Obesity

Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Several conditions are associated with obesity, including diabetes, hypertension, and heart disease, all of which contribute to significant healthcare costs. Diagnosis is most commonly based on BMI measurement, wherein obesity is defined as BMI > 30. Management includes lifestyle changes, medications, or, in severe cases, bariatric surgery.

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Overview

Definition

Obesity is a condition associated with excess body weight, specifically with excessive adipose tissue deposition.

Obesity measurements

  • Obesity can be precisely defined by BMI or body fat percentage.
  • Waist circumference is a measure of abdominal obesity and is associated with increased cardiovascular risks.
  • BMI is calculated as weight (kg)/height² (m²).
  • BMI classification:
    • Underweight < 18.5
    • Normal weight: 18.5–24.9 
    • Overweight: 25–29.9
    • Obesity: 30–39.9
    • Morbid obesity: > 40
  • Body fat percentage = 1.2(BMI) + 0.23(age) – 10.8(sex) – 5.4:
    • Normal:
      • Men (sex = 1): 15%–20%
      • Women (sex = 0): 25%–30%
    • Obesity:
      • Men: > 25%
      • Women: > 33%
  • Waist circumference indicating increased cardiac risk:
    • Men: > 102 cm
    • Women: > 88 cm

Body mass index chart

Image by Lecturio.

Epidemiology

  • ⅓ or more adults in the United States suffer from obesity.
  • Prevalence appears to be steadily increasing and shows a slightly increased prevalence in women compared to men.
  • There was an increase in the prevalence of obesity from 19.4% in 1997 to 31.4% in 2017.
  • About 17% of children and adolescents are affected.
  • In 2015, approximately 108 million children and 604 million adults globally were obese.

Etiology

The nature of obesity is believed to be multifactorial. Sedentary lifestyle and increased caloric intake appear to be the most common causes.

Causes can be further categorized by:

  • Dietary factors: overeating, high-fat diets
  • Social/behavioral factors: socioeconomic factors, psychological factors, night eating, binge eating
  • Sedentary lifestyle: poor exercise habits and sedentary jobs; inactivity due to surgery, disability, or aging
  • Iatrogenic: due to certain medications or hypothalamic surgery
  • Genetic conditions
  • Underlying neuroendocrine disorders: Cushing’s syndrome, hypothyroidism, growth hormone deficiency, hypogonadism

Medications associated with weight gain include:

  • Steroids (prednisone)
  • Diabetes medications (insulin, sulfonylureas, thiazolidinediones)
  • Antipsychotics (risperidone, quetiapine, olanzapine)
  • Antidepressants (paroxetine, citalopram, amitriptyline, mirtazapine)
  • Mood stabilizers/neurological agents (carbamazepine, valproate, lithium, gabapentin)
  • Hormonal agents/progestins (medroxyprogesterone)
  • Beta-blockers (propranolol)
  • Alpha-blockers (terazosin)

Pathophysiology and Obesity-related Morbidity

Pathophysiology

  • Obesity may be hypertrophic (increased size of adipocytes) or hypercellular (increased number of cells):
    • The hypertrophic variant is typical of android (abdominal) obesity.
    • The hypercellular variant is frequently associated with childhood and very severe obesity.
  • A number of hormones are involved in the regulation of appetite, satiety, metabolism, and fat distribution.
  • Orexigenic hormones involved in appetite stimulation include ghrelin, endocannabinoid, and neuropeptide Y.
  • Anorexigenic hormones involved in appetite suppression include leptin, GLP-1, and peptide YY.
  • 2 hormones that likely play the biggest role in regulation of appetite and body weight are ghrelin and leptin: 
    • Ghrelin:
      • Mainly produced in the stomach
      • Sends signals to the lateral nucleus of the hypothalamus (hunger center) to ↑ appetite and stimulate hunger 
      • Levels ↑ during starvation/fasting and sleep deprivation
      • Levels ↓ after food intake
    • Leptin:
      • Primarily produced by adipose tissue
      • Sends signals to the ventromedial nucleus of the hypothalamus (satiety center) to decrease appetite
      • Opposes ghrelin by signaling the sense of satiety to the hypothalamus
      • Levels ↑ with food intake and with ↑ in weight and body fat due to increasing leptin resistance
      • Levels ↓ with starvation, sleep deprivation, and exercise

Obesity-associated morbidity

Obesity is associated with increased mortality and negatively impacts almost every organ system. Abdominal obesity is specifically associated with increased cardiovascular risks.

Commonly observed effects include:

  • Cardiovascular:
    • Coronary artery syndrome
    • Hypertension
    • Cardiomyopathy
    • Ventricular hypertrophy
    • Heart failure
    • Varicose veins
    • Deep vein thrombosis
  • Respiratory:
    • Obstructive sleep apnea
    • Asthma
    • Respiratory infections
    • Obesity hypoventilation syndrome
  • Neurological:
    • Increased risk of hemorrhagic and ischemic stroke in men
    • Meralgia paresthetica (compression of the lateral cutaneous nerve of the thigh)
  • Genitourinary/reproductive:
    • Polycystic ovarian syndrome (PCOS)
    • Macrosomic babies and subsequent pelvic dystocia
    • Stress incontinence
  • Skin:
    • Increased risk of infection and cellulitis due to poor circulation
    • Acanthosis nigricans secondary to metabolic changes
  • Endocrine/metabolic:
    • Type 2 diabetes mellitus
    • Metabolic syndrome
    • Dyslipidemia
    • Hypercholesterolemia
  • GI: 
    • Gallbladder disease
    • GERD
  • Musculoskeletal: knee osteoarthritis
  • Hematology/oncology:
    • Lymphadenopathy
    • ↑ Risk for lung, pancreatic, renal, and gastric cancers in both genders
    • ↑ Risk for endometrial, ovarian, and breast cancers in women
    • ↑ Risk for prostate, colon, and rectal cancer in men

Diagnosis

History

  • Identify factors contributing to obesity:
    • Lifestyle (occupation, exercise)
    • Diet/caloric intake
    • Duration of a problem/age of onset
    • Previous weight-loss attempts
    • Smoking cessation (may stimulate increased caloric intake)
    • Family history
  • Rule out secondary causes:
    • Medications (e.g., steroids, antipsychotics)
    • Diseases:
      • Hypothyroidism
      • Cushing’s syndrome

Physical exam

  • Individuals should be screened to obtain BMI measurements.
  • There are some caveats in using BMI: 
    • BMI does not account for the percentage of weight that is muscle versus fat, and may overestimate adiposity in muscular individuals (i.e., athletes, bodybuilders).
    • BMI may underestimate adiposity in individuals, such as the elderly, who may have lost muscle mass secondary to aging.
    • BMI does not take into account the distribution of body fat, such as abdominal obesity, which is a risk factor in itself.
  • Body-fat percentage may be a more accurate tool to evaluate muscular individuals.
  • Waist circumference should be measured in individuals having BMI ranging from 25–35 to assess abdominal adiposity.

Abdominal obesity

Image: “Belly of an obese teenage boy” by OctoMocto. License: Public Domain

Laboratory workup

  • Fasting glucose and/or HbA1c
  • Thyroid-stimulating hormone (TSH)
  • Liver enzymes
  • Fasting lipids
  • Cholesterol
  • Further tests should be performed if history, exam findings, or initial labs raise suspicion of secondary causes:
    • Growth hormone levels
    • Adrenocorticotropic hormone/cortisol

Management

Goals of treatment

  • To prevent, treat, or reverse obesity-related morbidity
  • Weight loss of 5%–7% of body weight is associated with reducing the risk of diabetes, hypertension, and dyslipidemia.
  • In individuals with BMI > 30, weight loss of approximately 25 lbs is associated with a reduced risk of cardiovascular disease, cancer, and overall mortality.

Lifestyle/behavior modifications

  • 1st step in the management of obesity 
  • Dietary changes:
    • Decreasing caloric intake relative to caloric expenditure
    • Recommended caloric intake for weight loss: 800–1200 kcal/day
    • Specific type of diet not as important, but overall healthier food choices should be recommended
  • Increase physical activity/exercise 
  • Behavior therapy/modification:
    • Recommended to help patients make long-term changes 
    • Encourage patients to modify and monitor food intake and physical activity, and increase awareness of triggers that stimulate eating.
    • Create short-term realistic goals to change patient behaviors and develop a plan for accomplishing goals.
  • Patient education:
    • Educate the patient about the risks and benefits associated with their weight and lifestyle habits.
    • Counsel patients on healthier nutrition habits and choices of physical activity.

Medications

Weight-loss medications are reserved for patients who have:

  • Failed to lose > 5% total body weight within 3–6 months after modifications in lifestyle behavior alone, AND have
  • BMI of ≥ 27 with comorbidities 
  • BMI of 30 with or without comorbidities

Considerations and results:

  • Use of medications for weight loss typically results in a weight loss of 4%–8% of body weight over a period of 6–12 months.
  • Combining lifestyle/behavioral changes with weight-loss medications results in greater weight loss than with medications alone.
  • Choice of the anti-obesity agent is based on the comorbidities and relative contraindications relevant to the patient.
  • Weight loss, blood pressure, and heart rate of the patient should be closely monitored for the duration of medical management.
  • Discontinuation of weight-loss medications has been associated with regaining weight.

Duration: 

  • If the patient does not lose 4%–5% baseline body weight by 12 weeks at the maximum tolerated dose, the medication should be tapered and discontinued.
  • Continuation of weight-loss medications for long-term use may be considered if:
    • Medication has been well-tolerated
    • At least 5% of weight reduction from baseline has occurred and lasted 6 months after starting medication
  • The following medications are approved for short-term use (< 12 weeks):
    • All noradrenergic sympathomimetic agents
    • Controlled substances with amphetamine-like effects and potential for abuse:
      • Phentermine
      • Benzphetamine
      • Diethylpropion
      • Phendimetrazine
    • The following medications are approved for long-term use in weight-loss management:
      • Liraglutide (Victoza)
      • Orlistat
      • Phentermine-topiramate
      • Naltrexone-bupropion

Medications may also be needed to manage comorbidities such as hypertension, diabetes, hyperlipidemia, and depression:

  • If possible, avoid medications associated with weight gain.
  • Select medications that may also result in weight loss.
  • Examples of medications that may aid weight loss:
    • Metformin or semaglutide (Ozempic) used in the management of diabetes
    • Fluoxetine (Prozac) used in the management of psychiatric disorders

Bariatric surgery

  • Weight loss of up to 40% of baseline weight may be seen at 12–18 months after the procedure.
  • Indications:
    • BMI > 40 kg/m2
    • BMI > 35 kg/m2 with co-morbidities of obesity (hypertension, severe diabetes, sleep apnea, osteoarthritis)
    • BMI > 30 kg/m2 with type 2 diabetes, refractory to treatment measures or dysmetabolic syndrome X
    • Failure of conservative attempts at weight loss 
  • Psychological screening recommended before undergoing surgery
  • Best means to cure obesity-related complications (hypertension, diabetes)
  • Surgical options:
    • Sleeve gastrectomy 
    • Roux-en-Y gastric bypass 
    • Laparoscopic gastric band
    • Intragastric balloon

Clinical Relevance

Secondary causes of obesity

  • Hypothyroidism: a condition caused by the deficiency of T3 and T4. Clinical features of hypothyroidism reflect the effects of decreased metabolic rate and include fatigue, bradycardia, cold intolerance, and weight gain. Diagnosis is based on thyroid function tests. Elevated thyroid stimulating hormone and low free thyroxine (T4) are noted. Treatment is with synthetic T4.
  • Cushing’s syndrome: a disorder that occurs due to hypercortisolism. Cushing’s syndrome may result from the excessive use of corticosteroids or something in the body that produces excess cortisol. Clinical features include central obesity, round moon face, hump of fatty tissue on the upper back/neck, abdominal striae, and easy bruising. Cushing’s syndrome is associated with hypertension and hyperglycemia. Diagnosis is based on the measurement of cortisol levels. Treatment depends on the cause of the excess level of cortisol. 
  • Prader-Willi syndrome: a rare genetic neurodevelopmental disorder. Prader-Willi syndrome is associated with hypotonia, short stature, intellectual disability, and obesity. Extremely high ghrelin levels in patients are hypothesized to be culpable for obesity, hyperphagia, and voracious appetite. Genetic testing confirms the diagnosis. A multidisciplinary treatment approach includes weight management, a range of therapies (i.e., physical, language, behavioral), and condition-specific treatments. 

Disorders related to obesity

  • PCOS: a common endocrine disorder affecting reproductive-aged women. Polycystic ovarian syndrome is characterized by hyperandrogenism, irregular menstrual cycles, and metabolic dysfunction, and is known to increase the risk of infertility and cardiovascular disease. Etiology is uncertain but genetics and excess hormone levels are believed to play a role. Diagnosis is based on exclusion. Management includes attempting to restore normal ovulation through weight loss, oral contraceptive pills, and assistance with fertility.
  • Metabolic syndrome: a group of health problems that includes hypertension, impaired fasting glucose levels, dyslipidemia, and a large waist circumference. Patients are characteristically overweight with predominant central (abdominal)-fat distribution. Diagnosis is made based on the presence of the above conditions after exam and blood tests. Management involves lifestyle changes and medications to manage associated health problems. 
  • Diabetes mellitus type 2: a metabolic disorder characterized by chronic hyperglycemia with elevated urine sugar. Type 2 diabetes mellitus results from insulin resistance in tissues and/or the inability of the pancreas to synthesize adequate insulin. Symptoms include increased thirst, frequent urination, increased hunger, fatigue, and paresthesias. Blood tests are used to confirm the diagnosis. Management involves lifestyle changes and medications. 
  • Obstructive sleep apnea: a condition characterized by episodic apnea or cessation of breathing during sleep, wherein the period of apnea lasts > 10 seconds. Obstructive sleep apnea results from a partial or complete collapse of the upper airway and is associated with snoring, restlessness, daytime headache, and somnolence. A sleep study is used to confirm the diagnosis. Management involves weight loss and the use of devices, such as a continuous positive airway pressure (CPAP) machine, which helps keep the airway open. 
  • Meralgia paresthetica: a condition caused by compression of the lateral femoral cutaneous nerve, which supplies sensation to the upper lateral thigh. Meralgia paresthetica is marked by tingling, numbness, and burning pain in the outer part of the upper lateral thigh and is common in individuals with high BMI. Diagnosis is based on history and exam, although tests may be conducted to rule out other conditions. Management involves weight loss, drug therapy, steroid injections, and in rare cases, surgical decompression.

References

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