapid, shallow breathing pattern of reduced volumes. Although breathlessness often occurs in patients with obesity, an increase in ventilation can be enough to avoid high CO₂ levels from accumulating.

Obesity and asthma affect the respiratory system through different mechanisms and obesity may increase the severity of asthma. The mechanisms of breathlessness in patients with obesity are still not well understood, but we do know they are not related to lower blood oxygen concentrations.⁴¹ Many investigators are looking closely at the inflammatory pathways generated in obesity as a causal link.⁴² Studies have linked low adiponectin levels and high leptin levels with asthma in both mice and humans, although exact causality in humans has not been firmly established.⁴³

Sleep disorders

There are many inputs to the brain that have not traditionally been considered being connected to weight and metabolic disturbances. Nowadays, many of the pathways that cause physical responses, including key signaling to the brain, are better understood. Disruption of circadian rhythms, sleep disorders, and stress are some of these inputs to the brain that are linked to weight and metabolic processes. Sleep-disordered breathing (SDB) is a term that encompasses various forms of sleep apnea, hypopneas, and respiratory effort-related arousals that occur during sleep. SDB is associated with adverse effects on overall health. SDB affects an estimated 18 million Americans. Obesity is one of the most significant risk factors for the development of SDB. Over 70% of patients with SDB are obese, and 40% of persons with obesity suffer from SDB. Patients with SDB appear to be predisposed to weight gain and have abnormalities in leptin, ghrelin, and other mediators involved in regulating weight gain. The relationship between obesity and SDB may be bidirectional, with SDB actually contributing to obesity and vice versa.⁴⁴

Conclusion

Our global population is increasingly becoming overweight, obese, and suffering from obesity-related diseases. At many levels of healthcare and public policy, obesity remains a disease that is largely unseen, untreated, or ignored. To date, there has been no compelling or strategic plan to manage this problem. In addition, obesity is associated with many metabolic diseases, sometimes grouped as metabolic syndrome, all of which increase the risk for long-term chronic illness and cardiovascular disease. Evidence is accumulating that the pathophysiological changes that occur with obesity may be causative of these diseases (i.e., the presence of IR). The only comprehensive strategy for treatment is through weight loss. In addition, consistent encouragement of the patient to participate in preventive screening is critical. Educating the patient on how to best address the problem can vastly improve their health and quality of life.

Footnotes

Disclosure Statement

No competing financial interests exist.

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