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Monday, August 11, 2025

Obesity


Introduction
Obesity is a chronic, multifactorial disease characterized by an excess accumulation of body fat that poses a risk to health. It results from an imbalance between caloric intake and energy expenditure, influenced by genetic, environmental, behavioral, and metabolic factors. It is associated with increased morbidity and mortality and contributes significantly to the global burden of noncommunicable diseases.

Epidemiology

  • Prevalence has tripled globally since 1975, affecting both developed and developing countries.

  • Affects all age groups, including children and adolescents.

  • Body mass index (BMI) is used to define obesity:

    • BMI 25–29.9 kg/m²: Overweight

    • BMI ≥30 kg/m²: Obese

      • Class I: 30–34.9 kg/m²

      • Class II: 35–39.9 kg/m²

      • Class III (morbid obesity): ≥40 kg/m²

  • Obesity is more prevalent in urban areas, and rates are generally higher among women than men.

Etiology and Risk Factors

Genetic factors

  • Polymorphisms in genes regulating appetite and energy balance (e.g., leptin, melanocortin-4 receptor).

  • Familial predisposition increases risk.

Environmental and lifestyle factors

  • High-calorie diets, processed foods, sugar-sweetened beverages.

  • Sedentary lifestyle and reduced physical activity.

  • Disrupted sleep patterns.

Medical and endocrine causes

  • Hypothyroidism, Cushing’s syndrome, polycystic ovary syndrome (PCOS), hypothalamic disorders.

Medications

  • Antipsychotics (olanzapine, clozapine).

  • Antidepressants (mirtazapine, tricyclics).

  • Anticonvulsants (valproate).

  • Corticosteroids.

Pathophysiology
Obesity results from prolonged positive energy balance. Key mechanisms include:

  • Dysregulation of appetite and satiety pathways in the hypothalamus.

  • Increased insulin resistance and hyperinsulinemia.

  • Adipose tissue dysfunction, with increased pro-inflammatory cytokines (TNF-α, IL-6).

  • Altered gut microbiota composition affecting metabolism.

Complications

Metabolic:

  • Type 2 diabetes mellitus.

  • Dyslipidemia.

  • Metabolic syndrome.

Cardiovascular:

  • Hypertension.

  • Coronary artery disease.

  • Stroke.

Respiratory:

  • Obstructive sleep apnea.

  • Obesity hypoventilation syndrome.

Musculoskeletal:

  • Osteoarthritis.

  • Chronic back pain.

Gastrointestinal and hepatobiliary:

  • Non-alcoholic fatty liver disease (NAFLD).

  • Gallstones.

Endocrine/reproductive:

  • Infertility.

  • Menstrual irregularities.

Cancer risk:

  • Increased risk of breast, endometrial, colorectal, pancreatic, and esophageal cancers.

Diagnosis

  • Anthropometric measurements: BMI, waist circumference (≥94 cm in men, ≥80 cm in women indicates increased risk), waist-to-hip ratio.

  • Body composition analysis: Bioelectrical impedance, DEXA scan.

  • Laboratory investigations: Lipid profile, fasting glucose/HbA1c, liver function tests, thyroid function tests.

Management

1. Lifestyle Modification – First-Line Therapy

  • Dietary changes:

    • Calorie deficit of 500–1000 kcal/day for gradual weight loss of 0.5–1 kg/week.

    • Emphasis on whole grains, lean proteins, fruits, vegetables, and healthy fats.

    • Limit intake of processed foods and sugar-sweetened beverages.

  • Physical activity:

    • At least 150–300 minutes/week of moderate-intensity exercise.

    • Resistance training 2–3 times per week.

  • Behavioral therapy:

    • Goal setting, self-monitoring, stimulus control, and stress management.

2. Pharmacological Therapy (Adjunct to lifestyle changes; indicated for BMI ≥30 kg/m², or ≥27 kg/m² with comorbidities)

Approved Medications and Doses:

  • Orlistat: 120 mg orally three times daily with main meals containing fat.

    • Mechanism: Inhibits gastrointestinal lipases, reducing fat absorption.

    • Side effects: Steatorrhea, flatulence, fat-soluble vitamin deficiency.

  • Liraglutide (GLP-1 receptor agonist): Start 0.6 mg subcutaneously daily, increase weekly by 0.6 mg to 3 mg daily.

    • Mechanism: Increases satiety, delays gastric emptying.

    • Side effects: Nausea, vomiting, pancreatitis risk.

  • Semaglutide (GLP-1 receptor agonist): Start 0.25 mg subcutaneously weekly, titrate to 2.4 mg weekly.

  • Phentermine: 15–37.5 mg orally daily before breakfast (short-term use, ≤12 weeks).

    • Mechanism: Sympathomimetic appetite suppressant.

    • Side effects: Insomnia, palpitations, increased BP.

  • Phentermine/topiramate extended-release: Start 3.75 mg/23 mg daily, titrate to 15 mg/92 mg daily.

  • Naltrexone/bupropion extended-release: Start 8 mg/90 mg daily, titrate weekly to 32 mg/360 mg daily.

3. Bariatric Surgery (Indicated for BMI ≥40 kg/m² or ≥35 kg/m² with comorbidities when other measures fail)

  • Procedures: Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding, biliopancreatic diversion.

  • Requires long-term nutritional monitoring and lifestyle adherence.

4. Long-Term Maintenance

  • Ongoing dietary and exercise program.

  • Regular follow-up to prevent weight regain.

  • Psychological support and treatment of comorbid mental health conditions.

Prognosis

  • Weight loss of 5–10% can significantly improve metabolic health and reduce cardiovascular risk.

  • Without intervention, obesity often persists and worsens, increasing complication risk.




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