33. Consequences of obesity. Therapeutic possibilities

Consequences of obesity

Obesity is associated with a clear and substantial increase in both morbidity and mortality. A recent study found that men within a healthy weight range lived about six years longer than men who were morbidly obese. This may not sound like much; however this does not show how the quality of life is decreased during the last living years of obese people. Obesity is estimated to increase cardiovascular mortality 4-fold and cancer mortality 2-fold. Which pathophysiological changes underly this increased mortality?

Cardiovascular: A larger body mass means that there are more tissues for the heart to supply blood to. This increases cardiac output. Obesity is associated with diabetes type 2, which causes hyperinsulinaemia. High levels of insulin increase salt and water reabsorption in the kidney, which increases plasma volume and therefore causes hypertension. Both hyperinsulinaemia and high body mass increases sympathetic activity, which also causes hypertension.

Hyperlipidaemia increases the risk for atherosclerosis and coronary artery disease. Hypertension, high CO and coronary artery disease increases the risk for heart failure. The venous congestion in heart failure predisposes to venous thrombosis.

Respiratory: Thicker, less compliant chest wall causes an increase in work of breathing, potentially causing Pickwick syndrome. Sleep apnoea syndrome occurs more frequently in obese people. Both these syndromes can cause pulmonary hypertension and respiratory failure.

Metabolic: Diabetes mellitus type 2 develops more frequently in obese. Hyperlipidaemia. Increased risk for gout.

Gastrointestinal: Non-alcoholic fatty liver disease. Gallstones may develop due to increased hepatic cholesterol secretion.

Renal: Chronic renal failure may develop due to hypertension, diabetes and hyperlipidaemia.

Musculoskeletal: Large loads on the knees and hips can cause arthrosis.

Endocrine: It mustn’t be forgotten that adipose tissue has functions as an endocrine organ. Adipose tissue secretes oestrogen and prolactin, which may increase the incidence of certain breast and endometrial tumors.

Inflammatory: Excess of fat in adipose tissues stimulates them to release inflammatory mediators like TNF and IL-6. It’s known nowadays that obesity causes low-grade chronic inflammation. This inflammation may contribute to insulin resistance and the development of other chronic inflammatory conditions in obese people.

Haematic: Plasminogen activator inhibitor 1 (PAI-1) is a physiological inhibitor of plasminogen activators. This protein is elevated in obese people, which may increase the tendency for thrombosis.

Psychological: Psychological issues can not only foreshadow development of obesity but follow its development. Society views obesity very negatively and tends to believe that obese people are “weak-willed”. Obese people may internalize these views, which may affect their self-worth. Depression and integration disorders may follow.

Difficulties in treating obesity

The treatment of obesity is complicated. Anyone who has tried to lose weight can tell you that maintaining a lower body weight is very hard. Regaining weight after weight loss often occurs. Studies of participants in weight-loss TV programs like “The biggest loser” has shown that most participants regain most of their lost weight after 6 years.

Recent research shows that the bodies of obese people who lose weight decrease the metabolic rate to try to conserve the energy these people are trying so hard to lose. The brain is not evolutionarily adapted to prevent obesity, so brains of obese people are satisfied that the body has such huge spare energy stores. When these people lose weight their adipose tissue produces less leptin, which, together with other hormones, makes the brain think that they’re starving. The brain influences the body’s tissues to be more energy-conservative, which decreases the metabolic rate.

The previously mentioned “Biggest loser” study showed that the contestants lost around 58 kg each right after the competition. Their resting metabolic rate also dropped by around 610 calories per day at the same time. 6 years later however, they gained back an average of 40 kg each, but the resting metabolic rate stayed the same. So they regained most of the weight, but their metabolic rate was now much lower than it was before the competition!

In addition to the fact that the body decreases the metabolic as you’re dieting is the fact that the hypothalamus makes you more aware of all the food you’re not eating and increases the pleasure (palatability) you feel if you do cave in to the urge to binge-eat.

Sources:

https://www.nejm.org/doi/full/10.1056/NEJM199503093321001#t=article

https://www.physiology.org/doi/pdf/10.1152/ajpregu.00755.2010

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693571/

https://onlinelibrary.wiley.com/doi/full/10.1002/oby.21538

https://www.youtube.com/watch?v=orh1W0sxCQI

Treatment options in obesity

As with all chronic medical conditions must the treatment of obesity begin with a partnership of a highly motivated patients and a committed team of health professionals. This team may include a physician, a psychologist or psychiatrist, exercise therapists, dietitians and others. The patient and family must be informed and prepared for the importance and difficulties of the therapy. Weight loss must be monitored by professionals to prevent electrolyte derangements and other adverse effects from developing.

The treatment itself should consist of restriction of calorie intake and increased physical activity. The diet should consist of enough dietary protein (to prevent protein catabolism) and essential nutrients. Processed foods and foods high in fat and sugar should be restricted.

Pharmacological therapy exists but should be reserved for those who can’t reach sufficient target weight without it. These drugs may have significant side effects, and their efficacy is questionable. Orlistat is a pancreas lipase inhibitor, which inhibits the digestion and therefore the absorption of fats in the food. Antidepressant therapy like bupropion-naltrexone may aid weight loss.

These drugs are not important for the exam.

Bariatric surgery is an umbrella term for surgeries that aim to induce weight loss. These surgeries achieve this goal by reducing the size of the stomach, which causes the patient to feel full earlier when eating. This treatment is mostly reserved for patients with BMI above 30 that also have comorbidities.


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32. Etiology and pathogenesis of obesity

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34. Metabolic syndrome

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