Obesity is widely regarded as a
pandemic with potentially disastrous consequences for human health. More than
20% of adults in the UK, and more than 30% in USA, are obese (i.e. body mass
index, BMI ≥ 30 kg/m2, see definition on Box 5.20. Obesity has adverse effects
on both mortality and morbidity. Changes in mortality are difficult to analyse
due to the confounding effects of lower body weight in cigarette smokers.
However, it is clear that the lowest mortality rates are seen in individuals
with a BMI of 18.5-24. Data from population studies, such as that in
Framingham, USA, show that for individuals aged between 30 and 42 years, the
risk of death increases by 1% per annum for each 0.5 kg increase in weight; for
those aged 50-62, this figure is 2%. The result is that obesity reduces life
expectancy by 7.1 years in men and 5.8 years in women amongst non-smokers, and
by 13.7 and 13.3 years respectively amongst smokers. Coronary heart disease
(Fig. 5.11) is the major cause of death but cancer rates are also increased in
the overweight, especially colorectal cancer in males and cancer of the
gallbladder, biliary tract, breast, endometrium and cervix in females. Epidemic
obesity is accompanied by an epidemic of type 2 diabetes (Box 5.20). The key
difference between these depots of fat probably lies in their vascular anatomy,
with intra-abdominal fat draining into the portal vein and thence directly to
the liver. Thus many factors which are released from adipose tissue (including
free fatty acids; 'adipokines' such as tumour necrosis factor alpha (TNF-α),
adiponectin and resistin; and steroid hormones including cortisol) may be at
higher concentration in the liver and hence induce insulin resistance and
promote type 2 diabetes (Box 5.21), although both of these are difficult to
measure reliably. The estimated average global daily supply of food energy per
person increased from ∼2350 kcal in the 1960s to ∼2800 kcal in the 1990s, but its delivery is unequal. For example, in India
it is estimated that 5% of the population receives 40% of the available food
energy, leading to obesity in the urban population in parallel with persisting
malnutrition in some rural communities. In affluent societies, a significant
proportion of this food supply is discarded. However, in the USA, the average
daily energy intake of men reportedly rose from 2450 kcal in 1971 to 2618 kcal
in 2000. Well-documented increases have occurred in portion sizes, particularly
of energy-dense foods such as drinks with high refined sugar content and
high-fat snacks. These snacks are less effective at suppressing appetite and
their consumption between normal meal times decreases the recognition of food
eaten.
Circumstantial evidence suggests that
corresponding changes in energy expenditure are important; obesity is
correlated positively with the number of hours spent watching television, and
inversely with levels of physical activity (including 'non-exercise activity
thermogenesis', i.e. fidgeting).
SOME REASONS FOR THE INCREASING PREVALENCE OF OBESITY-THE 'OBESOGENIC' ENVIRONMENT
Increasing energy intake
↑ Portion sizes
↑ Snacking and loss of regular meals
↑ Energy-dense food (mainly fat)
↑ Affluence
Decreasing energy expenditure
↑ Car ownership
↓ Walking to school/work
↑ Automation; ↓ manual labour
↓ Sports in schools
↑ Time spent on video games and watching TV
↑ Central heating
Although obese people were ridiculed in the past when they bemoaned their inability to control their weight, today there is little doubt that susceptibility to obesity, and to its adverse consequences, varies between individuals. It is not true that obese subjects have a 'slow metabolism', since their BMR is higher than that of lean subjects, but it can be argued that their metabolism is not increased as much as it needs to be following weight gain. Twin and adoption studies confirm a genetic influence on obesity. The pattern of inheritance suggests a polygenic disorder, with small contributions from a number of different genes, together accounting for 25-70% of variation in weight. Polymorphisms in > 90 genes have been implicated in obesity in single studies, and 15 of these have been replicated in more than five studies; these are genes which might influence appetite, activity levels, rates of lipid oxidation and adipocyte hyperplasia, but a clear picture of their contribution remains elusive.
A few
rare single gene disorders cause severe childhood obesity. These include
mutations of the melanocortin-4 receptor (MC4R) that accounts for approximately
5% of severe early-onset obesity, defects in the enzymes processing POMC in the
hypothalamus, and mutations in the leptin gene. The latter can be effectively
treated by leptin injections. Additional genetic conditions in which obesity is
a feature include the Prader-Willi . These patients are distinguished from
those with idiopathic obesity by their short history, with a recent marked
change in the trajectory of their adult weight.
POTENTIALLY REVERSIBLE CAUSES OF WEIGHT GAIN
Endocrine factors
Hypothyroidism
Hypothalamic tumours or injury
Cushing's syndrome
Insulinoma
Drug treatments
Tricyclic antidepressants
Corticosteroids
Sulphonylureas
Sodium valproate
Oestrogen-containing
contraceptive pill
β-blockers
