Issues of Concern
Historically, malnourishment was considered the most pressing medical problem in society. Fortunately, social programs, charitable organizations, improved technology, and increased availability of pre-packaged foods in developed societies have made nutrition readily accessible. Notwithstanding, the relative improvement of availability has ushered in a fundamental shift in population health, replacing caloric deficit with caloric excess.[12]
We now see increased body mass index (BMI), expanding waistlines, and an increasing prevalence of comorbid chronic medical conditions led by obesity. Obesity is considered a multifactorial, progressive, and chronic systemic medical problem which can often be complex and relatively difficult to treat.
From a clinical perspective, patients are aware of their need to lose weight and have likely been told by previous healthcare providers to "take charge" of their weight loss. Unfortunately, there have been little-to-no non-surgical strategies to ensure successful and sustainable weight loss until recently. Emerging research has reinforced that the simplest way to ensure successful weight loss over the long term is a graded caloric restriction strategy and physical exercise deployed over several months using monitored compliance. Fundamentally, humans are "creatures of habit." Breaking the reward-feedback loop associated with eating is paramount to controlling dietary habits.[13]
Achieving this control requires understanding the complex behavioral elements of obesity. One must first begin at the molecular level by discussing how food becomes storable energy and how storable energy becomes fat.
Molecular and Physiological Processes Associated With Fat Storage and Energy Utilization
Food consumption must undergo a rigorous and elaborate digestion process to break down into nutrients used for essential bodily functions. At its core, the fundamental building blocks for all cells in our body rely on fats, carbohydrates, and proteins, which we collectively call macronutrients (macros).
Simplistically put, digestion exists in 3-phases: the cephalic phase, the gastric phase, and the intestinal phase. These phases have complex stimulatory/activating and inhibitory hormones that work together to achieve proper food degradation.
In the cephalic phase, sight, smell, and the mere thought of food activate an innate biological reflex. The oral cavity is the location for the mechanical and early enzymatic breakdown of food. The cephalic phase activates salivary glands to produce saliva, which contains lingual lipase and amylase, beginning the process of digestion. This reflex response is triggered by the cerebral cortex acting on the hypothalamus and medulla oblongata, sending signals to the vagus nerve to stimulate gastric juices. This action of pre-signaling will activate and prime the gastrointestinal tract in preparation for the meal. The gastric phase begins upon entry of masticated food into the stomach.
A feedback loop is activated when stretch receptors within the stomach activate a vaso-vagal reflex to trigger the vagus nerve, further stimulating gastric secretory activity. The gastric lumen is an intricate set of epithelial cells with specific secretory activity. These cells protect the stomach lining and assist in secreting enzymes to aid digestion. The intestinal phase arrives when partially digested foods mixed with gastric juices enter the small intestine, where the systemic absorption of macronutrients begins.[14][15][16]
The outlined digestion process breaks down carbohydrates starting in the mouth to their absorbable form (monosaccharides) in the small intestine. Fats become reduced to fatty acid chains and monoglycerides by bile salts secreted from the liver and lipase from the pancreas. Finally, protein is broken down into amino acids by pepsin released from the stomach and various other protein degrading enzymes released from the pancreas.[17]
The fate of monosaccharides, fatty acids, and amino acids depends on the person's energy requirements; if one is in the fed state, the metabolic pathway shifts towards energy storage. Conversely, the metabolic pathway shifts towards oxidizing macronutrients for immediate energy consumption if in the fasting state. Through differing metabolic pathways, monosaccharides, fatty acids, and amino acids can produce acetyl-CoA, which can enter the Kreb cycle and eventually generate energy through oxidative phosphorylation via the electron transport chain in the form of ATP.
Glycogen, primarily stored in the liver, can readily raise serum glucose through glycogenolysis. However, the glycogen storage used is depleted within 12 to 18 hours while in the fasting state. Due to this limitation, the liver possesses the tools to convert non-carbohydrate precursors into glucose, called gluconeogenesis. This process can take place in the liver or cortex of the kidneys and can use precursors such as glycerol (from fatty acids), lactate (from anaerobic metabolism), and glutamine/alanine.[18]
The entire process outlined above works through a delicate balance of hormone regulation. Leptin is a hormone stored in fat cells, and ghrelin is stored in the enteroendocrine cells of the gastrointestinal tract. Leptin suppresses food intake and is considered anorexigenic. Ghrelin stimulates the hunger reflex centrally at the level of the hypothalamus and is deemed to be orexigenic. Ghrelin is believed to be the primary hormone responsible for ushering in the cephalic phase of digestion.
However, existing research has only begun to understand the complex role of these hormones in obesity. For example, subjects with obesity tend to have elevated leptin levels and reduced levels of ghrelin, which is paradoxical to our understanding of the function of these two hormones. However, similar to type 2 diabetes mellitus and insulin, it is postulated that patients with obesity are leptin resistant, but the precise mechanism of obesity induction is yet to be fully elucidated.[19] An intricate understanding of the above molecular and physiological responses is essential to treat this chronic disease properly.
Genetic Factors
The induction of obesity is multifactorial, drawing from genetic, environmental, behavioral, physiological, social, and cultural factors. The possibility of hereditary variables in persons with obesity has been shown by studies comparing adiposity in twins, adoptees, and their parents (biological vs. adoptive) and within families. Studies imply that 40 to 70% of an adult's BMI is inherited.[20][5]
Adolescents with one obese parent have a three- to a fourfold higher chance of becoming obese.[21] The risk of obesity is more than ten times higher if you have two obese biological parents. Unfortunately, even with the extensive composite data of obesity-related gene loci, clinical testing based solely on variations in gene loci currently cannot accurately predict obesity using genes alone.[5]
The single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated (FTO) gene (located on Chr. 16) are found to contribute to the development of diabetes indirectly.[20] In another specific condition, genomic imprinting can produce de novo deletions in paternally derived 15q11-q13, a condition known as Prader-Willi syndrome (PWS). In addition to a characteristic physical appearance, PWS patients suffer from hyperphagia leading to chronic energy intake/expenditure.[22]
Another gene commonly implicated in monogenic childhood obesity is the MC4R, which encodes the melanocortin-4 receptor. The MC4R gene is associated with hyperinsulinemia and increased weight gain in infancy.[23] Leptin, leptin receptor deficiencies, and proopiomelanocortin deficiency are the other genetic causes of obesity. Monogenetic obesity is often severe, manifests at a young age, and is frequently accompanied by other symptoms.
Socioeconomic and Environmental Factors
Epidemiological data has analyzed various geographical factors that may contribute to obesity. Social/cultural factors profoundly influence patients' dietary habits and behaviors. As a result, patients can often have an unhealthy understanding of a proper dietary regimen.
Obesity prevalence is lowest among individuals with the highest income and education, irrespective of race and ethnicity. In urban locations throughout the United States, a diet built entirely on fast-and-prepackaged foods is not uncommon. Much of the discrepancy can be due to the patient's lack of awareness of what foods contribute to chronic obesity.[24][25]
In addition, healthy food options are often cost-prohibitive in urban locations. Due to recent global events, the cost of groceries has sky-rocketed, worsening this disparity in healthy food availability. Low-to-middle income families will turn to cheaper calorie-dense and nutrient-poor options to make ends meet during difficult financial times. In combination with increased stress, socioeconomic factors will play a pivotal role in likely worsening the obesity pandemic across the globe. The worsening of obesity will exacerbate the high rate of chronic, obesity-related conditions, increasing the burden on our already stressed healthcare system.
Advertising that promotes obesity-inducing foods targets specific racial and socioeconomic groups differently. An isolated example of this effect was observed with outdoor food and beverage advertisement density in Sacramento, Los Angeles, New Orleans, Philadelphia, Austin, and New York. Geographical areas with low-income African-American and Latino populations were found to have a higher density of unhealthy food and beverage advertisements in those populations at the most significant risk for developing obesity.[26][27][28][29]
Another factor leading to the higher prevalence of obesity is the high cost of healthy food items. Thus the prevalence of obesity differs across US communities, in contrast to blacks, who had the greatest prevalence (50%) of obesity in the United States, and non-Hispanic Asian adults (17%) had the lowest prevalence.[30] This is probably tied to the social determinants of health, such as access to exercise, a wholesome diet, and general health information.
Obesity hypoventilation syndrome (Pickwickian syndrome) results from diminished ventilatory drive and capacity related to obesity. It is defined as the presence of awake alveolar hypoventilation characterized by daytime hypercapnia (arterial PaCO2 greater than 45mmHg). Its prevalence is largely unknown but based on previous studies and is estimated to be between 20 to 30% of obese patients.[31]
Prenatal and Childhood Factors
Childhood and infancy experiences may predispose to adult obesity. High maternal BMI, high gestational weight gain, gestational diabetes, and maternal type II diabetes may all predispose to adult obesity and metabolic disorders in offspring. By modifying gene expression, maternal obesity may influence the brain regions involved in body weight regulation.[32]
These epigenetic modifications, which may be the consequence of an increase in maternal nutrition supply to the developing fetus, promote increased hunger and fat accumulation in children. Children with obesity are five times more likely to be obese in adulthood.[33] This lends credibility to starting obesity-related prevention strategies earlier to reduce obesity prevalence in adulthood. Another area for improvement is by adding healthier school lunch options. A study using non-linear regression models found that children who attended public schools had a higher BMI regardless of socioeconomic status. Furthermore, those children eligible for free or reduced-cost lunch/breakfast had a higher BMI.[34]
Even though additional data is required to determine the impact of limiting the availability of nutrient-poor/high-sugar goods in schools on obesity, some studies have shown a net-positive result.[35][36][37]
Weight and Adulthood Factors
Between the ages of 20 and 65, most adults acquire weight steadily. Therefore, the probability of becoming overweight (BMI 25 kg/m^2) or obese (BMI 30 kg/m2) during one's lifetime is substantial. The energy imbalance responsible for the rise in obesity over the previous 30 years is estimated to be 100 kcal/day, illustrating that even a small daily positive energy balance may lead to clinically considerable weight gain over time. Weight rises until age 65. After that, the average weight loss is 0.65 kg/year.[38][39]
This is partly owing to a loss in muscle mass (sarcopenia), whereas fat mass increases throughout old age, resulting in a reduced correlation between BMI and fat mass.[40] Aging reduces resting and active energy expenditure and may also affect taste and smell, thus reducing food intake.
Dietary Factors
Over the last seventy years, there has been a major shift in the global food environment, with more people having access to processed, high-calorie foods. US Department of Agriculture (USDA) statistics on dietary energy supply shows that the average daily calorie consumption has risen from 2398 kcal/day/person in the 1970s to 2895 kcal/day/person in the 2000s. This increase in caloric consumption alone can explain the rise in obesity rates seen over this period.
Additionally, the USDA statistics show that Americans consume less fruit, vegetables, and dairy than is advised while consuming more fat, sugar, meats, and grains. The Western Diet is a colloquial term used to describe a diet high in processed foods, such as refined sugars and red meats, which may be excessively salty and sugary. This diet has been adopted primarily in America but has recently begun spreading into parts of Europe and Asia. In general, this diet type is associated with chronic inflammatory states, which are precursors to several chronic diseases such as diabetes, atherosclerosis, and chronic kidney disease.[41]
Eaton et al. described a 'discordance hypothesis' which postulates that the western diet is the primary driver of increasing BMIs due to a mismatch between calories consumed and calories burned.[42]
Hunter-gatherers in our primitive human species would expend a tremendous amount of calories hunting, transporting, and preparing food. However, in our society now, very little energy is expended procuring high-calorie foods, which contributes to our natural tendency to store adipose tissue.
Physical Activity Factors
Physical activity accounts for the greatest variation in total energy expenditure. Reduced regular physical activity and increased sedentary behavior have been linked to an increased risk of obesity.[43] The Amish community, with a low obesity rate, walks 14,000 to 18,000 steps per day, while the average American takes about 5,000 to 6,000 steps per day.[44]
Furthermore, occupational and physical activity has decreased in the United States during the last half-century. Half of the American workforce was fairly active in 1960, but by 2010, over 70 percent were either sedentary or reported little physical activity. This resulted in a decrease in work-related energy expenditure of 140 kcal/day for men and 120 kcal/day for females, which further explains the increasing prevalence of obesity. Adults with physical or mental disabilities are more likely to be obese; those with reduced lower-extremity mobility are at the greatest risk.
Sleep Factors
Epidemiological studies demonstrate substantial and persistent relationships between reduced nocturnal sleep duration, nightshift employment with the development of obesity, and other metabolic disorders.[45][46]
There has been an increase in nightshift employees who spend more time sedentary and less time physically active, resulting in decreased energy expenditure and an increase in the likelihood of obesity. Insufficient sleep also causes the activation of brain regions involved with food reward increasing food consumption, particularly high-fat meals. Thus, adequate sleep and sleep pattern are crucial for lowering adiposity as well as a number of other metabolic ailments.
Medical Factors
Hypothyroidism: Hypothyroidism causes weight gain by reducing basal metabolic rate, thus leading to increased adiposity; however, the weight gain is usually modest and improves with treatment.
Cushing syndrome: The increased levels of glucocorticoids in Cushing disease stimulate 11-beta-hydroxysteroid dehydrogenase type 1 in visceral fat and increase its lipogenic capability leading to adiposity. It is characterized by progressive central adiposity involving the trunk and abdomen, fat accumulation on the face and neck, and muscle wasting in the extremities. Cushing syndrome may result from the excess intake of steroids over a long period (iatrogenic/overdose).
Diabetes is often managed by the use of intensive insulin therapy and home glucose monitoring. Tight control of blood glucose is considered critical in preventing the vascular complications of the condition. However, insulin therapy itself is associated with weight gain.[47][48] It has been suggested that metformin may result in weight loss in patients with type2 diabetes. However, evidence is still lacking to establish this association.[49]
Hypothalamic obesity: Hypothalamic obesity is uncommon and may result from damage (tumor, irradiation, surgery, or elevated intracranial pressure) to the ventromedial or paraventricular area of the hypothalamus or the amygdala, which regulates metabolic information about nutrient storage and food availability. Damage to the ventromedial hypothalamus results in hyperphagia and decreased energy expenditure, leading to obesity. It might be associated with additional symptoms such as headache, nausea, or blurring of vision.[50]
Clinical Significance
Chronic obesity reverberates across many different areas of western society. Since 1970, there has been a nearly doubling incidence of obesity in the United States, reflecting more than two-thirds of Americans now being overweight. In 2008, the estimated cost of obesity was approximately 147 billion dollars annually, representing almost 10% of total healthcare-related spending.[51]
In 2021, that number substantially increased to approximately 260.6 billion dollars.[52] We now know that truncal (abdominal) obesity and increased adipose stores are primary risk factors for developing atherosclerosis, which increases morbidity and mortality from cardiovascular complications. An international classification of obesity exists, with an associated likelihood of morbidity.[53]
Classification of Overweight and Obesity Based on Body Mass Index[53]
|
Class
|
Body Mass Index (kg/m2)
|
Probability of associated comorbidities
|
|
Normal Range
|
18.5–24.99
|
Average
|
|
Preobese
|
25.00-29.99
|
Above-average
|
|
Class I Obesity
|
30.0–34.99
|
Moderate
|
|
Class II Obesity
|
35.0-39.99
|
High
|
|
Class III Obesity
|
>40
|
Very high
|
Truncal obesity contributes to insulin resistance, the primary pathophysiological mechanism for developing type 2 diabetes mellitus. Over a century of research led to discovering a cluster of clinical features, coined in 1988 as metabolic syndrome, or dysmetabolic syndrome X, by Dr. Gerald M. Reaven. These features included elevated blood pressure, blood sugar, serum triglycerides, and low-density lipoprotein.[54]
Although being obese is not necessarily a direct causative factor in developing metabolic syndrome, weight loss can be the most beneficial lifestyle modification a person can make to reduce the risk of complications from metabolic syndrome.[55] The clinical classification of metabolic syndrome is debated, and five-known professional organizations have put out several evidence-based criteria to aid clinicians in arriving at this diagnosis. However, all five organizations have included truncal obesity as a potential risk factor.[56][57]
Patients with obesity have elevated cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta), contributing to metabolic syndrome.[58][7] Chronic obesity is also a risk factor for the development of nonalcoholic fatty liver disease (NAFLD), leading to an increased risk of all-cause mortality.[56][59]
Understanding the multifactorial implications of obesity is paramount to accurately diagnosing and treating the condition. In evaluating a patient who demonstrates features of obesity, the first step is to determine whether the cause is predominately lifestyle or if the result of a secondary condition such as medication use.
One should determine if the patient is taking a medication known to cause obesity. Certain atypical antipsychotics like olanzapine, quetiapine, and risperidone have been shown to cause a net weight gain, with the most substantial weight gain observed with olanzapine. Anticonvulsant and mood stabilizer gabapentin is associated with a 2.2 kg (approximately 5 lb) weight gain within two months.
Also, exercise caution with hypoglycemic agents, particularly in the sulfonylurea class, due to known weight gain associated with tolbutamide (2.8 kg/6 lbs) and glimepiride (2.1 kg/5 lbs). Thiazolidinedione-type hypoglycemic agents have also shown a statistically significant weight gain, particularly pioglitazone (2.6 kg/5.5 lbs).[60]
According to Centers for Disease Control and Prevention (CDC) data, from 2015-2018, approximately 13.2% of adults were on some form of antidepressant medication, with women being the predominant gender receiving prescriptions within this class (17.7%).[61]
However, prescribers should be aware of the antidepressants amitryptiline and mirtazapine, which are associated with a 1.8 kg (4 lbs) and 1.5 kg (3.5 lbs) weight gain, respectively. Glucocorticoids are commonly prescribed in clinical practice for their potent anti-inflammatory effects, which can be useful for treating a broad range of acute and chronic conditions. Unfortunately, glucocorticoids' mechanism of action typically leads to an approximate 4 to 8% rise in weight gain.[62][60]
Enhancing Healthcare Team Outcomes
From a clinical perspective, understanding obesity has gone through a paradigm shift. Previously, clinicians would broadly interpret this disease process as a behavioral issue. The problem with this theory, it creates misplaced blame where the patient may feel inappropriately judged or stigmatized.
Now that we know obesity is a multifactorial disease process, we can build on our knowledge to empower patients to understand obesity through collaboration to explore options for reversing the disease course. It often necessitates a multidisciplinary approach focusing on gradual, sensible lifestyle modifications rather than abrupt weight loss or excessively short-term goals.
Physicians, dietitians, physical therapists, social workers, psychologists, and nurses must collaborate to manage this chronic illness and provide individualized patient care through their unique skills. The doctor is generally a patient's primary source of health information, and their guidance may promote patient motivation.
Routine doctor appointments often fail to address patients' concerns about weight, diet, and physical activity, which might alter the patient's perspective about these conditions. A brief 3-minute lifestyle interview may offer doctors an understanding of patients' eating habits, weight-loss motivation, and mental and physical difficulties.[63]
By stressing diet and obesity-related lifestyle variables, the doctor may urge patients to follow medical advice and consider obesity a serious but manageable health condition. Larger food portions are the main contributor to increased energy intake and obesity; thus, nutritionists may educate patients on the proper portion size, information about the calories and glycemic index in different food items, the unique calorie needs per physical effort, and misconceptions surrounding various fad diets through easy strategies and also to prevent feeling hungry, which may lead to binge eating.
Comprehensive weight reduction counseling must also include methods for both eating less and eating healthier. Patients who consume more low-fat, whole foods (such as fruits, vegetables, legumes, and whole grains) are more likely to consume more nutrients overall. The water content of fresh vegetables is very high, increasing weight and volume to maximize fullness without adding calories.
Diet and exercise together are the most effective obesity treatments. Physical therapists (PT) may urge patients to include non-exercise activity thermogenesis (NEAT), such as standing while using the phone and using stairs instead of elevators, as it can account for a 2,000 kcal difference per day in active vs. inactive adults.[64]
Walking can be a simple exercise, and PT can lead patients toward incremental, manageable objectives, such as adding one minute to a 10-minute walk, ascending one more flight of stairs, or adding 100 steps at a time to a day's total. The physical therapist's role is even more important for patients with musculoskeletal disorders; the therapist may instruct them in exercises that do not need great physical effort and can be as simple as rolling their legs while seated. Knee issues are most prevalent in obese patients; hence, therapists are of the utmost significance to increase physical activity among this patient group.
Numerous mental illnesses may cause weight gain and obesity because eating may be a coping mechanism for depression, despair, stress, and anxiety. Studies have shown that depression, in particular, can lead to unhealthy weight gain due to poor dietary and lifestyle choices, such as choosing to stay inactive out of a lack of motivation or consuming sweet or salty foods to feel good. Psychiatric problems and obesity may form a vicious cycle, with depression/anxiety leading to weight gain and vice versa.
Psychologists may play a crucial role in detecting and treating these underlying issues, and weight reduction can increase confidence and self-esteem substantially. A social worker may aid with allocating resources such as weight loss medications assistance, food stamps, enhancing mobility by supplying walkers and wheelchairs, and locating low-cost gym membership locations such as the YMCA and safe shelters. The nurse is the essential patient contact, may educate patients and follow up weekly in person or by phone to check patient's compliance, making her a crucial element of the multidisciplinary team.
Epidemiologic and Etiologic Considerations of Obesity
