Obesity – The 21st Century Pandemic

Obesity is a chronic disease characterized by excessive accumulation of fat in the body. It causes disruptions in bodily functions and metabolic processes, decreases quality of life, increases the prevalence of many diseases, and shortens lifespan. It is a significant health and socioeconomic problem, as it ranks just behind smoking among the risk factors for cardiovascular diseases, which are the leading cause of death in modern civilization.

How Common is Obesity?

In Europe, about 55% of adults aged 25 to 64 years are overweight, and 15% are obese, meaning 69% of them have excessive body weight (CINDI 2004). Obesity is a risk factor for cardiovascular diseases and increases the prevalence of arterial hypertension. It is also associated with a higher incidence of certain types of cancer, gallstones, respiratory disorders, osteoarthritis of the large joints, cardiac hypertrophy, and heart failure. In 2008, 1.5 billion adults were reported to be overweight, and in 2013, the American Health Organization declared obesity a disease.

Pathophysiological Background of Obesity

Adipogenesis refers to the differentiation of preadipocytes into mature adipocytes, which are capable of storing excess consumed energy as fat. Small adipocytes in lean individuals maintain metabolic homeostasis; however, large adipocytes in obese individuals recruit macrophages from circulation, promote inflammation, and secrete several factors that cause insulin resistance and atherogenesis. Adipose tissue is not only a passive reservoir of excess energy but is also the largest endocrine organ. It responds to afferent stimuli from the central nervous system and classical endocrine glands, as it has appropriate hormonal receptors, and produces and secretes substances with endocrine, paracrine, and autocrine effects. Adipocytes secrete hormones and hormone-like substances known as adipocytokines (such as leptin, IL-1, IL-6…), which actively participate in the regulation of appetite, energy expenditure, tissue sensitivity to insulin, the immune system, stress response, sexual maturation, and reproduction. Adipocytes also have various receptors involved in regulatory loops (insulin receptors, sex hormone receptors, etc.). They also produce enzymes that influence lipid metabolism, the renin-angiotensin-aldosterone system, glucocorticoid metabolism, and more. Abdominal (visceral) fat differs from subcutaneous peripheral fat, which predominates in the gynoid type of obesity, in its metabolic characteristics: it consists of large adipocytes that are insulin-resistant and have many beta 1 and beta 2 adrenergic receptors, more angiotensin 1 receptors, and glucocorticoid receptors. Metabolically, they are highly active, releasing many free fatty acids (FFAs) and cytokines (e.g., TNF-alpha, IL-6), which cause insulin resistance in muscle tissue and the liver. What Influences Obesity?

Genetics: Nutritional status in people under normal living conditions is more than 60% genetically determined. More than 250 genetic markers that affect variables used to define nutritional status, such as body mass index, skinfold thickness, waist circumference, and body fat percentage, have already been discovered. In normal cases, only a predisposition to obesity is inherited, while environmental factors determine whether obesity will develop. Exceptions are rare cases of extreme obesity occurring in early childhood, which involve mutations in genes for proteins. Environmental Influences: These are manifested in dietary habits, ingrained patterns of physical activity, and significant roles of unawareness and lower socioeconomic status in the development of obesity. Psychological Factors: Conditions of chronic stress lead to overeating and obesity. Obesity is more common with certain mental illnesses and due to medications (some neuroleptics) that increase appetite, alter metabolism, and reduce energy expenditure. As a result, a significant number of psychotic patients develop metabolic syndrome with insulin resistance and type 2 diabetes after only a few months of treatment. Critical Periods for Obesity: Children born with low birth weight are more likely to develop obesity and insulin resistance later in life. Children who are breastfed have a lower risk of obesity in adulthood. If a child is obese between the ages of five and ten and has at least one obese parent, the obesity will develop as progressive obesity with an increased number of fat cells in adulthood, which is very difficult to treat. Women are more likely to gain weight after puberty, during pregnancy or after childbirth, some while taking hormonal contraceptives, and very often after menopause, when fat accumulates centrally. Hormonal Disorders: Very rare as a primary cause of obesity, but more often a consequence. After injury, tumors, or surgery in the area of the base of the skull, which damage the centers for hunger and satiety, hypothalamic obesity can develop, which is difficult to treat. Central obesity and muscle atrophy as a result of excessive cortisol activity are associated with Cushing’s syndrome. Hypothyroidism reduces metabolism and energy expenditure, potentially increasing body weight by several kilograms. In women with polycystic ovary syndrome, central obesity is present in 50%. Inhibited lipolysis due to growth hormone deficiency causes excessive accumulation of visceral fat in patients with hypopituitarism. Smoking Cessation: As a consequence of nicotine withdrawal, body weight usually increases by a few kilograms.

Diagnosis of Obesity

When treating patients with obesity, the following factors are important: family history, onset of obesity, previous weight loss attempts, comorbidities, and their treatment. We weigh the patient, measure their height, and measure waist and hip circumference. Laboratory indicators, especially fasting glucose, and a lipid profile are assessed. Nutritional status is expressed by body mass index (BMI), which shows a good correlation with the amount of body fat but does not provide information about fat distribution. Depending on the distribution of body fat, we distinguish between gynoid, peripheral or “pear-shaped” obesity, where fat accumulates in the subcutaneous tissue, and android or central obesity, where visceral fat accumulates in the abdomen and chest around internal organs. The first type often leads to complications due to mechanical strain (e.g., osteoarthritis, varicose veins, edema, cellulite, gallstones). Central obesity is associated with metabolic disorders, causing insulin resistance, which progresses to impaired glucose tolerance and type 2 diabetes, arterial hypertension, and cardiovascular diseases. Both types can be visually differentiated, and the objective indicator is waist circumference. Waist circumference indicates whether the patient has increased amounts of fat in the abdominal area (visceral, abdominal fat) and, consequently, an increased risk of developing type 2 diabetes and cardiovascular complications. In cases of morbid obesity with a BMI of 40 or more, there is a huge amount of accumulated fat both in the abdomen and peripherally, and the risk for all obesity-related diseases is extremely high.

Metabolic Syndrome

In patients with metabolic syndrome, the processes of atherogenesis are accelerated, significantly increasing the risk of cardiovascular diseases and mortality. It is present when a person has three of the following factors:

• Waist circumference: Men ≥ 94 cm (>102 cm indicates a very high risk), Women ≥ 80 cm (>88 cm indicates a very high risk),
• Plasma triglycerides: ≥ 1.7 mmol/L or if the person is already on certain medications
• Reduced HDL cholesterol: Men 1.0 mmol/L, Women 1.3 mmol/L or if the person is already on certain medications
• Systolic blood pressure: ≥ 130 mmHg or diastolic blood pressure > 85 mmHg or if the person is already on certain medications
• Fasting plasma glucose: ≥ 5.6 mmol/L or if the person is already on antihyperglycemic medications

Diseases and Complications Associated with Obesity

Cardiovascular Diseases	Gastrointestinal Diseases	Respiratory Diseases
Coronary artery disease, arterial hypertension, stroke, DVT, lymphedema, heart failure	Hiatal hernia with reflux disease, gallstones, colorectal cancer, golden staph infection, liver steatosis	Restrictive ventilatory disorder, primary alveolar hypoventilation, obstructive sleep apnea, dyspnea
Metabolic Disorders	Musculoskeletal Disorders	Urinary Tract and Reproductive Disorders
Insulin resistance, type 2 diabetes, dyslipidemia (low HDL, elevated triglycerides), polycystic ovary syndrome	Degenerative osteoarthritis, flat feet	Stress incontinence, reduced fertility, pregnancy complications
Breast Diseases	Skin	Mental Disorders
Breast cancer, gynecomastia	Intertrigo, cellulite	Anxiety, depression, low self-esteem

Treatment of Obesity

The type of treatment depends on BMI. For individuals with a BMI over 25 kg/m², diet and exercise are recommended. Pharmacotherapy is initiated for those with a BMI of 27 or higher if the patient has associated health issues (hypertension, dyslipidemia, type 2 diabetes) or a BMI over 30. Bariatric surgery is indicated for patients with a BMI over 35 who are at risk due to other health conditions or a BMI over 40.

Non-Pharmacological Treatment

Lifestyle Change: Cognitive-behavioral therapy helps identify and eliminate faulty patterns that have led to weight gain, and supports the patient in developing new habits for weight loss and maintenance. Continuous support and counseling are needed during weight loss and maintenance, and this is the responsibility of the primary care physician who regularly monitors the patient. Dietary Advice: A healthy, mixed diet with lower fat and less concentrated carbohydrates, rich in fiber, divided into 4-5 meals per day, and adequate intake of non-caloric fluids. Daily caloric intake should be 500-700 calories less than the patient’s needs, roughly calculated by multiplying body weight in kilograms by 25 calories. After the first two weeks of weight loss, the rate of weight loss slows, with optimal weight loss of two to three kg per month. Regular Physical Activity: The minimum goal is 30-60 minutes, 5-7 times per week, planned individually and adhering to principles of gradual progression. Aerobic exercises (walking, running, swimming, cycling) are recommended and should be moderate activities (increasing heart rate to 100/140 beats per minute, depending on age and health condition). Increasing physical activity and developing movement habits are advised as essential for long-term weight maintenance.

Pharmacological Treatment

Orlistat: The first medication is orlistat, an intestinal lipase inhibitor. It acts in the intestines to inhibit fat digestion, preventing fat absorption and resulting in its excretion in the stool. Patients take the medication three times a day before meals. If patients do not adhere to dietary fat reduction instructions, they may experience digestive issues. Side effects include liver dysfunction and gastrointestinal problems, and attention should be paid to impaired absorption of fat-soluble vitamins (A, D, E, K), beta-carotene, and some medications. Other Approved Medications in the U.S.: Lorcaserin, liraglutide, and a combination of topiramate and phentermine. However, many medications with reduced side effects are still under investigation. These aim at endogenous endocrine transmitters regulating homeostasis and metabolism. The discovery of molecular mechanisms regulating adipocyte metabolism suggests that modulating cGMP signaling could create new targets against obesity. Lorcaserin: Classified as a benzodiazepine, it may have negative effects on the heart and blood vessels. It is a selective agonist of serotonin 5HT receptors; activation of these receptors leads to activation of POMC, indirectly reducing body weight due to feelings of fullness and decreased appetite. The FDA approved it for use in 2012. Topiramate and Phentermine Combination: Both active ingredients reportedly reduce appetite and food cravings. It is contraindicated in pregnant women and not approved for long-term use. Liraglutide: This drug is used for treating diabetes. It is an analog of glucagon-like peptide 1 (GLP-1), which binds to and activates the GLP-1 receptor. Natural GLP-1 is an endogenous incretin hormone that increases insulin secretion from pancreatic beta cells in a glucose-dependent manner. Liraglutide promotes insulin secretion and reduces inappropriate glucagon secretion relative to blood glucose levels. It reduces body weight through mechanisms that include decreased hunger and reduced food intake. GLP-1 is a physiological regulator of appetite and food intake, and the drug acts on brain regions involved in appetite regulation, enhancing satiety signals and reducing hunger signals.

Surgical Treatment of Obesity

Indications for Surgical Treatment: BMI>40, BMI>35 with associated health risks Repeated failure of non-surgical treatments Motivated patient If a patient, despite numerous attempts, fails to lose weight and their health and life are threatened by obesity, a surgical procedure to reduce stomach volume or the surface area of the small intestine through bypass surgery is indicated. Reducing the stomach to 50 ml limits the intake of large amounts of food, while bypassing a significant portion of the intestine from the functional digestive tract causes malabsorption. Surgeries are categorized as restrictive surgeries, malabsorptive surgeries, or a combination of both. Each can be performed laparoscopically or through an open incision. The laparoscopic Roux-en-Y gastric bypass is recommended as it has shown the best long-term results. This surgery involves a restrictive surgical procedure and a short gastroduodenal bypass. Patients typically do not experience issues with protein malabsorption, and it has been proven to reduce hunger. Complications: Perioperative mortality <1%, occurrence of infection, pulmonary embolism, wound dehiscence, stenosis. Contraindications for surgery include pulmonary diseases, unstable cardiovascular diseases, blood clotting disorders, and portal hypertension.

Prognosis

Obesity is a chronic disease that has reached such proportions that it can be described as a pandemic. When assessing the degree of obesity, both indicators, BMI and waist circumference, must be considered, as both are associated with increased mortality. Ectopic lipid accumulation in the liver, muscles, and pancreas, associated with central obesity, causes lipotoxic damage to these and other organs. The harmful effects of obesity are referred to as adipotoxicity. Treatment of obesity and metabolic syndrome is long-term, involving a weight loss phase followed by a much longer and more demanding phase of maintaining the achieved body weight. Success is only possible if the patient changes their lifestyle, with regular exercise having exceptionally beneficial effects. Successful moderate weight loss reduces the incidence of type 2 diabetes, cardiovascular risk factors, and mortality. It is also important for the patient to experience improved quality of life.

Conclusion

The condition where the human body uses its own fat cells as a source of fuel and energy is called ketosis. Ketosis and the subsequent reduction in insulin levels are major reasons why low-carbohydrate diets are effective for weight loss. Diabetic ketoacidosis can occur due to a lack of insulin effects. Ketoacidosis is significantly accelerated in type 1 diabetes due to a lack of insulin in the blood. The body tries to alleviate acidosis by increasing carbon dioxide excretion, which is why patients experience deep breathing as a symptom.
Article sourced from Najzdravnik.comhttps://najzdravnik.com/blogs/blog/debelost-pandemija-21-stoletja