The Definition and Prevalence of Obesity and Metabolic Syndrome: Correlative Clinical Evaluation Based on Phenotypes

Increase in the prevalence of obesity has become a major worldwide health problem in adults as well as among children and adolescents. In the last four decades, studies have revealed that the significant increase in the prevalence of obesity has become a pandemic. Obesity is the result of complex interactions between biological, genetic, environmental, and behavioral factors. Indeed, almost all of the children suffering from obesity in early childhood face with being overweight or obese in adolescence. Different phenotypes have different risk factors in the clinical evaluation of obesity. Individuals suffering from metabolically unhealthy obesity (MUO) are at an excess risk of developing cardiovascular diseases (CVDs), several cancer types, and metabolic syndrome (MetS), whereas the metabolically healthy obesity (MHO) phenotype has a high risk of all-cause mortality and cardiometabolic events but not MetS. While most obese individuals have the MUO phenotype, the frequency of the MHO phenotype is at most 10-20%. Over time, approximately three-quarters of obese individuals transform from MHO to MUO. Total adiposity and truncal subcutaneous fat accumulation during adolescence are positively and independently associated with atherosclerosis in adulthood. Obesity, in general, causes a large reduction in life expectancy. However, the mortality rate of morbid obesity is greater among younger than older adults. Insulin resistance (IR) develops with the central accumulation of body fat. MHO patients are insulin-sensitive like healthy normal-weight individuals and have lower visceral fat content and cardiovascular consequences than do the majority of MUO patients. MetS includes clustering of abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. The average incidence of MetS is 3%, with a 1.5-fold increase in the risk of death from all causes in these patients. If lifestyle modifications, dietary habits, and pharmacotherapy do not provide any benefit, then bariatric surgery is recommended to reduce weight and improve comorbid diseases. However, obesity treatment should be continuous in obese patients by monitoring the accompanying diseases and their consequences. In addition to sodium-glucose co-transporter-2 (SGLT2) inhibitors, the long-acting glucagon-like peptide-1 (GLP-1) receptor agonist reduces the mean body weight. However, caloric restriction provides more favorable improvement in body composition than does treatment with the GLP-1 receptor (GLP1R) agonist alone. Combination therapy with orlistat and phentermine are the US Food and Drug Administration (FDA)-approved anti-obesity drugs. Recombinant leptin and synthetic melanocortin-4-receptor agonists are used in rarely occurring, monogenic obesity, which is due to loss of function in the leptin-melanocortin pathway.