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Obesity

Obesity is currently defined as a body mass index of 30 or greater and affects 1 billion people worldwide.

Overweight and obesity have reached epidemic proportions, now affecting more than 70% of the US adult population and more than  50% of persons worldwide.

The result of a positive energy balance, whereby energy intake exceeds expenditure and results in the storage of energy primarily in lipids in white adipocytes.

The chronic positive energy balance associated with obesity increases triglyceride and adipocyte hypertrophy, followed by hyperplasia from adipogenesis.

The adipose tissue secretes diverse cytokines, proteins, and influences metabolic and physiological function of other organs.

The pathophysiology of obesity is multifactorial with adipocyte expansion leading to underlying an inflammatory state coupled  with lipotoxic insulin signaling, glucotoxicity,  insulin resistance resistance, oxidative stress, and appetite dysregulation

Obesity is associated with chronic low grade inflammation which is important in the development of insulin resistance.

With the progression of obesity pre-adipocyte differentiation becomes dysfunctional with reduced insulin signaling, glucose uptake, and adiponectin release by the mature adipocytes.
Ultimately hypertrophic white adipose tissue growth and expansion restricts the ability of oxygen to diffuse from capillaries into the adipocytes with hypoxia altering the expression of more than 1000 genes and triggering responses that lead to local resistance to both insulin and adrenergic signaling, increased inflammation, and cellular damage.

Energy balance is modulated by food intake and physical care activity, as well as by the dissipation of energy as heat through thermogenesis mitochondria rich adipocytes in brown fat and through inducible thermogenesis in beige adipocytes in white fat.

Adipose based  chronic disease is the greatest noninfectious epidemic of the 21st-century.

More than 40 chronic diseases, including type two diabetes, cancer, and atherosclerosis are associated with obesity.

The medical effects of obesity, especially type two diabetes have a greater impact on some groups- Black, Hispanic, Native Americans than others.

Obesity increases the risk of life-threatening diseases, including type two diabetes, cardiovascular disease, and cancer, and contributes to an estimated 300,000 US deaths per year. 

Obesity could be directly responsible for up to 50% of all new cases of type 2 diabetes.

 

Overweight and obesity are associated with at least 13 types of cancer, including endometrial, breast cancer in postmenopausal women, and colorectal cancer, accounting for up to 40% of all cancers 

diagnosed.

Obesity may contribute to cancer through insulin resistance and abnormalities of insulin growth factor 1 signaling, resulting in increase cell proliferation, chronic low-grade, inflammation, alterations in adipokine physiology, and cellular and vascular perturbations that promote oncogenesis.

Approximately 42% of adults in the US with obesity, have a  body mass index of 30 or greater.

Obesity related costs are estimated at $173 billion annually.

Obesity is accompanied by $1861 excess annual medical expenses per adult in the US, already costing the nation $172.74 billion in medical cost every year.

US obesity rate in 2022 involved at least 35% of adults.

WHO recent estimates that nearly 2,000,000,000 adults and more than 340 million children and adolescents are overweight or obese.

Obesity is associated with multiple types of cancer including: postmenopausal breast, endometrial, ovarian, esophageal adenocarcinoma, gallbladder, gastric cardia, colorectal, renal cell, liver, pancreas, thyroid, meningioma, multiple myeloma- referred to as obesity associated cancers.

 

Obesity is responsible for 41% of uterine cancer‘s, more than 10% of gallbladder, kidney, liver, and colon cancers.

 

Of the 13 cancers linked to obesity, eight have increased in incidence among younger patients, suggesting obesity accelerates development of some cancers and that is why they are showing up in younger people.

 

The link of Cancer by obesity is in part through deoxycholate. 

 

In obese people, the relative proportion of Gram-positive bacteria in gut microbiota is increased resulting in greater conversion of the non-genotoxic primary bile acid, cholic acid, to carcinogenic deoxycholate.

 

Obesity is responsible for 40% of cases of cardiovascular disease in most cases of type two diabetes.

Approximately 90 million US adults, or about 43% live with obesity, and another 25-30% are overweight.

Trends suggest approximately one in two adults will be obese by the year 2030, and severe obesity will become the most common weight class among women and low income individuals.

More than 1.4 billion adults worldwide are overweight and 650 million adults and 124 million children and adolescents have obesity.

Not a single country in the world is less than 20% overweight or obese individuals. 

Many of the poorest nations are facing overweight and obesity levels of 30-50%, or more.

35% or more of American Indian/Alaskan native, Black, and Hispanic adults have obesity.

Obesity is disproportionately present in socioeconomic disadvantage persons and affects 57% of black women.

Obesity is associated with at least $174 billion in annual excess healthcare spending, with the highest excess expenditures occurring once people have reached their 60s; approximately $1500-$3000 per person annually.

Higher coffee consumption is associated with lower total body fat percentage and trunk body fat percentage in a dose-response manner among women. 

The economic impact of illness related to excess body weight was estimated at $2 trillion globally in 2014.

Some of the largest increases in obesity in low and middle income countries likely is the result of the introduction of the western lifestyle, consisting of energy-dense, nutrient poor food, along with reduce physical activity levels.

Obesity rates among individuals who have not completed high school are almost double than those among college graduates and offspring of college graduates.

Obesity rates are higher among peoplencovered by Medicaid then among people with commercial insurance.

Obesity is influenced by genetic expression, energy homeostasis is determined by feedback between circulating neuropeptide hormones, and the CNS.

The gut – brain axis responds to G.I. tract, adipose tissue and circulating hormone signals to stimulate or inhibit central neurons of society, or hunger.

Dysregulation of the system occurs in obesity, leading to greater hunger and decreased satiety.

Hormones involved  in this process are leptin, ghrelin, peptide yy, gastric inhibitory polypeptide, glucagon like peptide1,  pancreatic polypeptide, amylin, and cholectstokinin increase  weight by influencing appetite, satiety, and food palatability.

Thermogenesis is triggered by mechanisms within cells or by the sympathetic nervous system in response to exercise, diet, or exposure to cold.

Regulation of mitochondrial thermogenesis include IRG1, PGC1alpha, PRDM16 and TBX15 which control expression of gene encoding uncoupling protein1 (UCP1), which the polarizes the inner mitochondrial membrane causing proton transfer and heat dissipation.

Identical twin studies have shown that differing body mass index is due to different mitochondrial RNA signatures in fat cells, indicating a link between mitochondrial dysfunction and adiposity.

Genes and environment interact to regulate the energy  balance, and weight status, making obesity a chronic disease requiring long-term management.

Adverse workplace, school, social, and home environment can be obesogenic.

The greater availability of fast food, restaurants, poor neighborhood, walk, ability, and perceive safety risks can limit physical activity and healthy food options.

Adult misperception of their weight is common: self-reported height and weight assays reveals that more than half of participants report themselves as normal weight when in fact they are overweight, and 47% reported themselves as overweight when they were obese based on BMI (Rosenthal RJ).

Patients with individuals with a BMI greater than 55 kg/m² have a 14 year reduced life expectancy.

Life expectancy is reduced by obesity by 5-20 years.

It affects approximately 107.7 million children and adolescents worldwide and is associated with multiple conditions and complications.

More than 70% of persons who have obesity before puberty will have obesity as adults.

Most people are genetically susceptible with availability of highly processed foods, calorie dense foods, decreased physical activity, disrupted meal patterns, inadequate sleep, increased stress, social isolation, disturbed circadian rhythms, and exposure to medications that promote weight gain.

Many medications promote weight gain, and include: anti-hyperglycemia agents, anti-depressants, antipsychotics, antiepileptics, beta blockers, progesterone based contraceptives, corticosteroids, and anti-retroviral therapies.

Many weight gain promoting medications increase the risk of weight related complications, including cardiovascular disease, diabetes, and hepatic steatosis.

Genetic variants are implicated in its development with most forms of obesity  having polygenic risk factors with several variants strongly associated.

Obesity due to a single gene variant is rare.

The obesity propensity across the lifespan is strongly influenced by the environment and social context in which a child is born, grows, and ages.

Minority children born and raised in racially segregated communities characterized by high density of fast food outlets, limited access to fresh fruits and vegetables, and poor walkability are more likely develop obesity and hypertension.

Drugs used to treat psychiatric disorders, type two diabetes, hypertension, osteoarthritis are associated with weight gain.

Among adults misperception of weight status, that is the discrepancy between actual measured week and perceive wait status is common and is a burden for efforts to reduce weight.

In obese patients with a BMI characteristic of being overweight (25-29.9 Kilograms per meter squared) 59% of patients consider themselves to be a normal weight, while participants whose BMI met the criterion of obesity, that is, a BMI of 30 kg/mg² classify themselves as being in the overweight range instead.

At least 2.8 million adults die each year as a result of being overweight or obese.

In addition, 44% of the diabetes burden, 23% of the ischemic heart disease burden and between 7% and 41% of certain cancer burdens are attributable to overweight and obesity.

Nearly 3/4 of adults older than 20 years in the US meet criteria for being obese, and 42% are obese by BMI.

Appoximately 7% of deaths worldwide are attributed to overweight or obesity.

Obesity has stigmata and prejudice associated with it, particularly toward heavier individuals.

Weight stigmata is common and leads to poor healthcare, less screening, preventive counseling, and emotional support.

Physiologic changes associated with obesity can affect drug absorption, distribution, metabolism and excretion.

Normoglycemic obese patients have a high prevalence of neuropathy, indicating that obesity alone is sufficient to cause neuropathy. 

The prevalence of neuropathy is about 20% in obese individuals.

Physiologically, obesity creates a inflammatory state, which is a chronic low-grade systemic or innate immune activator, and in part mediates increased pro inflammatory cytokines: inflammaging.

This inflammatory state can suppress adaptive immune responses can result in a heightened susceptibility to infection, poor vaccine responses, and increased inflammatory related pathology.

The intestinal microbiome has a role in the pathophysiology of obesity by influencing the host energy metabolism, adiposity, neuroendocrine signaling, and insulin sensitivity.

Weight gain causes expansion of fat in ectopic sites, such as the heart, liver, kidney, muscle, blood vessels, and viscera, which contributes to manifestations of cardiometabolic disease.

Recognized as a leading contributed to morbidity and mortality.

Up to 18% of patients with obesity undergoing surgery have postop pulmonary complications, which is almost 2 times the risk of normal weight or overweight patients.

With obesity the work of breathing is increased as adipose tissue restricts the normal movement of the chest muscles,  makes the chest wall less compliant, the diaphragm moves less effectively, respiratory muscles are fatigued more easily, and airflow in and out of the lung is impaired by excessive tissue in the head and neck area. 

People with obesity need to expend more energy to breathe effectively.

The economic impact of illness related to excess bodyweight is estimated at $2 trillion globally in 2014 (NCD Risk Factor Collaboration).

The gut microbiome has a roll in the pathophysiology of obesity by influencing host energy metabolism, adiposity, neuroendocrine signaling, and insulin sensitivity.

The gut microbiome may be responsible in part for individual differences in outcomes of obesity directed interventions.

Often begins in childhood, with the highest rates among minority populations.

Growth restricted newborns have a lifelong propensity for obesity.

Patients with adverse childhood experiences including emotional and sexual abuse have almost the double risk of severe obesity.

Sexual abuse is common among patients with obesity.

Infancy is a critical period of development with long lasting metabolic and behavioral consequences demonstrating associations between overweight and rapid weight gain during infancy with increased risk for obesity and comorbidities later in life.

Associated with enhanced vulnerability to various cardiovascular and noncardiovascular diseases including hypertension.

Prevalence of hypertension is 36-47% in the obese population, compared with 20% normal weight individuals.

Increased body weight is a determinant of blood pressure elevation and new onset hypertension.

In 2015-2016: among children 2 to 5 years old 14% were obese and 2% severely obese; among children 6 to 11 years old, 18% were obese and 5% severely obese; and among adolescents 12 to 19 years old, 21% were obese and 8% severely obese (Hales, CM).

The average weight of women between ages 30 and 60 has increased by 20 pounds, or 14%, since 1976. Among women who weigh 300 pounds or more, the increase was 18%.

The consequence of the competitive dominance of adipocytes over other cell types in sequestering nutritional energy.

Migraine 27% more likely to occur in overweight individuals.

Estimated 13% of the world’s population is currently obese with a BMI of 30 kg/m² or greater.

Medicaid paid $8 billion for medical care related to severe obesity in 2013.

Estimated $260 billion associated with annual medical costs in 2016 for treating severe obesity.

Cost for treating severe obesity-11% paid by Medicaid, 30% paid by Medicare, 27% by private health plans and 30% paid by out-of-pocket costs.

Inpatient costs are 46% higher and spending on prescription medication is 80% higher among people with obesity than among those without overweight or obesity.

Obesity, defined as a body mass index (BMI) of ≥30 kg/m2, is associated with multiple comorbidities, including cardiovascular disease and cancer, and a higher risk of all-cause mortality.

Comorbid conditions with obesity include: asthma, type two diabetes, hypertension, obstructive sleep apnea, osteoarthritis, and cardiovascular disease.

Weight related cardiometabolic abnormalities occur due to excessive visceral adipose tissue, which secretes hormones and proinflammatory cytokines, leading to low-grade systemic inflammation.

There is a rising incidence of deaths due to obesity related cancers.

Obesity shifting cancer risks to young adults.

Excess body weight accounts for the second highest proportion of cancer cases and deaths attributable to potentially modifiable risk factors after cigarette smoking.

In 2014 it was found that 7.8% of all cancers, excluding nonmelanoma skin cancers, among adults 30 years and older were attributed to excess bodyweight, with a higher burden among women than men (Islami F).

A complex problem, affected by the interaction of biology, Behavior, social and physical environments.

The mean weight of men in the United States is now 88.3 kg and the mean weight of women is 74.7 kg (Mcdowell M et al).

3 categories: obesity 1 BMI-30-34.9, obesity 2 BMI 35-39.9 and extreme obesity BMI≥40.

From 1986-2000 prevalence of BMI of 30 or higher approximately doubled while BMI of 40 or higher quadruples and that of BMI 50 or higher increased 5 times.

Prevalence in 1960 was about 13% and by 2000 about 31% of U.S. population.

Overweight, defined as a BMI of 25.0 to 29.9 kg/m2, has been associated with an increased risk of death.

Obesity associated with 1 in 5 deaths worldwide.

In 2010 obesity estimated cause of 3.4 million deaths worldwide.

The average BMI, average waist circumference, prevalence of obesity, and prevalence of abdominal obesity increased significantly over the past 2 decades in both women and men (Ladabaum U et al).

Physical inactivity increases the risk of lumbar radicular pain in abdominally obese individuals, but not in persons with normal weight circumference.

Women gain weight with age, independent of menopausal status,and the weight increase is a result of physiologic changes of aging and lifestyle changes.

Declining daily physical activity and increasing adiposity usually occur simultaneously.

Weight gain common among women, especially during the menopausal transition.

Weight gain at midlife adversely affects emotional health, self image, and intimate partner relationships and can contribute to sexual dysfunction.

On average women gain about 1 1/2 pounds per year during midlife, independent of their initial body size or race/ethnicity.

In the US nearly 2/3 women age 40-59 years and about 3/4 of women 60 years and older are overweight.

WHO indicated that in 2008 more than 1.4 billion adults or 20% of the worlds population were overweight, and more than 500 million were obese.

Obesity prevalence in older US women is about 40 percent in women a 65-74 years and 29% of women 75 years and older.

Obese men have increased levels of inflammatory markers in their seminal fluid and lower sperm quality, both of which correlate with their body mass index (BMI):suggesting that chronic inflammation in male reproductive organs explains the link between obesity and reduced fertility.

65% of the world’s population live in countries where overweight and obesity are associated with more deaths than underweight and malnutrition.

American adults who are obese has increased 140% over the last decade.

The recommendation that we eat three meals a day with some snacking on top is mainly based on studies of diabetics, but it intermittent fasting actually improves glucose regulation.

The epidemic of obesity has occurred occurred in the past 40 years with the eating pattern of three meals a day plus snacks.

There are multiple loci, approximately 32, associated with body mass index and susceptibility to obesity..

Since 1999 the prevalence has stabilized at 35.5% in adult men, 35.8% among adults women, and 16.9% for children and adolescents.

Obesity is a risk factor for hospitalization, mechanical ventilation and mortality from H1N1 influenza.

Obesity increases duration of virus shedding of influenza A virus.

Obesity is associated with poor prognosis in patients with Covid-19.

Obese children tend to become obese adolescents, who in turn become obese adults.

National Health and Nutrition Examination Survey (NHANES) revealed in 2007-2008, 68% of US adults are overweight and 33.8% are obese: more men are obese with 72.3% compared to 64.1% for women.

National Health and Nutrition Examination Survey (NHANES) revealed in 2007-2008 indicate almost 17% of school aged children and adolescence are obese.

Children and adolescents with high body mass index often become obese adults and such adults are at risk for many chronic illnesses including diabetes, chronic kidney disease and end-stage renal disease.

As a result of obesity in adolescents type II diabetes has increased more than tenfold over the last two decades (Rocchini AP).

Previously metabolic syndrome, obstructive sleep apnea, dyslipidemia, hypertension, polycystic ovary syndrome, steatohepatitis were previously rarities and adolescents are presently commonplace as result of adolescent obesity (Daniels SR, Ludwig DS).

As the body takes in energy in the form of glucose, some is expended, and the rest is stored as glycogen, primarily in the liver, muscle cells, or as triglyceride in adipose tissue.

An imbalance in glucose intake and energy expenditure has been shown to lead to both adipose cell hypertrophy and hyperplasia, which lead to obesity.

Associated with diastolic dysfunction, autonomic tone abnormalities, atrial enlargement, a systemic pro inflammatory state all known to promote arrhythmogenesis.

Obese individuals receiving warfarin have a 40% lower risk of major bleeding compared with non-obese patients.

Fat accumulation increases total blood volume, stroke volume, cardiac output, and obesity markedly increases prevalence of hypertension and strains the left and right sides of the heart increasing prevalence of heart failure.

Obesity is a major risk factor for heart failure, particularly for heart failure with preserved ejection fraction.

Obesity and increase central body fat are associated with adverse metabolic consequences and increased risk of cardiovascular disease, which is the leading cause of death in postmenopausal women.

Abdominal subcutaneous tissue, abdominal visceral adipose tissue, intramuscular fat, intrathoracic fat, pericardial sac, thoracic peeiaortic fat, intrahepatic fat, renal sinus fat, are all individually associated with more adverse cardiometabolic risk factors.

Visceral fat linked to elevated blood pressure values and greater prevalence of hypertension, independent of total body weight and subcutaneous adiposity.

Intrahepatic fat is associated with multiple cardio metabolic risk factors.

Obese postmenopausal women have as much as a four-fold increase in cardiovascular deaths in women with a BMI greater than 29.

Obesity in the presence of increased visceral fat, increase the risk of several metabolic Health consequences including: dysglycemia or diabetes, dislipidemia, and hypertension.

Fat stores correlate with incident atrial fibrillation.

Obesity is associated with increased incidence of atrial fibrillation and venous thromboembolism.

Several studies have reported that obese patients with cardiovascular disease, heart failure, atrial fibrillation, renal disease, COPD and pulmonary embolus have a better prognosis, this so-called obesity paradox.

Life expectancy for obese adolescent individuals is reduced.

People with early rheumatoid arthritis who are overweight or obese are less likely than those of normal weight to achieve sustained remission over time.

With severe disease it is associated with significant joint pain and impaired physical function such as the ability to bend, lift, carry, push, and walk.

Excessive weight bearing leaves the joint damage and pain, resulting in restricted activity and walking limitations.

Obesity contributes to pain and physical limitations through factors such as impaired cardio respiratory function, systemic inflammation, reduce flexibility of movement, low strength per body mass, and depression.

Obesity can contribute to the development of heart failure with preserved ejection fraction (HFpEF) by two mechanisms: first, obesity triggers systemic inflammation and adipose tissue,particularly visceral fat,  is infiltrated with macrophages which release pro-inflammatory cytokines that stimulate myocardial fibrosis and endothelial dysfunction within the coronary microvasculature.

This heightened systemic inflammatory state is linked to left ventricular hypertrophy myocardial remodeling, fibrosis and increased blood vessel stiffness as is typically observed in HFpEF.

The second mechanism of obesity and heart failure with preserved ejection fraction relates to the obese have more salt retention through enhanced renal tubular sodium reabsorption.

High salt intake in patients with salt sensitive hypertension leads to systemic oxidative stress as a result of renal production of pro-inflammatory cytokines.

Obese individuals are more likely to be an active with poor functional capacity, linked to hospitalizations for heart failure in a population with coronary microvascular dysfunction.

The expanded plasma volume leads the heart to have increased chamber dilatation and within the underlying myocardial fibrosis, increased diastolic stiffness from the fibrosis, the presence of systemic inflammation and underlying ischemia during daily life the increased cardiac filling pressures can lead to heart failure without impairment of systolic function.

It is associated with increased risk of atelectasis and impaired respiratory function during general anesthesia.

Adults are more likely to have depression than those with normal weight, and 43% of adults with depression have obesity.

Obesity contributes to pain and physical limitations with impaired cardio respiratory function, systemic inflammation, reduced flexibility of movement, low strength per body mass, and depression.

There is a bidirectional association between depression and obesity, as each diagnosis is associated with increased risk of developing the other.

Additional risk factors for obesity, include insufficient sleep, and low socioeconomic status, partly mediated by chronic stress and food insecurity, which are commonly experienced by racial and ethnic minority populations.

Obesity in elderly associated with lower all- cause mortality.

Excess weight accounts for 44% of worldwide burden of diabetes, 23% of coronary artery disease, and 7-41% of cancers (WHO).

Characterized by increased levels of aldosterone.

Adipocytes can synthesize aldosterone directly, or by secreting leptin which stimulates production of aldosterone by the adrenal gland.

Obese people tend to have raised levels of the hormone leptin, which is secreted by adipose tissue and under normal circumstances increases ventilation. “

 

Rivals smoking as the most preventable cause of cancer.

Estimated 84,000 new cancer diagnoses per year and upwards of 20% of total cancer mortality associated with BMI>25 (Henley SJ et al).

Linked to 16 different types of cancer.

Associated with an increased risk of melanoma in men, and increased Breslow staging scale thickness.

Immigrants in the US gain weight in proportion to the number of years been in the US.

Twin studies demonstrate genetic influence on obesity, but no single gene explains the process.

For many weight gain occurs or accelerates following smoking cessation, the initiation of various medications, change in life events such as marriage or occupation or an illness.

Obesity at-risk times for women include pregnancy and menopause.

80% of patients with heart failure with preserved ejection failure are overweight or obese.

Maintenance of very high physical activity levels throughout young adulthood significantly reduces the risk of becoming overweight or obese.

Stressful life events can result in a change in eating in physical activity habits resulting in obesity.

Mood disorders are relatively common in patients with obesity.

Amish have only a 4% obesity rate with an average adult walking 18,000 steps per day.

Adults in US walk an average of 5100 steps per day.

Standing a quarter of the time per day or more is associated with decreased risk of obesity.

In a prospective study of 37,674 apparently healthy young men for incident angiography proven coronary heart disease and diabetes with follow up of 17.4 years: indicated an elevated BMI in adolescents constitutes a substantial risk for obesity-related disorders in midlife (Tirosh A et al).

In the above study the risk of diabetes was mainly associated with increased BMI close to the time of diagnosis, while the risk of coronary heart disease was associated with an elevated BMI both in adolescence and adulthood.

There is a graded increase in the risk of heart failure as BMI increases: for every 1 kg per meter squared increase in BMI the risk of heart failure increases 5% in men and 7% in women (Kenchaiah S et al).

Obesity has profound effects on systolic and diastolic function.

Obesity paradox is initially described the finding that obese patients undergoing percutaneous coronary intervention had lower mortality rates than normal weight counterparts (Gruberg L et al)

Obesity paradox has been noted in a range of studies of patients with and without cardiovascular disease.

Obesity increases the risk of sciatica by 31% and hospitalization for sciatica by 38%.

Obesity paradox, refers to the suggestion that obese patients with heart failure have a better prognosis than leaner patients (Lavie CJ et al, Arthram SM et al).

Individuals with an elevated BMI, compared to individuals without an elevated BMI and heart failure, have a reduction in cardiovascular and all cause mortality during a 2.7 year follow-up (Oreopoulos A et al).

The longer the duration of overall and abdominal obesity the more the association with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity (Reis JP et al).

In an in-hospital mortality study of 108,927 patients would be compensated heart failure, a higher BMI was associated with a lower mortality: a 10% lower mortality was noted for every five unit increase in BMI (Fonarow GC et al).

In 2005 60.5% of adults in the U.S. were overweight with body mass index 25-30, 23.9% obese with body mass index 31-40 and 3% extremely obese with body mass index over 40.

Associated with more than 300,000 deaths annually in the U.S. overtaking cigarette abuse as the leading preventable cause of death.

A Swedish study found that obesity in late adolescence was comparable with light smoking of 11 cigarettes/day in increasing the risk of premature death (Neovius M).

Twin studies suggest genetic factors account for 50-70% of the predisposition for the development obesity.

Increases vascular risk related mortality 1-2 fold.

Obesity related mortality is highest in men and in minority patients who have high rates of comorbid diseases.

Class I obesity defined as a body mass index (BMI: weight [kg] / height [m2]) ≥30 but <35. Class II obesity defined as a BMI ≥35 but <40. Class III obesity defined as a BMI ≥40.

The prevalence of class II and III obesity is 14.3% of the US population 20 years of age or older.

Early obesity predicts for later cardiovascular disease.

Obese have reduced ability to exercise with low functional aerobic capacity during exercise treadmill testing.

Functional aerobic capacity is a strong predictor of all- cause and cardiovascular mortality.

Bariatric surgery associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese patients (Sjostrom L et al).

In obese patients with type 2 DM 12 months of medical therapy plus bariatric surgery achieves greater glycemic control in significantly more patients than does medical management alone (Schauer PR et al).

In the above study of obese patients with poorly controlled diabetes who underwent either gastrric bypass orsleeve gastrectomy combined with medical therapy were significantly more likely to achieve hemoglobin A-1 C. levels of 6% or less one year after randomization then were patients receiving medical therapy alone.

By 2020 overall obesity and abdominal obesity are projected to affect up to 70% and 90% of black women, respectively, in the US.

Non-Hispanic blacks currently have the highest rates of obesity (48%), and risk of newly diagnosed diabetes is 77% higher among non-Hispanic blacks, 66% higher among Hispanics/Latinos and 18% higher among Asian Americans compared to non-Hispanic whites. 

More than two thirds of US adults are considered obese or overweight.

The cost of obesity-related illness approximates 20% of annual US health care spending.

As a result of obesity life expectancy could decline.

90 minutes of aerobic exercise combined with 60 minutes of resistance exercise over 3 days per week is optimum to reduce insulin resistance and improve function on previously sedentary older abdominally obese adults (Davidson).

Normal-weight women and overweight women and men have become more abdominally obese.

Estimated to be responsible for 45% of 9.3 million cases of cardiovascular disease and 280,000 annual deaths, about 13% of all deaths.

Indicates the inability for homeostatic mechanisms to offset sedentary lifestyle and excessive intake of processed high energy foods.

Associated with increase risk of hypertension, dyslipidemia, coronary artery disease, type 2 diabetes, gallbladder disease, sleep apnea and osteoarthritis.

There is a threefold higher risk for end-stage renal disease during follow-up of overweight adolescents and an almost sevenfold higher risk for obese youth (Vivante A et al).

Genetic predisposition, metabolic needs and hedonistic aspects of food ingestion important considerations to understand body weight regulation and obesity.

Pathophysiology includes genetic, behavioral, psychological and other factors.

Results from over nutrition.

Body fat accumulation occurs proportionately to the amount of excess calories consumed and is not dependent on dietary protein.

Weight loss occurs with reduced calorie intake regardless of dietary composition.

Secondary diseases increase mortality that exceeds twofold in women and 12-fold in men.

Excess weight represents the most prevalent cardiovascular risk factor in myocardial infarction.

Excess body fat effects vascular system via dyslipidemia, obstructive sleep apnea, hypertension, insulin resistance, increased leptin levels, enhanced systemic inflammation and increased free fatty acid turnover with lipotoxic effects on myocardial cells.

Obesity associated leptin and insulin production may lead to increased cell proliferation , promoting growth of cancer cells.

Obstructive sleep apnea estimated prevalence in obese adults varies from 42-48% of men and 8-38% in women (Young T et al).

After 13 weeks of aerobic exercise, with 20-40 minutes minutes per day of training improved. fitness and demonstrated dose response benefits for insulin resistance and general and visceral adiposity in sedentary overweight or obese children, regardless of sex or race (Davis CL at al). accumulation of excess body fat, but obesity is not simply excess body fat because overweight can occur from excess muscle or deposition of fat.

Predisposes to type 2 diabetes via insulin resistance, impaired glucose tolerance and pancreatic Beta-cell failure.

Adipose tissue dysfunction characterized by ectopic fat deposition in abdominal organs and liver, inflammatory and adipokine dysregulation and insulin resistance and may be an important mediator of the development of diabetes rather than total fat mass in obese individuals.

Lipid deposition into adipose tissue leads to anatomical changes, such as increased pharyngeal soft tissue, contributing to obstructive sleep apnea, or mechanical joint load that results in osteoarthritis.

50-80% of cases of diabetes attributable to obesity.

Risk of diabetes increases continuously with increasing body mass index and the relationship between obesity and diabetes is also age-dependent.

Obesity in childhood is a strong predictor of young adult obesity.

Cardiovascular risk in young adulthood is highly related to the degree of obesity as early as the age of 13.

Adolescent obesity associated with cardiovascular risk factors, orthopedic conditions, lower self-esteem, and adverse social and economic outcomes in young adulthood.

Higher rates in rural counties in the U.S.

A risk factor for colorectal cancer in men.

A cumulative lifetime exposure to excess weight may account for a large share of colorectal cancer risk, and halting and reversing the increase in prevalence of overweight and obesity may have a potential to prevent a large share of colorectal and possibly other cancers.

The risk of developing Colorectal cancer before age 50 years is nearly double for women who are obese and elevated for those who are overweight compared with women with normal body mass index.

A risk factor for pancreatic cancer.

Obesity increases risk of insulin resistance and overt diabetes and compared with normal weight individuals there is an early age of onset of pancreatic cancer and worse prognosis.

Obesity associated cancers more common in individuals over the age of 50.

Association of increased waist circumference and pancreatic cancer risk, especially in women, suggests the distribution of body fat may play a role.

Overweight and obesity associated with it the increased risk of developing breast cancer in postmenopausal women, colorectal cancer, endometrial cancer, renal cancer, adenocarcinoma of the esophagus, pancreatic cancer, and probably associated cancer of the gallbladder and liver, non-Hodgkin’s lymphoma, multiple myeloma, cancer of the cervix, ovarian cancer, an aggressive prostate cancer.

If obesity rates continues to climb, there will be an estimated half a million additional cases of cancer in the US by 2020 (ASCO).

Associated with triple negative breast cancer.

Associated with insulin resistance with elevated markers including high circulating levels of C-peptide and insulin like growth factor binding protein 1 (IGFBP1) and an association with colorectal cancer.

After 13 weeks of aerobic exercise, with 20-40 minutes minutes per day of training improved. fitness and demonstrated dose response benefits for insulin resistance and general and visceral adiposity in sedentary overweight or obese children, regardless of sex or race (Davis CL at al).

A proposed mechanism for the relationship obesity and cancer is that patients develop insulin resistance and chronic hyperinsulinemia as a result of increased free fatty acids, tumor necrosis factor alpha, and resistin and decreased release of adiponectin: Increased insulin levels and increased insulin-like growth factor1 act as growth factors and promote cell proliferation and inhibit apoptosis.

A proposed mechanism for the relationship obesity and cancer is that patients develop insulin resistance and chronic hyperinsulinemia as a result of increased free fatty acids, tumor necrosis factor alpha, and resistin and decreased release of adiponectin: Increased insulin levels and increased insulin-like growth factor1 act as growth factors and promote cell proliferation and inhibit apoptosis.

Obesity increases inflammation and desmoplasia and there is interaction of fat cells, immune cells and connective tissue cells in obese individuals stimulating a microenvironment that promotes tumor progression while blocking responses to chemotherapy.

Adiposity is associated with a relative decrease dose in chemotherapy dose intensity.

Obesity associated with increased incidence of immune related adverse events among patients receiving immune checkpoint inhibitors.

There is epidemiological and biological evidence suggesting adiposity, hyperinsulinemia, altered glucose homeostasis an elevated insulin growth hormone axis abnormalities may impair the prognosis of colorectal cancer.

Increased adiposity is associated with increased colon cancer-specific mortality.

Excess body weight increases the risk of colorectal adenomas in patients with Lynch syndrome, and this is seen only in men.

Increased adiposity associated with worse disease free colon cancer survival among women.

In women associated with a higher mortality rate for breast and cervical cancer than in thinner women.

Patients with breast, prostate and colorectal cancer who are overweight have an increased risk of cancer recurrence and death.

Postmenopausal women with obesity, BMI>30 kg/m2 at increased risk of ER positive BC.

The risk of death from all cancers combined is approximately 62% higher in women with a BMI of 40 or greater compared with normal weight women.

At time of diagnosis of prostate cancer associated with increased risk of metastases and death.

Associated with poor prognostic factors such associated high grade and non localized disease in prostate cancer.

Hiigher risk of biochemical recurrence and disease progression after radical prostatectomy for prostate cancer.

Known risk factor for postmenopausal cancer of the breast as a result circulating estrogens derived from aromatization of plasma androstenedione to estrone in adipose tissue.

A high BMI is associated with a decreased risk of premenopausal breast cancer but an increased risk for postmenopausal breast cancer (Chang S et al).

Defined as a body mass index (BMI) as weight in kg divided by the square of height in meters of over 30 or more for adults 18 years or older.

WHO classification:BMI 25 to 29.9 as class I, 30 to 34.99 as class II , and Roman numeral, III obesity is greater than 40 BMI.

A public health problem across racial, ethnic, and socioeconomic groups.

African Americans, Hispanics, those with lesser education, older persons, and some US states are affected disproportionally.

33% of African American women and 17% of white women are obese with a body mass index greater than 30.

African Americans have the highest prevalence at 33.9%.

69% of African-American men and 81% of African Women are overweight (Ogden CL).

In U.S. s have a 51% higher prevalence of obesity and Hispanics have a 21%, higher obesity prevalence compared with whites.

Approximately 65% of individuals over the age of 20 years in the U.S. have a BMI of 25 or greater and are defined as overweight, of that number 30% are obese with a BMI of 30 or greater with 5% are extremely obese with a BMI of 40 or greater.

European Prospective Investigation into Cancer and Nutrition (EPIC) followed 14,723 participants for a mean 9.7 years revealed that general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.

Waist circumferance of more than 40 inches in men or 35 inches in women associated with increased risks for type 2 diabetes, hypertension, and coronary artery disease.

The risk of death from any cause among black women increases with increasing BMI of 25.0 or higher, and is similar to the pattern among whites.

Waist circumference is associated with increased of death among non-obese women.

EPIC study associated the BMI with the risk of death as J-shaped, with higher risks of death in the lower and upper BMI categories than in the middle categories.

Approximately one third of Americans overweight, one third obese and 4.5% have extreme obesity.

16% of children between 6 and 19 years of age are overweight.

10.3 percent of African American women are extremely obese defined as a BMI of 40 or more compared to 6.2 percent of white women.

Obese individuals who are physically active have a lower incidence of developing many chronic diseases, compared with unfit obese counterparts.

Physical activity at maintained at high levels through young adulthood may lessen weight gain as young adults transition to middle age, and this is particularly true for women (Hankinson AL et al).

May be the most important risk factor for osteoarthritis of the knee.

The likelihood of conceiving steadily decreases as BMI increases.

Confers a relative pulmonary embolism risk of 3.4 in the Nurses Health Study.

Accounts for approximately 6% of expenditures for healthcare in the U.S.

Gastric bypass produces about a 10% greater weight loss over 8 years than to other surgical procedures.

15% of adults over the age of 70 years.

Obesity-increases the risk of kidney disease.

Mild to moderate overweight status in the elderly does not confer an excess mortality risk.

May be protective compared to thinness of normal weight in older community-dwelling individuals.

Increased risk for complications for patients undergoing surgery with problems ranging from cardiac ischemia, pulmonary embolism, nausea, vomiting, wound infections, wound dehiscence, and incision hernia.

Associated with problems related to upper airway access and maintaining ventilation with surgery.

Not associated with unplanned admissions to the hospital after ambulatory surgery, suggesting obesity should not prevent such procedures (Hofer).

In adults, disease risk increased independently with increasing BMI and excess abdominal fat.

Cardiovascular and other obesity-related disease risks increase significantly when BMI exceed 25.0 kg per meter square.

Overall mortality increased most dramatically as BMI surpasses 30 kg per meter square.

Obesity mortality increases logarithmically for body mass indices that exceed 30.

Associated with sexual maturation among adolescent girls and young female adults.

Obesity associated with Cushing’s syndrome, hypothyroidism, leptin gene mutation, and congenital syndromes such as Prader-Willi.

Weight gain promoted by antidepressant drugs, antiepleptic agents, sulfonylureas, and corticosteroids.

Waist circumference measurements greater than 40 inches in men and 35 inches in women indicate an increased risk of obesity-related comorbidities.

Even a small weight loss as little as 10% of initial body weight in overweight and obese adults reduces various chronic disease risk factors such as hypertension, hyperlipidemia, and hyperglycemia.

Central obesity with waist:hip ration greater than 0.8 associated with a disproportionate increase in coronary risk.

Sarcopenic obesity-weight gain without concurrent gains in lean body mass.

Sarcogenic obesity-gradual obesity associated with increased age and menopause.

Acute sarcopenic obesity-observed in corticosteroids use, hypopituitarism, hypogonadism and prolonged physical inactivity or bed rest.

More than 90% of seriously obese individuals will regain their weight after it is lost with dieting.

Hypoventilation syndrome-patients are older than patients with pure obstructive sleep apnea.

Hypoventilation syndrome-mild to moderate restrictive ventilatory pattern due to obesity with gas exchange impairment and pulmonary hypertension being quite frequent.

Hypoventilation syndrome-frequently associated with obstructive sleep apnea.

A genetic contribution is supported by the findings of greater similarity of body mass between monozygotic vs dizygotic twins and correlation of BMI with biological but not adoptive parents.

Contributes to endothelial dysfunction, hyperinsulinemia and elevated C-reactive protein.

Adenocarcinoma of the esophagus, gastric cardia, hepatic necrosis, cirrhosis, cholecystitis, reflux esophagitis associated with obesity.

Gastric cardia, or upper stomach cancer, is associated with a higher risk due to obesity.

For every kilogram increase in BMI there is a 4% increased risk of developing gastric cardia cancer.

Obesity among never smokers is independently associated with twofold worsening of disease specific survival, disease free survival, and overall survival after surgery for esophageal adenocarcinoma.

Obesity-in childhood and adolescence is a predictor of the eventual development of diabetes, hypertension, dyslipidemia and cardiovascular disease in adulthood.

More than 75% of patients with hypertension accounted for by obesity.

Risk of death from all causes, cancer and cardiovascular diseases increases throughout the ranges of obesity.

Cardiovascular mortality related to obesity in the US population over the past 2 decades has been increasing: in contrast to general cardiovascular mortality trends, which have steadily declined over the same time period. 

Black individuals, in particular women have been  disproportionately impacted. 

American Indian or Alaska Native individuals as a cohort in whom the risk of obesity‐related cardiovascular mortality is rising most rapidly. 

Nonsurgical weight loss by lifestyle interventions combined with anti-obesity medications have had no affect on primary cardiovascular end points.

A meta-analysis genomewide association studies as established 32 loci associated with a BMI.

In an analysis of genetic predisposition and intake of sugar sweetened beverages in relation to BMI and obesity risk in 6930 for women from the Nurses” Health Study, and 4423 men from the Health Professionals Followup Study and a cohort of 21,740 women from the Women’s Genome Health Study: Blood genetic association with obesity is more pronounced with grade intake of sugar-sweetened beverages (Qibin Qi et al).

Virtually all patients have an increased leptin levels.

Endometrial cancer, of all malignancies, most associated with obesity.

Obesity, accounts for approximately 60% of cases of endometrial cancer.

Increases risk of left ventricular hypertrophy.

Trauma in obese patients associated with higher morbidity and mortality.

There are reported increases in the incidence of cardiovascular, pulmonary, venous thromboembolic, and infectious complications in obese trauma patients (Lazar MA).

Obese patients who sustain high-energy traumatic injuries often sustain orthopedic injuries to the pelvis or lower extremities.

Obese orthopedic trauma patients may be at higher risk for nerve injuries secondary to positioning, intraoperative complications, loss of reduction after surgery, increased intraoperative estimated blood loss, and increased operative times (Lazar MA).

Decreases the cardioprotective levels of high-density lipoprotein cholesterol.

Associated with propensity for complex dysrhythmias.

Generally, a decrease in body weight of 1% associated with a systolic blood pressure decrease by 1 mm Hg and a diastolic blood pressure drop of 2 mm Hg.

Among 20-30 year-olds associated with a decreased life expectancy of 5 years among black women, 8 years for white women, 13 years for white men and 20 years for black men.

Weight gain associated with insulin, Sulfonylureas, antidepressants and Beta-adrenergic receptor blockers.

Medical spending for obesity related conditions estimated to be 10% of total annual U.S. medical expenses in 2008 or $147 billion (CDC).

In 2006 the annual spending for obese people was 42% greater than spending for normal weight people.

Despite adverse effects of obesity on coronary heart disease, coronary risk factors, plasma lipids, inflammation, glucose abnormalities, insulin resistance, metabolic syndrome, type II diabetes, and LVH, many studies have demonstrated an inverse relationship exists between obesity, generally determined by body mass index on mortality is referred to as the obesity paradox.

Obesity paradox has been demonstrated in non-cardiovascular studies that included patients with renal disease and an elderly cohort.

The obesity paradox has been demonstrated in a large meta-analysis with 40 cohort studies and more than 250,000 patients with coronary artery disease (Romero-Corral A et al).

The obesity paradox may be related to the fact that BMI does not always reflect true body fatness, and that defining obesity by weight circumference, waist/hip ratio, percent body fat may be more accurate.

In cohorts with established cardiovascular diseases that include hypertension, atrial fibrillation, peripheral arterial disease, coronary artery disease patients with obesity have better clinical prognosis than do their lean counterparts, termed obesity paradox.

In an analysis of all cause mortality in patients with coronary artery disease, patients with low BMI have the highest mortality, whereas obese patients had lower risk (Romero-Corral et al)

In the above analysis overweight patients had lowest relative risk in their adjusted analysis, whereas obese and severely obese patients had no increased risk: obesity paradox.

Obesity and abdominal obesity are associated with morbidity and mortality, independently.

Physical activity attenuates risks of morbidity and mortality for obesity and abdominal obesity.

Trends in obesity prevalence in US adults may be stabilizing.

In obese adolescents liraglutide plus lifestyle therapy lead to significant greater reductions in BMI than placebo plus lifestyle therapy. (Kelly AS).

 

Semglutide and other GLP-1 (Glucagon like peptide 1) agents provide weight loss by improved appetite control, reduced energy intake via the hypothalamus and area post stream of the brain.

 

Among adults with overweight or obesity completing a 20 week run in ofsubcutaneous semaglutide results and continued weight loss.

Among patients with obesity, bariatric surgery is associated with a longer life expectancy than usual obesity care.  

Reduced calorie intake of 500 to 750 kcal per day deficit is advised for weight reduction. 

Institution of portion control, reduction or elimination of ultraprocessed foods and increased fruit and vegetable intake are recommended for obesity management.

The DASH is suggested with high protein shakes or bars to replace meals can improve weight loss.

physical activity has a modest affect on weight loss, and it is not used as a standalone obesity treatment, but helps with weight weight maintenance and cardio metabolic health.

Moderate intensity aerobic exercise is associated with decreased visceral adiposity, and modest weight loss.

Resistance training  preserves the lean/fat free mass during weight loss.

All obese patients should participate in 150 to 300 minutes per week of moderate or 75 to 150 minute per week of vigorous physical activity as well as resistance training 2 to 3 times a week.

 

 

 

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