53: Obesity

Key Points

• Disease summary:

  • Common obesity has conventionally been viewed as a disease that is caused by substantial changes in the human environment, for example, the increase in consumption of calorie-rich food and decrease in physical activity. There is also strong evidence that genes are critically involved in the development of obesity.

    • Obesity is a major risk factor for cardiovascular diseases, pulmonary diseases (such as sleep apnea), metabolic diseases (eg, diabetes and dyslipidemia), osteoarticular diseases, for several of the commonest forms of cancer, and for serious psychiatric illness.

• Differential diagnosis:

  • It includes depression, diabetes mellitus, type 1, diabetes mellitus, type 2, fatty liver, growth hormone deficiency, hiatal hernia, hirsutism, polygenic hypercholesterolemia, hypertension, hypothyroidism, insulinoma, Kallmann syndrome, and idiopathic hypogonadotropic hypogonadism, generalized lipodystrophy, nephrotic syndrome, polycystic ovarian disease (Stein-Leventhal syndrome), pseudo-Cushing syndrome, adiposa dolorosa (Dercum disease), partial lipodystrophies associated with localized lipohypertrophy.

• Monogenic forms:

  • They explain at least 5% of obesity cases.

• Family history:

  • The risk of developing obesity has been shown to be doubled if a person has a first-degree relative who is overweight, tripled if your first-degree relative is moderately obese, and five times greater if first-degree relative is morbidly obese.

• Twin studies:

  • Twins studies of human obesity have shown that the heritability of body mass index (BMI) is between 0.5 and 0.8. It was also shown that the concordance rate between monozygotic twin pairs is more than twice that of dizygotic pairs (~0.68 vs ~0.28).

• Environmental factors:

  • Change in lifestyle, decline in physical activity, and abundance of fat-rich foods have been regarded as the three major components of the obesogenic environment. In addition, there are other risk factors for development of obesity that include age, gender, sleep duration, antidepression drug consumption, exposure to chemicals, and ethnicity.

• Genome-wide associations: A main role in genome-wide association studies (GWAS) is in hypothesis generations and the putative genes identified that have shed novel insights in disease etiology, although additional studies would be necessary to prove and determine mechanistic roles. Many associations exist with obesity and have provided a valuable contribution in the area of genetics of obesity by effectively identifying several putative genetic loci associated with the common polygenic form of obesity (Table 53-1).

• Pharmacogenomics:

  • Testing for leptin gene mutations that causes leptin deficiency (Table 53-2)