Polygenic score
Influential genes: FTO,MC4R, BDNF
The FTO gene has an established association with obesity. In particular, certain alterations in this gene have been observed to affect fluctuations in body mass index (BMI) and predisposition to obesity.
Mutations in the MC4R gene are the most common monogenic cause of severe obesity. The MC4R receptor plays a role in regulating appetite and energy balance.
BDNF is involved in the regulation of appetite and food intake. Variants in the BDNF gene have been associated with obesity and increased food consumption.
Obesity is an abnormal or excessive fat accumulation in the body that may impair health, caused by the consumption of more calories than being burnt by the basal metabolism, thermic effect of food, and physical activity. It is defined by a BMI of 30 or more and therefore differentiated from overweight covering BMI specter of 25-29,9. Besides obvious physical changes, obesity can have severe impact on human health, including coronary heart disease, type 2 diabetes, stroke, non-alcoholic fatty liver disease potentially leading to liver cirrhosis, obstructive sleep apnea, various fungal infections, fertility problems, or even many types of cancer. The patient’s life comfort is reduced due to breathlessness, increased sweating, snoring, joint and back pain, psychological problems, and many others. The combination with other medical conditions (such as abdominal obesity, insulin resistance, elevated blood pressure, or irregular blood lipid levels) is called “Metabolic syndrome”, significantly increasing a patient’s risk for cardiovascular disease and type 2 diabetes mellitus.
Due to the modern lifestyle full of stress, unhealthy diets, and insufficient physical activity, the obesity rate worldwide is quickly rising and turning into a pandemic of obesity, which is now recognized as one of the most important public health threats. According to the World Health Organization, more than 650 million adults suffered from obesity in 2016. The worldwide prevalence nearly tripled between 1975 and 2016. The prevalence is also rising among children – in 2016 more than 124 million children and adolescents were obese (6% of girls, 8% of boys). [1]
There are many risk factors contributing to the development of obesity – both modifiable and non-modifiable. Alongside well-known risk factors, such as an unhealthy diet and a lack of physical activity, there is stress, mental problems leading to overeating, or sleep deprivation. The environment has a huge impact on a person's lifestyle (low socioeconomic status, easy access to unhealthy fast foods, limited possibilities for physical activity, or a shortage of time due to various reasons). Other diseases, such as hypothyroidism or polycystic ovaries syndrome, also increase the risk.
Obesity is a complex disease influenced by both genetic and environmental factors. Genes play a role in determining susceptibility to obesity, but they are not the only cause. Researchers have already mapped specific genetic pathways and variants associated with obesity.
Genome-wide association studies (GWAS) have identified several genetic variants associated with obesity. These genes are involved in appetite regulation, energy metabolism, and fat storage. In particular, the FTO gene has been shown to be strongly associated with obesity. Other genes involved in leptin signaling, insulin signaling, and adipogenesis have also been investigated.[2]
In addition, genetic studies, including rare variant analysis, functional genomics, and epigenetics, provide even deeper insights into the mechanisms. For example, rare genetic variants affecting the MC4R gene have been associated with severe obesity phenotypes. Epigenetic modifications, which affect gene expression without altering the DNA sequence, are also being studied as potential drivers of obesity susceptibility.[6,7]
Genetic testing allows us to determine if you have a predisposition to develop this disease. At Macromo, we use evidence-based polygenic risk scores and causal genetic variants to assess the genetic risk. The polygenic risk score (PRS) represents the total number of genetic variants that increase an individual's risk of developing a particular disease. All the variants in his or her entire genome are summed and ranked according to their effect on disease development.
Many complications are linked to the most obvious symptom – weight gain. Patients suffer from difficulty breathing while sleeping (also known as sleep apnea), back and/or joint pain, problems with thermoregulation, infections in skin folds, depression, shortness of breath, or excessive sweating. The specter of complications is broad and it's important to realize how many conditions can be influenced by our weight.
The most basic tool for diagnosing obesity, supported by a thorough history of the patient's lifestyle, is the calculation of BMI. This is a very simple formula using the patient's weight and height.
BMI is interpreted using standard categories, valid for adults over 20. [3]
It’s important to realize that BMI is highly influenced by the weight of the individual, not considering muscles being heavier than fat. Therefore, it’s optimal to use additive diagnostics methods.
The waist circumference is used in diagnostics of abdominal obesity (a condition with excessive buildup of abdominal fat, that is highly dangerous due to its hormonal activity), the values for substantially increased risk are defined as ≥88 cm for women and ≥102 cm for men. It’s also possible to assess the risk using the waist-to-hip ratio (=waist circumference/hip circumference). Values defining obesity are >0,85 for women and >0,9 for men.[5]
For a general measure of body fat percentage, it’s possible to use a device called a caliper, to measure differently located skinfolds in millimeters. Bioimpedance measurements (using an electric current to determine the body's fat content) or a dual-energy X-ray absorptiometry (DEXA) scan can give you even more detailed information about your body's composition.
The best way to treat obesity is to introduce changes to your lifestyle such as a balanced diet and regular exercise. Finding a nutritional specialist can be very beneficial in forming the right diet. If lifestyle changes alone aren’t sufficient, a doctor can in extreme cases indicate few pharmacotherapy possibilities such as:
· Inhibitors of pancreatic lipase (Orlistat) - decreases the lipid absorption in the gastrointestinal tract
· Anorectics (phentermine – Adipex retard, bupropion/naltrexone – Mysimba) - influences food intake centrum in the brain and reduces appetite
· GLP – 1 analog (liraglutide – Saxenda) – increases the secretion of insulin, slows gastric emptying, and reduces food intake
As a last resort, indicated only for people with BMI ≥ 35 kg/m2 AND comorbidities (such as diabetes or metabolic syndrome), or ≥ 40 kg/m2 without comorbidities, bariatric surgery can be performed. It’s a weight-loss surgery with the 3 most common types being:
· Gastric band – reduces stomach size, making the patient feel full sooner (the only reversible surgery)
· Gastric bypass – connecting the upper part of the stomach directly with the small intestine, decreasing the calories income from digested food
· Sleeve gastrectomy – separating a part of the stomach, which can’t hold as much food
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All forms of bariatric surgery are major procedures and pose serious risks. For the long-term effect of the surgery, it’s important to maintain lifestyle changes.
The positive aspect of obesity is that most of the causes are modifiable and lifestyle changes can dramatically lower the risks for overweight and obesity. There are a few basic rules when it comes to eating habits – you should eat only as many calories as you use, avoid saturated and trans fats, and foods high in added sugars. Substituting simple carbs with complex carbs and eradicating prefabricated sugars can greatly improve your health. All those principles combined with any physical activity can already significantly stabilize a patient's weight and prevent the development of obesity and its related complications.
Obesity is without doubt linked to a high risk of all-cause mortality. Some studies have concluded a phenomenon called “the obesity paradox” – a state in which patients with higher BMIs can be protected from a few health conditions. However, these studies haven’t taken into account body mass type and body fat distribution. It’s important to look at obesity as a whole and use various diagnostics methods as already mentioned above. If the patient manages to stabilize their weight and total body fat, and increases their physical activity level, the prognosis is favorable. If left untreated, obesity brings a lot of health risks that can have a fatal impact resulting in heart attack, liver cirrhosis and liver failure, obstructive sleep apnea, and general infections.
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