Understanding Obesity: Causes, Effects, and Treatment

Posted on Sep 26, 2024 in Medicine & Health

What is Obesity?

According to the World Health Organization (WHO), obesity is a chronic disease characterized by excessive accumulation of body fat to a level that impairs health.

Impact in Mexico

The 2006 National Health Survey of the Health Ministry reported:

  • About 70% of the population over age 20 are overweight or obese.
  • Of these, 30% meet the criteria for the diagnosis of obesity.

Etiology of Obesity

When energy intake exceeds expenditure, excess calories are deposited in adipose tissue. If this positive balance is maintained, obesity occurs. Therefore, there are two components to weight balance, and any anomalies of one (intake or expenditure) can lead to obesity. In a sense, the cause of obesity is simple: spending less energy than intake.

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

Types of Obesity

Pediatric and Adolescent Obesity

  • Onset before age 18.
  • Predictive of adult obesity.
  • Overweight children are more likely to be obese in adulthood.
  • Obese adults with a history of pediatric and adolescent obesity will suffer longer.

Adult Obesity

  • Post Top 18.
  • Cell hypertrophy predominates as a mechanism.
  • Most frequently associated with abdominovisceral obesity and its metabolic complications.

Hypertrophic Obesity

Hypertrophic obesity is typical of adults and is characterized by a large amount of fat in the adipocytes with no increase in the number of fat cells. These individuals tend to be thin or maintain their average weight to 30 or 40 years of age, at which point weight gain begins. This may be associated with an imbalance between caloric intake and use. Hypertrophic obese people usually have a central fat distribution; this problem tends to be more easily treated.

Hyperplastic Obesity

This corresponds to a long-term clinical form in which the number of adipocytes is increased and the amount of fat they contain. These individuals tend to be obese as children and have a significant weight gain during adolescence. After this age, the number of adipocytes is maintained throughout life. In this form of obesity, fat distribution is central and peripheral. The treatment is considerably more difficult.

Body Mass Index (BMI)

Calculating BMI

BMI is obtained by dividing weight in kilograms of a person between the square of their height in meters (kg/m2). For example, an adult weighing 70 kg and whose height is 1.75 m will have a BMI of 22.9 kg/m2.

Classification of Overweight and Obesity According to BMI

  • Normal weight: BMI between 18.5 and 24.9 kg/m2
  • Grade I overweight: BMI between 25 and 26.9 kg/m2
  • Grade II overweight (pre-obesity): BMI between 27 and 29.9 kg/m2
  • Grade I obesity: BMI between 30 and 34.9 kg/m2
  • Grade II obesity: BMI between 35 and 39.9 kg/m2
  • Obesity class III and IV: BMI ≥ 40 kg/m2 and extreme obesity

Classification of Obesity According to Fat Distribution

Fat Distribution: Apples and Pears

  • Abdominovisceral or visceroportal obesity
  • Gluteal-femoral or gynecoid obesity

Waist-Hip Ratio

The waist-hip ratio is calculated by dividing the measurement in centimeters from the waist between the hip measurement in centimeters.

WAIST SIZE IN CENTIMETERS / HIP SIZE IN CENTIMETERS

Abdominovisceral or Android Obesity

Those with an android fat distribution (often called an “apple”), which means that most of their body fat is intra-abdominal and accumulates in the stomach and chest, are supposed to be at greater risk of developing obesity-related diseases.

Gluteal-Femoral or Gynecoid Obesity

Commonly known as “pear”, which means that most body fat is accumulated in the hips, thighs and buttocks. It is assumed that mechanical problems may occur (joints, inner thighs) in extreme cases.

Excess Abdominal Fat

If the waist circumference exceeds 90 cm in men and 84 cm in women, it means that there is excess abdominal fat, which can pose a greater risk for health problems, even if your BMI is normal.

Overweight and Obesity in Children

Incidence and Factors

40% of children in Mexico are overweight or obese. This is due to the change of life that society has had, both in their eating habits and physical activity, which are important factors. These factors, together with the genetics of the Mexican population, influence the development of overweight.

Measuring Obesity in Children

One of the best parameters for assessing overweight or obesity is the body mass index. A child (6 to 19 years) is considered obese when their weight exceeds 20% over the ideal weight for their age, height, and sex.

Visceral Fat and Insulin Resistance

Influence of Visceral Fat

Excessive visceral fat results in a risk of cardiovascular disease. The main consequence is that there is an increase in the contribution of free fatty acids into the bloodstream and liver, resulting in an increase in triglycerides, blood glucose, and insulin. Moreover, these acids have toxic effects on the muscle and cause insulin resistance.

Health Problems Associated with Obesity and Overweight

  • Type 2 Diabetes
  • Cardiovascular disease and hypertension
  • Respiratory diseases (sleep apnea)
  • Osteoarthritis
  • Psychological problems
  • Raising the levels of LDL (“bad cholesterol”)
  • Elevated triglyceride levels
  • Reduced levels of HDL or “good cholesterol”
  • Increased risk of certain cancers, including endometrial cancer, breast cancer, prostate cancer, and colon cancer.

Symptoms and Signs of Obesity

  • Sleep apnea
  • Cancer
  • Osteoarthritis
  • Skin disorders
  • Psychological disorders

Influence of Free Fatty Acids on Tissues

Free fatty acids play an important role in the development of insulin resistance in skeletal muscle, liver, and endothelial cells, and the alteration of insulin secretion by pancreatic β cells.

Visceral Fat Cells vs. Other Fat Cells

Abdominal fat cells more easily send fatty acids into the bloodstream. These fatty acids flow directly from the abdominal tissues to the liver and increase the production of glucose from the liver. It is easy to understand how abdominal fat might counteract the action of insulin in the liver and increase glucose production.

How Fatty Acids Alter Insulin Activity

Fat cells produce hormones that go into the bloodstream. At least two of these hormones (tumor necrosis factor) are able to block the effect of insulin in other tissues. The more fat cells there are, and the greater their fat load, the more of these hormones are produced.

Inflammatory Process in Adipose Tissue

Initially, inflammation increases in adipose tissue, and as a result, there is a discharge of free fatty acids and adipokines.

Markers of Inflammation

  • C-reactive protein
  • Interleukin 6 (IL-6)
  • Tumor necrosis factor alpha (TNF-α)

What Happens if You Lose 10 kg of Weight?

  • 15% decrease in LDL cholesterol levels
  • 8% increase in HDL cholesterol
  • Blood pressure decrease (typically, for every 1% reduction in weight, blood pressure decreases 1-2mm Hg)
  • Greater benefits if accompanied by exercise

Objectives in the Treatment of Obesity

  • Modest weight loss (10% or maybe even 5% of body weight) is enough to control, or at least improve, the majority of the complications of obesity.
  • Maintaining the new weight and reaching the best possible weight in the context of overall health.

Options for the Treatment and Control of Obesity

  • Loss of 10% of excess weight provides beneficial effects on health.
  • Diet and exercise programs
  • Changes in behavior and lifestyle
  • Medical treatment
  • Surgical treatment

Drugs Used in the Treatment of Obesity

Classification by Mechanism of Action

  1. Drugs that reduce power consumption (appetite)
    • Noradrenergic agents
    • Serotonergic agents
  2. Drugs that decrease the absorption of nutrients
    • Orlistat (Xenical)
  3. Drugs that increase energy expenditure
    • Ephedrine and xanthines such as caffeine, theophylline, and thyroid hormone
  4. Drugs that reduce the size of fat cells and transform fat molecules into energy through the oxidation of fatty acids

Surgical Treatment for Obesity

In people with morbid obesity (BMI> 40) and in those with less severe obesity and serious complications or life-threatening conditions, where treatments based on diet, exercise, and medications are ineffective in the long term, surgical procedures are the treatment of choice. These procedures can result in great loss of weight that usually remains well for > 5 years. The only long-term effective treatment for these patients is surgery.

Fat Absorption

Role of Lipases

For fat absorption to be possible, lipases must convert triglycerides to fatty acids.

Lipolytic Enzymes

Humans have four lipolytic enzymes involved in the sequential enzymatic digestion of lipids:

  • Gastric lipase
  • Pancreatic lipase
  • Lipase carboxylester
  • Phospholipase A2

Pancreatic lipase is by far the most important digestive lipase.

Orlistat

What is Orlistat?

Orlistat is a drug that was approved in early 1999 by the FDA (Food and Drug Administration) for use in weight reduction treatments.

Orlistat, also known as tetrahidrolipostatina, is a drug to treat obesity. Its main function is to prevent the absorption of fat in the human diet, thereby reducing caloric intake.

Mechanism of Action

Orlistat is a potent, specific, irreversible, and long-acting inhibitor of gastrointestinal lipases. It exerts its therapeutic effect in the stomach and in the lumen of the small intestine. Orlistat blocks the action of lipase and thus prevents the conversion of triglycerides to fatty acids. This results in a 30% reduction in systemic absorption of fats contained in a diet that has a normal fat percentage (30% of total calories).

Systemic Absorption of Orlistat

In general, after long-term treatment with therapeutic doses, detection of unchanged Orlistat in plasma was sporadic, and concentrations were extremely low (<10 ng/mL) with no evidence of accumulation, which is consistent with negligible systemic absorption.

Elimination of Orlistat

The major route of elimination of unabsorbed drug is fecal excretion.

  • 97% is excreted in the feces
  • 83% as unchanged orlistat

Renal excretion was <2% of the administered dose.

Fat Excretion with Orlistat

Studies in healthy volunteers showed that the percentage of fecal fat excretion was dose-dependent but reached a maximum of 30% of excretion with 360 mg/day of the drug. Higher doses did not produce a significant increase in the percentage of fat excreted in feces.

Weight Loss with Orlistat vs. Diet Only

Weight loss of 10% or more was achieved in 60% of patients who used orlistat and only 33% of patients with an exclusive diet.

Orlistat in Adolescents

Importance of Early Management of Obesity

Excess weight in adolescents eventually brings health effects, notably increased risk of high blood pressure, high cholesterol, and the development of type 2 diabetes. Obesity in children and adolescents is closely linked with early mortality in adults.

FDA Approval

For the first time in December 2003, the Food and Drug Administration (FDA) in the U.S. approved the use of a prescription drug for weight loss, orlistat, in adolescents 12 to 16 years.

Orlistat and Glucose Metabolism

Obesity and Type 2 Diabetes

Obesity is the most important modifiable risk factor in the pathogenesis of type 2 diabetes mellitus. UKPDS26 data show that a 1% decrease in glycosylated hemoglobin (HbA1c) is associated with:

  • 35% reduction in microvascular complications
  • 18% decrease in the incidence of myocardial infarction
  • Decrease of 25% of deaths related to diabetes

Orlistat in Preventing Diabetes Mellitus

In 2004, the XENDOS study showed that orlistat, along with changes in lifestyle, provided a lower risk of developing type 2 diabetes by 37%, according to the evaluation of all patients.

Other Factors in Glycemic Control

At least two other effects of orlistat may explain its action against hyperglycemia:

  • Decreased circulating free fatty acids
  • Enhancing incretin secretion of the digestive tract, in particular peptide 1, similar to glucagon (GLP-1, glucagon-like peptide-1)

Orlistat in Diabetic Patients

Effects Beyond Weight Reduction

Orlistat also improves other cardiovascular risk parameters: fasting blood glucose decreased significantly when orlistat was added to changing lifestyles, and the same happened with HbA1c.

Orlistat and Blood Pressure

Modest reductions in weight lead to improvement in blood pressure in obese individuals, which is even greater if accompanied by exercise. Also, weight loss in obese individuals with hypertension can reduce the need for antihypertensive medication.

Orlistat and Markers of Inflammation

Effects on Inflammation

Studies have shown a reduction of cytokine levels after weight loss and increased TNF-α decreased in the group treated with orlistat. Other studies have shown:

  • Decreased C-reactive protein
  • Greater decrease in the values of leptin and increased adiponectin

Orlistat and Postprandial Lipemia

Effects on Postprandial Lipemia

Orlistat, by blocking lipase and hindering the absorption of 30% of dietary fat, reduces postprandial hyperlipidemia. In addition, by interfering with the formation of micelles, orlistat interferes indirectly with the absorption of cholesterol, since the micelles are necessary to bring the cholesterol molecules to the surface of enterocytes.

Studies have noted that obese patients treated with orlistat had a significant decrease in levels of total cholesterol and LDL cholesterol.

Orlistat and Waist Circumference

Effects on Abdominal Fat

The reduced flow of lipids and fatty acids from the intestine has been associated with a reduction of visceral fat by 44% higher than appreciated for the same weight loss without orlistat.

L-Carnitine

What is L-Carnitine?

L-Carnitine is an amino acid derivative, is low molecular weight, and is a cofactor in the metabolism of fatty acids. L-carnitine is synthesized by the body from 2 amino acids (methionine and lysine).

Mechanism of Action

With L-Carnitine, free fatty acids are transported into the mitochondria of cells. Within fat chains involved in the metabolic process called beta-oxidation of fat, the chains are broken and transformed into groups receiving the name Acetyl CoA. These groups then enter the process called the Krebs cycle, where the result is ATP (energy).

Benefits of L-Carnitine Supplementation

Exogenous carnitine increases systemic and hepatic carnitine. This can lead to increased utilization of free fatty acids, thereby increasing the available energy flow, preserving muscle protein while fasting or exercising vigorously.

L-Carnitine and Weight Control

Taking supplements can help achieve optimal fat oxidation and thus promote a healthy body weight. Thus, L-carnitine supplements may help support weight loss programs that include calorie reduction and exercise.

L-Carnitine and Exercise

Benefits of L-Carnitine on Exercise

  • Improve exercise capacity and oxygen consumption
  • Reduce fatigue
  • Improve muscle conditioning

L-Carnitine and Cardiovascular Health

L-Carnitine is one of the most important nutrients and safer to maintain cardiovascular health. The human heart gets about 70% of the energy used in the breakdown of fats. Clinical data indicate that L-carnitine supplements may benefit muscle and healthy heartbeat and increase the viability of heart muscle.

Aliduet

Pharmaceutical Form and Formulation

60 mg Capsule

Each capsule contains:

  • Orlistat … … … … … … … … … … … … … 60 mg
  • L-Carnitine Tartrate … … … … …. … 600 mg
  • Excipient cbp … … … … … … … … … .. 1 capsule

120 mg Capsule

Each capsule contains:

  • Orlistat … … … … … … … … … … … … … 120 mg
  • L-Carnitine Tartrate … … … … …. … 600 mg
  • Excipient cbp … … … … … … … … … .. 1 capsule

Therapeutic Indications

Aliduet, in conjunction with a hypocaloric diet plan for obese or overweight patients, including those with risk factors associated with obesity, enables effective long-term control of weight (reducing, maintenance, and prevention of weight gain). It is also indicated to improve risk factors and conditions associated with obesity, such as hypercholesterolemia, glucose intolerance, type 2 diabetes, hypertension, hyperinsulinemia, and visceral fat reduction.

Contraindications

Aliduet is contraindicated in patients with:

  • Chronic malabsorption syndrome
  • Known hypersensitivity to any component of the formula

Precautions

  • May increase the possibility of experiencing gastrointestinal events when Orlistat/Carnitine is administered with a diet high in fat. Daily fat intake should be distributed over three main meals.
  • In type 2 diabetes, may allow or require reduction in dosage of oral hypoglycemic medication (e.g., sulfonylureas)
  • There has been a reduction in cyclosporine plasma levels with coadministration of Orlistat/Carnitine
  • Orlistat showed a 25-30% reduction in systemic exposure to amiodarone and desetilamiodarona

Side Effects and Adverse Reactions

Side effects are mainly gastrointestinal in nature and are related to the pharmacological effect that prevents the absorption of dietary fat.

Commonly observed side effects include oily spotting, oily or fatty stools, gas with fecal discharge, fecal urgency, oily evacuation, increased defecation, and fecal incontinence.

These gastrointestinal adverse events were generally transient.

Dosage and Route of Administration

  • Route of Administration: Oral
  • Standard adult dosage: The recommended dose of orlistat 120 mg/Carnitine 600 mg capsule is one with each main meal (during or up to one hour after the meal).
  • If you omit any foods containing fat, taking the corresponding dose is not necessary.

Presentations

Aliduet is available in boxes of 30, 60, and 90 capsules.