Obese people are at a higher risk of early death, mostly because of diabetes, coronary heart disease, cerebrovascular disease and otehr cardiovascular deseases. The higher the level of obesity is the greater morbidity and mortality rates are. For example, men who are 10% overweight have a 13% increased risk of death, while the increase in mortality for those 20% overweight is 25%. The rise is less in women, and in men over 65 obesity is not an independent risk factor. Weight reduction reduces this mortality and therefore should be strongly encouraged. The benefits are probably greater in more obese subjects (Table 5.14).

Clinical features

Most patients recognize their own problems, although often they are unaware of the main foods that cause obesity. Many symptoms are related to psychological problems or social pressures, such as the woman who cannot find fashionable clothes to wear.

Box 5.4 Ranges of body mass index (BMI) used to classify degrees of overweight and associated risk of co-morbidities

WHO classification	BMI (kg/m2)	Risk of co-morbidities
Overweight	25-30	Mildly increased
Obese	> 30
Class I	30-35	Moderate
Class II	35-40	Severe
Class III	> 40	Very severe

Table 5-14. Potential benefits that may result from the loss of 10 kg in patients who are initially 100 kg and suffer from co-morbidities

Mortality	20-25% fall in total mortality
	30-40% fall in diabetes-related deaths
	40-50% fall in obesity-related cancer deaths
Blood pressure	Fall of about 10 mmHg (systolic and diastolic)
Diabetes	Reduces risk of developing diabetes by > 50%
	Fall of 30-50% in fasting blood glucose
	Fall of 15% in HbA1c
Serum lipids	Fall of 10% in total cholesterol
	Fall of 15% in LDL cholesterol
	Fall of 30% in triglycerides
	Increase of 8% in HDL cholesterol

The degree of obesity can be assessed by comparison with tables of ideal weight for height, from the BMI (Box 5.4), and by measuring skinfold thickness. The latter should be measured over the middle of the triceps muscle; normal values are 20 mm in a man and 30 mm in a woman. A central distribution of body fat (a waist/hip circumference ratio of > 1.0 in men and > 0.9 in women) is associated with a higher risk of morbidity and mortality than is a more peripheral distribution of body fat (waist/hip ratio < 0.85 in men and < 0.75 in women). This is because fat located centrally, especially inside the abdomen, is more sensitive to lipolytic stimuli, with the result that the abnormalities in circulating lipids are more severe.

Table 5.15 shows the conditions and complications that are associated with obesity.

Table 5-15. Conditions and complications associated with obesity

Psychological	Hypertension
Osteoarthritis of knees and hips	Breathlessness
Varicose veins	Ischaemic heart disease
Hiatus hernia	Stroke
Gallstones	Diabetes mellitus (type 2)
Postoperative problems	Hyperlipidaemia
Back strain	Menstrual abnormalities
Accident proneness Obstructive sleep apnoea	Increased morbidity and mortality
	Increased cancer risk
	Heart failure

The metabolic syndrome (syndrome X) is a cluster of cardiovascular risk factors associated with excess fat. A commonly used definition (NCEP ATP III) defines the syndrome as the coexistence of three or more of the following five abnormalities: high blood pressure (>130/85 mmHg); elevated serum triglycerides (>1.5 g/L); serum LDL cholesterol > 0.4 g/L (men) or > 0.5 g/L (women); increased abdominal circumference > 102 cm (men) or > 88 cm (women); and impaired fasting glucose (> 1.1 g/L or > 6.1 mmol/L). It is estimated that it affects up to about a quarter of adults in the USA.

The relationship between cardiovascular disease (hypertension or ischaemic heart disease), hyperlipidaemia, smoking, physical exercise and obesity is complex. Difficulties arise in interpreting mortality figures because of the number of factors involved. Many studies do not differentiate between the types of physical exercise taken or take into account the cuff-size artefact in the measurement of blood pressure (an artefact will occur if a large cuff is not used in patients with a large arm). Nevertheless, obesity almost certainly plays a part in all of these diseases and should be treated. An exception is that stopping smoking, even if accompanied by weight gain, is more beneficial than any of the other factors. Physical fitness is also helpful, and there is some evidence to suggest that a fit obese person may have similar or even lower cardiovascular risk than a leaner unfit person.

Table 5-13. Conditions in which obesity is an associated feature

Genetic syndromes associated with hypogonadism (e.g. Prader-Willi syndrome, Laurence-Moon-Biedl syndrome)

Hypothyroidism

Cushing’s syndrome

Stein-Leventhal syndrome

Drug-induced (e.g. corticosteroids)

Hypothalamic damage (e.g. due to trauma, tumour)

Obesity is almost invariable in developing countries and almost all people accumulate some fat as they get older. The World Health Organization also acknowledges that obesity (body mass index > 30 kg/m2) is a world-wide problem which also affects many developing countries. Obesity implies an excess storage of fat, and this can most easily be detected by looking at the undressed patient.

Most patients suffer from simple obesity, but in certain conditions obesity is an associated feature (Table 5.13). Even in the latter situation, the intake of calories must have exceeded energy expenditure over a prolonged period of time. Hormonal imbalance is often incriminated in women (e.g. postmenopause or when taking contraceptive pills), but most weight gain in such cases is usually small and due to water retention.
Not all obese people eat more than the average person, but all obviously eat more than they need.

Suggested mechanisms
Genetic and environmental factors

These have always been difficult to separate when studying obesity. However, refeeding experiments in both monozygotic and dizygotic twins, reared together or apart, suggest that genetic influences account for 70% of the difference in body mass index (BMI) later in life, and that the childhood environment has little or no influence.

These refeeding experiments also showed that weight gain did not occur in all pairs of twins, suggesting that in some a facultative increase in thermogenesis occurred so that part of their extra dietary energy was expended inefficiently. Genetic factors have led to the discovery of a putative gene, firstly in the obese (ob ob) mouse and now in humans. The ob gene was shown to be expressed solely in both white and brown adipose tissue. The ob gene is found on chromosome 7 and produces a 16 kDa protein called leptin. In the ob ob mouse a mutation in the ob gene leads to production of a non-functioning protein. Administration of normal leptin to these obese mice reduces food intake and corrects the obesity. A similar situation has been described in a very rare genetic condition causing obesity in humans, in which leptin is not expressed.

In massively obese subjects, leptin mRNA in subcutaneous adipose tissue is 80% higher than in controls. Plasma levels of leptin are also very high, correlating with the BMI. Weight loss due to food restriction decreases plasma levels of leptin. However, in contrast to the ob ob mouse, the leptin structure is normal, and abnormalities in leptin are not the prime cause of human obesity.

Leptin secreted from fat cells was thought to act as a feedback mechanism between the adipose tissue and the brain, acting as a ‘lipostat’ (adipostat), controlling fat stores by regulating hunger and satiety (see below). However, many other signals are involved. It is interesting that obesity is largely restricted to humans, and animals that are domesticated or in zoos.