Obesity

Excess weight. Arbitrarily defined as a BMI >30. Generally a result of excess calorie intake in relation to energy expenditure. In England, the Health Survery showed that 23.8% of the population was classified as obese.

Distribution of body mass may also be important, with some evidence suggesting that a "pear-shaped" fat distribution - with the fat predominantly on the buttocks and legs - may be less associated with some diseases than an "apple-shaped" fat distribution, with more abdominal fat; or that waist measurements may be more significant than body weight. Whatever wrist to hip ratio (WHR) is a better predictor of mortality than BMI over 14 years follow-up^[1]

Apart from mortality which as a "J shaped" relationship to BMI^[2], obesity increases the risk of several other conditions with most of the cardiovascular risk being related in turn to secondary diabetes mellitus and hypertension.

• Hypertension
• Diabetes mellitus
• Osteoarthritis
• Cardiovascular disease (BMI is NOT an independent risk factor for mortality)
• Obstructive sleep apnoea
• Dyspepsia (and see below for risk of continued reflux)

• Cancer - BMI is independent risk factor for mortality
  • Most of excess risk with BMI > 40
  • Cancers whose risk most increased are:^[3]
    • Uterine cancer in women
    • Liver cancer in men
    • Kidney cancer in woman
    • Cervical cancer in woman
    • Pancreatic cancer both sexes
    • Oesophageal cancer both sexes

Contents 1 Aetiology 1.1 Genetics 1.1.1 Monogenetic 1.1.2 Polygenetic 1.2 Environment 1.3 Behaviour 2 Treatment 3 Obesity as a contraindication to treatment 3.1 Treatments that do not work 4 References

Aetiology

Extremely complex interaction between genetics, environment and individual behaviour. Examples of such factors follow to give a flavour rather than suggest any are important in an individual. The hypothalamic leptin/melanocortin pathway is only thought to be important in a minority. There is a strong genetic component (40 to 80% heritability).

Genetics

The strongest genomewide associations of body mass index are with introns 1 and 2 of the gene FTO. This modulates a pathway of adipocyte thermogenesis regulation coded by genes including ARID5B, IRX3, and IRX5^[4]. Mitochondrial thermogenesis is also regulated by the genes that control the expression of uncoupling protein 1 coded by UCP1 which include IRF4, PRDM16, and TBX15.

Monogenetic

• Melanocortin 4 receptor (MC4R) mutations^[5] - commonest monogenetic cause of obesity -adult prevalence in the extremely obese about 2.5%^[6]
• Leptin deficiency^[7][8]
• Leptin receptor (LEPR) deficiency^[9]
• Pro-opiomelanocortine (POMC) gene
• Prohormone convertase 1 (PC1) gene

Polygenetic

• Prader-Willi syndrome
• Bardet-Biedl syndrome
• Β-3 adrenergic receptor varients in women
• Uncoupling protein-1
• Regulator regions of the leptin gene
• Low-density lipoprotein receptor in women
• Tumour necrosis factor alpha in women
• INSIG2 gene^[10]

Environment

• Gut microflora^[11]
• Dietary habits^[12],
• Sedentarism
• Β 2-adrenoceptors and physical activity in woman
• Antipsychotics^[13]

Behaviour

Social class/status is almost as greater a predictor of obesity as any other factor. The fact that eating behaviour can be genetically determined in some^[14]is not believed to be a major cause of this association. The only social group in Britain as of not getting more obese is professional women, emphasizing perhaps a consistency in behaviour of this social grouping over the last few decades^[15].

• Intake of high energy foods
• Intake alcohol

Treatment

You might as well keep it simple because they all work if you stick with them !^[16]

1. Diet and exercise^[17][18]
2. Drugs. There are no magic pills. Indeed more drugs have been withdrawn from market in this indication recently than most others.
   • Appetite suppressant
   • Drugs that reduce intestinal absorption
3. Bariatric surgery^[19]
   • Works but takes at least three years to give return on investment from health economic point of view

Obesity as a contraindication to treatment

Obesity may:

• Reduce the likelihood that a treatment will work, sometimes to the extent that it is not worth providing, or may not be cost-effective.
• Increase the risk of adverse reactions.

Obesity may therefore be a relative or absolute contraindication. However for interventions such as total hip replacement, once all the other conditions associated with obesity such as ischaemic heart disease and diabetes are corrected for, being over weight is probably protective^[20].

For example, when considering the use of combined oral contraceptives:^[21]

• A body mass index of Body mass index ≥ 30 - 34 kg/m2 comprises "A condition where the advantages of using the method generally outweigh the the theoretical or proven risks";
• A body mass index 35 – 39 kg/m2 comprises "A condition where the theoretical or proven risks usually outweigh the advantages of using the method"; and
• A body mass index ≥ 40 kg/m2 comprises "A condition which represents an unacceptable health risk if the contraceptive method is used".

Treatments that do not work

Weight loss is associated with smoking. However the risks of the treatment (smoking) easily outweighs the benefit in terms of weight reduction. Mortality in diabetic smokers and non-smokers has been explored in detail as a function of body mass index. Once early deaths are eliminated we find that the J shaped curve in mortality as related to BMI is almost totally driven by low BMI smokers. Non smokers have a close to linear relationship between BMI and increased mortality^[22]. In other words those diabetics with a low body mass index (BMI between 18.5 to 22.4) and who smoke are at much higher risk of mortality than those diabetics whose BMI is low for non pathological reasons.

References