Does obesity have a genetic origin?

Although many obese individuals are blamed for being obese—by their friends, physicians, family and by themselves—increasingly it has been shown that genetic influences have a substantial influence on BMI. The ob gene is an adipocyte-specific gene that encodes leptin, a protein that regulates body weight. Animals with mutations in ob are obese and lose weight when given leptin (Nature 1994;372:425–32). In humans, serum leptin concentrations correlate with the percentage of body fat, suggesting that most obese people are insensitive to endogenous leptin (leptin resistance).

What is the body mass index?

It is a measure to determine the presence of excessive adipose tissue and is calculated by dividing the body weight in kilograms by the height in metres squared. The normal spread of the BMI is from 20 to 25 kg/m².

What is morbid obesity?

It is relative weight greater than 200% (or BMI >40) and is associated with a 10-fold increase in the mortality rate.

Mention some adverse health consequences of obesity

They have a greater risk for diabetes mellitus (Fig. 148.1), stroke, coronary artery disease, premature mortality, thromboembolism, gallstones, reflux oesophagitis, sleep apnoea, polycythaemia and cancer of the colon, rectum, prostate, uterus, breast and ovary. The risk of death from all causes is increased and the risk is associated with a high BMI is greater for whites than black. Also higher maternal weight before pregnancy increases the risk of late fetal death, although it protects against delivery of a small-for-gestational age infant.

Fig. 148.1 Relative risk of developing type 2 diabetes with increasing body mass index (BMI) and waist circumference.

How common is obesity?

Obesity is becoming increasing common all over the world, particularly in the USA. About one-third of US adults ≥20 years of age are now obese. Obesity rates significantly increased between 1988–1994 and 2005–2008: by 69.3% among adults 20–39 years of age, 36.9% among those 40–59 years of age, and 44.7% among those ≥60 years. Such trends have undoubtedly helped to drive the age-adjusted prevalence of clinically diagnosed diabetes to 59 cases per 1000 population (in 2008), far above the baseline of 40 cases per 1000 (in 1997).

What patterns of obesity correlate with premature coronary artery disease?

Central obesity (abdomen and flank) and when there is excessive visceral fat within the abdominal cavity rather than subcutaneous fat around the abdomen.

How would you manage such patients?

Approach is based on BMI and comorbidities such as cardiovascular disease (Fig. 148.2):

Fig. 148.2 Therapeutic options for obesity with increasing body mass index (BMI) and comorbidity.

Note: Jejuno-ileal bypass is rarely used.

What are the mechanisms of obesity?

The pathophysiology of obesity is complex and poorly understood, but it includes genetic, behavioural, psychological and other factors:

Mutation in the gene for the nuclear receptor perioxisome proliferator-activated receptor-γ accelerates differentiation of adiopocytes and may cause obesity (N Engl J Med 1998;339:953–9). The thizoladinedione class of antidiabetic drugs act at this point.

Mention some syndromes where obesity is a prominent feature

Cushing syndrome (p. 538), Laurence–Moon–Biedl syndrome (p. 724), Pickwickian syndrome (p. 410), Alstrom syndrome, Prader–Willi syndrome.

What is the link between obesity and diabetes?

Fat cells release free fatty acids and tumour necrosis factor-α, which cause insulin resistance, and leptin, which causes insulin sensitivity. A protein called resistin that is secreted by fat cells also causes insulin resistance. The antidiabetic group of drugs, the thiazoladinediones, reduce insulin resistance by suppressing the expression of resistin by the fat cells (Nature 2001;409:307–12).