Understanding Obesity: Causes, Effects, and Treatment

Posted on Sep 27, 2024 in Medicine & Health

What Happens if You Lose 10 kg?

  • 15% decrease in LDL cholesterol levels
  • 8% increase in HDL cholesterol
  • Blood pressure decrease: For every 1% reduction in weight, blood pressure decreases 1-2mm Hg. This effect is amplified with exercise.

Objectives in Obesity Treatment

  • Modest weight loss: Even 5-10% weight loss can significantly improve obesity-related complications.
  • Weight maintenance: Focus on maintaining the achieved weight loss for long-term health benefits.

Options for Obesity Treatment and Control

Losing 10% of excess weight offers substantial health benefits. Treatment options include:

  • Diet and exercise programs
  • Lifestyle and behavior changes
  • Medical treatment
  • Surgical treatment

Classification of Obesity Drugs

Obesity drugs are classified by their mechanism of action:

  1. Appetite suppressants:
    • Noradrenergic agents
    • Serotonergic agents
  2. Nutrient absorption reducers: Orlistat (Xenical)
  3. Energy expenditure increasers: Ephedrine, xanthines (caffeine, theophylline), and thyroid hormone
  4. Fat cell size reducers: Drugs that promote fatty acid oxidation.

When is Surgical Treatment Used?

Surgery is considered for individuals with:

  • Morbid obesity (BMI > 40)
  • Less severe obesity with serious or life-threatening complications
  • Ineffective long-term results from diet, exercise, and medication

Surgery can lead to significant and sustained weight loss (often > 5 years).

Fat Absorption Requirements

Lipases are essential for converting triglycerides into fatty acids, enabling fat absorption.

Lipolytic Enzymes

Humans have four lipolytic enzymes:

  • Gastric lipase
  • Pancreatic lipase (most important)
  • Carboxylester lipase
  • Phospholipase A2

What is Orlistat?

Orlistat, also known as tetrahydrolipostatin, is an FDA-approved drug for weight loss. It inhibits fat absorption, reducing caloric intake.

Mechanism of Action of Orlistat

Orlistat is a potent, specific, irreversible, and long-acting inhibitor of gastrointestinal lipases. It acts in the stomach and small intestine, blocking lipase action and reducing fat absorption by approximately 30%.

Systemic Absorption of Orlistat

Orlistat has negligible systemic absorption, with sporadic and low plasma concentrations (<10 ng/mL) even after long-term use.

Elimination of Orlistat

Orlistat is primarily eliminated through fecal excretion (97%), with 83% as unchanged drug. Renal excretion is minimal (<2%).

Fat Excretion with Orlistat

Fecal fat excretion is dose-dependent, reaching a maximum of 30% with 360 mg/day. Higher doses do not significantly increase fat excretion.

Weight Loss with Orlistat vs. Diet Alone

Orlistat, combined with diet, resulted in 10% or more weight loss in 60% of patients, compared to 33% with diet alone.

Importance of Early Obesity Management in Adolescents

Early obesity management is crucial as excess weight in adolescents increases the risk of high blood pressure, high cholesterol, type 2 diabetes, and early mortality in adulthood.

Orlistat Use in Adolescents

Orlistat was approved for use in adolescents (12-16 years) by the FDA in December 2003.

Orlistat’s Effects on Glucose Metabolism

Obesity is a major risk factor for type 2 diabetes. A 1% decrease in HbA1c is associated with significant reductions in microvascular complications, myocardial infarction incidence, and diabetes-related deaths.

Orlistat and Diabetes Prevention

The XENDOS study (2004) showed that orlistat, combined with lifestyle changes, reduced the risk of developing type 2 diabetes by 37%.

Additional Glycemic Control Factors with Orlistat

Besides weight loss, orlistat’s anti-hyperglycemic effects may be attributed to:

  • Decreased circulating free fatty acids
  • Enhanced incretin secretion (GLP-1)

Orlistat’s Effects in Diabetic Patients

Orlistat improves cardiovascular risk parameters in diabetic patients, including fasting blood glucose and HbA1c, beyond weight reduction.

Orlistat’s Effects on Blood Pressure

Orlistat contributes to blood pressure improvement in obese individuals, especially when combined with exercise. It may also reduce the need for antihypertensive medication.

Orlistat’s Effects on Inflammation Markers

Studies have shown that orlistat can reduce levels of inflammatory markers associated with metabolic syndrome, such as cytokines, C-reactive protein, leptin, and TNF-α, while increasing adiponectin.

Orlistat’s Effects on Postprandial Lipemia

By blocking lipase and inhibiting fat absorption, orlistat reduces postprandial hyperlipidemia and indirectly interferes with cholesterol absorption.

Orlistat’s Effect on Waist Circumference

Orlistat has been associated with a greater reduction in visceral fat (44% higher) compared to the same weight loss achieved without orlistat.

What is L-Carnitine?

L-carnitine is a low molecular weight amino acid derivative and cofactor in fatty acid metabolism, synthesized from methionine and lysine.

Mechanism of Action of L-Carnitine

L-carnitine transports free fatty acids into mitochondria for beta-oxidation, where they are broken down into acetyl-CoA, which enters the Krebs cycle to produce energy (ATP).

Benefits of L-Carnitine Supplementation

Exogenous L-carnitine increases systemic and hepatic carnitine levels, potentially enhancing fatty acid utilization, increasing energy availability, and preserving muscle protein during fasting or exercise.

L-Carnitine and Weight Control

L-carnitine supplements may support weight loss programs by promoting optimal fat oxidation when combined with calorie reduction and exercise.

L-Carnitine and Exercise

L-carnitine can improve exercise capacity, oxygen consumption, reduce fatigue, and enhance muscle conditioning.

L-Carnitine and Cardiovascular Health

L-carnitine is crucial for cardiovascular health, as the heart derives about 70% of its energy from fat breakdown. Supplements may benefit heart muscle and viability.

Aliduet Pharmaceutical Form and Formulation

Each capsule contains:

  • Orlistat 60 mg / 120 mg
  • L-Carnitine Tartrate 600 mg

Aliduet Therapeutic Indications

Aliduet, in conjunction with a hypocaloric diet, is indicated for long-term weight control (reduction, maintenance, and prevention of weight regain) in obese or overweight patients, including those with obesity-related risk factors. It also improves risk factors like hypercholesterolemia, glucose intolerance, type 2 diabetes, hypertension, hyperinsulinemia, and visceral fat.

Aliduet Contraindications

  • Chronic malabsorption syndrome
  • Hypersensitivity to any component

Aliduet Precautions

  • Increased gastrointestinal events with high-fat diets
  • Dosage adjustments of oral hypoglycemic medication may be needed in type 2 diabetes
  • Reduced cyclosporine plasma levels
  • Reduced systemic exposure to amiodarone

Aliduet Side Effects

Side effects are primarily gastrointestinal, related to the drug’s fat-blocking mechanism:

  • Oily spotting, oily stools, gas with discharge, fecal urgency, increased defecation, fecal incontinence (usually transient)

Aliduet Dosage and Administration

  • Oral administration
  • One capsule (120 mg orlistat / 600 mg L-carnitine) with each main meal (during or up to one hour after)

Aliduet Presentations

  • Boxes of 30, 60, and 90 capsules

What is Obesity?

According to the WHO, obesity is a chronic disease characterized by excessive body fat accumulation that impairs health.

Obesity’s Impact on Mexico

The 2006 National Health Survey reported that approximately 70% of the population over 20 is overweight or obese, with 30% meeting obesity criteria.

Etiology of Obesity

Obesity occurs when energy intake consistently exceeds expenditure, leading to excess calorie storage in adipose tissue.

Factors Causing Obesity

  1. Heredity
  2. Age
  3. Sex
  4. Environment and eating habits
  5. Lack of physical activity
  6. Pregnancy
  7. Childhood obesity
  8. Night eating syndrome
  9. Endocrine factors
  10. Drugs

Pediatric and Adolescent Obesity

Obesity before age 18 is predictive of adult obesity and associated with longer duration of obesity in adulthood.

Adult Obesity

Obesity after age 18 is characterized by cell hypertrophy and frequently associated with abdominovisceral obesity and metabolic complications.

Hypertrophic Obesity

Typical in adults, characterized by increased fat within adipocytes without an increase in cell number. Often associated with central fat distribution and relatively easier to treat.

Hyperplastic Obesity

A long-term form with increased adipocyte number and fat content. Individuals tend to be obese since childhood, with central and peripheral fat distribution, making treatment more challenging.

Body Mass Index (BMI)

BMI is calculated as weight (kg) divided by height squared (m²). Example: 70 kg / 1.75 m² = 22.9 kg/m².

Classification of Overweight and Obesity by BMI

  • Normal weight: 18.5-24.9 kg/m²
  • Overweight Grade I: 25-26.9 kg/m²
  • Overweight Grade II (Pre-obesity): 27-29.9 kg/m²
  • Obesity Grade I: 30-34.9 kg/m²
  • Obesity Grade II: 35-39.9 kg/m²
  • Obesity Grade III/IV: ≥ 40 kg/m² (Extreme Obesity)

Classification of Obesity by Distribution

  • Abdominovisceral (android, “apple”)
  • Gluteal-femoral (gynecoid, “pear”)

Waist-Hip Ratio

Calculated by dividing waist circumference (cm) by hip circumference (cm).

Abdominovisceral (Android) Obesity

Characterized by intra-abdominal fat accumulation in the stomach and chest, increasing the risk of obesity-related diseases.

Gluteal-Femoral (Gynecoid) Obesity

Characterized by fat accumulation in the hips, thighs, and buttocks, potentially leading to mechanical problems in extreme cases.

Excess Abdominal Fat

Waist circumference exceeding 90 cm in men and 84 cm in women indicates excess abdominal fat and increased health risks, even with normal BMI.

Overweight and Obesity in Children

40% of children in Mexico are overweight or obese due to changes in eating habits and physical activity levels, along with genetic factors.

Measuring Obesity in Children

BMI is a key parameter. Obesity is diagnosed when weight exceeds 20% over ideal weight for age, height, and sex.

Visceral Fat and Insulin Resistance

Excessive visceral fat increases free fatty acid flow into the bloodstream and liver, leading to elevated triglycerides, blood glucose, insulin, and insulin resistance in muscle.

Health Problems Associated with Obesity

  • Type 2 diabetes
  • Cardiovascular disease and hypertension
  • Respiratory diseases (sleep apnea)
  • Osteoarthritis
  • Psychological problems
  • Elevated LDL cholesterol
  • Elevated triglycerides
  • Reduced HDL cholesterol
  • Increased risk of certain cancers (endometrial, breast, prostate, colon)

Symptoms and Signs of Obesity

  • Sleep apnea
  • Increased cancer risk
  • Osteoarthritis
  • Skin disorders
  • Psychological disorders

Free Fatty Acids and Tissue Influence

Free fatty acids contribute to insulin resistance in skeletal muscle, liver, and endothelial cells, and impair insulin secretion by pancreatic β-cells.

Visceral Fat Cells vs. Other Fat Cells

Visceral fat cells release fatty acids into the bloodstream more readily, increasing glucose production in the liver and counteracting insulin action.

Fatty Acids and Insulin Activity

Fat cells produce hormones (e.g., tumor necrosis factor) that block insulin’s effects in other tissues. More fat cells and greater fat load lead to increased hormone production.

Inflammatory Process in Adipose Tissue

Inflammation in adipose tissue leads to the release of free fatty acids and adipokines, including inflammatory markers like C-reactive protein, IL-6, and TNF-α.