Look at this patient.



· Family history of obesity (parental obesity more than doubles the risk of adult

obesity among both obese and non-obese children under 10 years of age, N Engl

J Med 1997; 337: 869-73).

· History of sleep apnoea, snoring and insomnia.

· History of hypertension, diabetes, hyperlipidaemia, cardiovascular disease.

· Gastro-oesophageal reflux.

· History of gallstones (cholesterol gallstones more prevalent in obesity).

· History of endometrial cancer in women (two to three times more common in

obese than in lean women).

· History of breast cancer (risk increases with body mass index in postmenopausal


· Cancer of gallbladder and biliary system (obese women have a higher incidence).

· Cancer of colon, rectum and prostate, and renal cell cancer (N Engl J Med 2000;

343:1305-11) (higher in obese men).


Patient has excessive adipose tissue.

Proceed as follows:

· Measure the height and body weight (to determine body mass index).

· Check blood pressure (the prevalence of hypertension is approximately three

times higher in the obese than the non-obese).

· Examine the joints to exclude osteoarthrosis.

· Examine skin for intertrigo in redundant folds of skin (fungal and yeast infections

of skin are also common).

· Tell the examiner that you would like to:

-Assess urine sugar (the prevalence of diabetes is three times higher in overweight

than in non-overweight persons).

-Check serum lipids (these patients otlen have an adverse pattern of plasma

lipoproteins that generally improves with weight loss).

-Assess pulmonary function (sleep apnoea).

-Exclude secondary causes (hypothyroidism, Cushing's syndrome, polycystic

ovary syndrome).


This patient has gross obesity (lesion) of genetic origin, complicated by hyper-tension

and osteoarthrosis.


Is obesity of 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 body mass index. The ob gene is an

adipocyte-specific gene that encodes leptin, a protein that regulates body weight.

Animals with mutations in the ob gene 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

cal-culated by dividing the body weight in kilograms by the height in metres

squared. The normal spread of the body mass index is from 20 to 25 kg/m2.

What is morbid obesity?

It is relative weight greater than 200% and is associated with a ten-fold increase in

mortality rate.

Mention some adverse health consequences of obesity.

Obese people have a greater risk for diabetes mellitus, 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

associated with a high body mass index is greater for whites than blacks (N Engl J

Med 1999; 341: 1097-105). 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 (N Engl J Med 1998; 338: 147-52).

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?

· Multidisciplinary approach to weight loss: hypocaloric diets, exercise, social


· Drugs: orlistat (orlistat partially inhibits the absorption of dietary fat by binding to

pancreatic lipase in the gastrointestinal tract) (Lancet 1998; 352: 167-73).

· Surgery: vertical banded gastroplasty, gastric bypass operations.

What are the mechanisms of obesity?

· Insensitivity to leptin, presumably in the hypothalamus.

· Neuropeptide Y-induced hyperphagia.

· Deficiency of production or action of anorexigenic hypothalamic neuropeptides. ·

Increased secretion of insulin and glucocorticoid.

· Mutation in the gene for PPAR-¥ accelerates differentiation of adipocytes and may

cause obesity (N Engl J Med 1998; 339: 953-9). PPAR-¥ is peroxisome

proliferator-activated receptor-¥ and is a nuclear receptor through which the

thiazolidinedione class of antidiabetic drugs acts.

Mention some syndromes in which obesity is a prominent feature.

Cushing's syndrome , Laurence-Moon-Biedl syndrome , pickwickian syndrome, Alstrom's syndrome, Prader-Willi syndrome.

What is the link between obesity and diabetes?

Fat cells release free fatty acids and tumour necrosis factor-alpha which cause insulin

resistance, and leptin causes insulin sensitivity. A new protein called resistin that is

secreted by fat cells causes insulin resistance. A group of antidiabetic drugs, the

thiazolidinediones, reduces insulin resistance by suppressing the expression of

resistin by the fat cells (Nature 2001; 409: 307-12).