Obesity - Clinical Review

Over the last few decades, the prevalence of obesity has been increasing rapidly, reaching epidemic proportions worldwide. About 1.6 billion people in the world today are overweight and 400 million obese.(1)

Genetic conditions like Prader-Willi syndrome predispose to obesity
Genetic conditions like Prader-Willi syndrome predispose to obesity

Section 1: Aetiology and epidemiology

In England, a quarter of adults are obese and, if current trends continue, 60 per cent of adult males, 50 per cent of females and 25 per cent of children will be obese by 2050.2

Obesity is the most common disorder of childhood and adolescence; in 2007, 15.4 per cent of children in England were obese and 28.6 per cent were overweight. The epidemic is closely linked to the rapid rise in the prevalence of serious co-morbidities such as type-2 diabetes and sleep apnoea. Obesity is now the most important cause of maternal mortality.

The financial burden on the NHS is already very significant and could increase seven-fold by 2050.

Definition and classification
Obesity can be defined in simple terms as an excessive amount of body fat, which is associated with increased risk of medical illness and premature death. Clinically, obesity is defined as a BMI of 30 and above. Overweight is defined as BMI of between 25 and 30.

Increasing levels of obesity (Class I = 30-34.9, Class II = 35-39.9 and Class III ≥40) are associated with increasing risk of related diseases and mortality. In those with BMI <35, further classification based on waist circumference is useful to stratify risk, as central obesity is a more accurate predictor of mortality and morbidity than BMI alone.

In some ethnic groups (such as people from Asia and Pacific regions), the risk of co-morbidities and mortality is greater at much lower BMI levels.

Aetiology of weight gain
The underlying cause of weight gain is often multifactorial. In simplistic terms, weight gain results from excess energy available for storage, often due to energy imbalance (excess energy intake, reduced energy expenditure or both) over a long period.

Energy balance is influenced by factors such as genetic predisposition, illness, drugs, lifestyle choices, environmental and socioeconomic factors.

Weight gain factors
Aetiology of obesity and factors predisposing to weight gain

  • Genetic factors

Syndromes such as Prader-Willi, Bardet-Biedl; single gene defects such as leptin deficiency, leptin receptor (LEPR) mutations, POMC gene defects, MC4R defects; inherited traits; new interests like FTO gene (fat mass and obesity-associated gene) variants, INSIG2 gene (insulin induced gene 2).

  • Fetal and infant origins

Intrauterine growth, fetal under-/over-nutrition, maternal smoking, birth weight, breastfeeding, rate of growth in early childhood, social status.

  • Environmental factors

Increase in high-calorie food intake, increased proportion of fat intake at the expense of complex carbohydrates, availability of energy-dense ready meals and vending machines, reliance on convenience food and high-calorie snacks, reduced physical activity, labour saving devices, transport facilities, change in work patterns, sleep deprivation, smoking cessation and less-active leisure time pursuits.

  •  Behavioural and psychosocial factors including eating disorders.
  • Novel theories

Altered intestinal flora (rich in firmicutes species and relatively deficient in bacteroides) and adenovirus AD-36.

  • Secondary causes
  • Endocrine disease: hypothyroidism, Cushing's syndrome, acromegaly, growth hormone deficiency, hypogonadism and polycystic ovarian syndrome (PCOS).
  • Hypothalamic obesity: hypothalamic tumours, pituitary macroadenomas (with or without pituitary dysfunction), surgery and radiotherapy can affect appetite regulation.
  • Drugs: anticonvulsants, antipsychotics, antidepressants, beta-blockers, steroids, oral hypoglycaemic agents (except metformin and DPP4 inhibitors), insulin, protease inhibitors, sex hormones and contraceptive hormone preparations.
  • Pregnancy, contraception and menopause.

Section 2: Assessment and lifestyle
All healthcare professionals should recognise obesity as an important preventable health risk, and educate people about the dangers of weight gain and benefits of weight loss.

Most patients who are overweight or obese could be managed in the community. They should be offered advice about a balanced and healthy diet, preferably by a dietitian, and should be encouraged to increase their daily physical activity.

Weight loss medication can be offered to those who are unable to lose weight with lifestyle modification. Referral to a specialist centre may be helpful for those who are very obese, or where there is suspicion of secondary causes or an eating disorder, severe obesity-related co-morbidities, or if surgical intervention is being considered.

Detailed assessment
As the aetiology of obesity is multifactorial, a detailed assessment of the patient is an essential first step. Screening for secondary causes and contributory factors is important. Details of family history, lifestyle events coinciding with onset of weight gain (marriage, divorce, employment, childbirth) and psychosocial factors are helpful.

In addition to assessment of co-morbidities, a thorough assessment of lifestyle factors is essential. History of previous successful or failed attempts offers valuable insight into the causes of relapses and problems with weight maintenance.

The level of intervention is influenced by severity of obesity, presence of co-morbidities and complications, reasons for wanting to lose weight, expectations and motivation for change.

Lifestyle interventions
Dietary education is an essential component of any treatment.

Commercial dietary programmes such as very-low-calorie diets (VLCDs), low glycaemic-index diets, high-protein diets and meal replacement plans have gained acceptance recently. These are usually effective in the short-term but problems with maintenance in the long-term are documented.

Commercial programmes involving significant calorie restriction or manipulation of dietary composition can be harmful to patients without appropriate monitoring. Modest calorie restriction and adherence to long-term healthy dietary changes is more likely to be effective in weight-loss maintenance than 'yo-yo dieting'.

Daily physical activity to increase energy expenditure offers additional benefits. Apart from weight loss, several obesity-related co-morbidities can be improved or prevented by modest exercise.

Regular physical exercise is essential in obesity prevention and weight loss maintenance. Obese patients should focus on improving their cardiovascular 'fitness' rather than measures of 'fatness' such as bodyweight and dress size.

Moderate intensity physical activity for 30 minutes daily or 45 to 60 minutes three times a week is recommended for weight management.3

Behaviour therapy can improve outcomes. It includes strategies such as self-monitoring, record keeping, problem solving, stimulus control, stress management and cognitive restructuring. It improves compliance and confidence.

People with obvious eating disorders such as binge-eating and bulimia are best managed by psychologists, as they often require prolonged and individualised cognitive behaviour or analytic therapy, but any successful weight management plan should involve at least some degree of behavioural modification.

Section 3: Management
There are two drugs licensed for prolonged use in obesity management. They should be used only in combination with lifestyle education and careful monitoring.

Orlistat is available on prescription (120mg three times daily) or as an OTC preparation (60mg three times daily). It inhibits pancreatic and intestinal lipases, resulting in inhibition of absorption of about 30 per cent of dietary triglycerides. It should not be used in the presence of chronic malabsorption syndrome or cholestasis.

It is better to prescribe this after people have made dietary changes (limiting fat intake) with the help of a dietitian, to minimise GI side-effects.

When combined with lifestyle modification, it causes a modest weight loss of 3.5kg over placebo; 58 per cent achieve 5 per cent weight loss and 39 per cent achieve 10 per cent weight loss.4

Orlistat can contribute to improvement in glycaemic control in patients with diabetes and modestly reduces cholesterol and BP. Current evidence supports use for up to 48 months, but it may be considered for long-term weight maintenance if there is a risk of weight regain on completion of therapy.

Sibutramine is a centrally acting inhibitor of serotonin and noradrenaline reuptake. It limits food intake by enhancement of the natural satiety process. It is started at 10mg daily, which can be increased to 15mg if there is less than 2kg weight loss in the first four weeks of treatment.

It should not be used in patients with severe hepatic/renal impairment, eating disorders, psychiatric illness, vascular disease, uncontrolled hypertension, arrhythmias or those taking antidepressants or antipsychotics.

BP and heart rate should be monitored fortnightly in the first three months and periodically thereafter. Treatment should be stopped if there is a persistent rise in either (10mmHg systolic or diastolic BP, or a 10bpm rise in heart rate).

When combined with lifestyle advice, mean weight loss after 24 weeks' treatment is 6.1 per cent (10mg) and 7.4 per cent (15mg).5

The recommended duration of treatment is 12 months but current evidence supports use for up to two years.

Sibutramine may improve glycaemic control in diabetes and appears to have beneficial effects on the lipid profile.

Surgical management
Until recently, bariatric surgery was considered a high-risk option reserved for extreme cases.

Weight loss surgery has now become increasingly acceptable. Minimally invasive laparoscopic techniques and improved peri-operative care have improved safety. Published outcome data show reduced morbidity and mortality compared with non-surgically treated patients and surgery is now considered cost-effective for severe obesity.

Careful selection of patients likely to benefit from surgical intervention is important.

NICE guidelines recommend surgery for patients with a BMI >40 (>35 with comorbidities likely to improve with weight loss, such as diabetes) after all other measures have been tried unsuccessfully, or as a first-line intervention if the BMI >50.3

Patients must be capable of making the significant lifestyle changes required to succeed after surgery. Most require intensive management in a specialist centre before surgery.3

Malabsorptive procedures are more effective than restrictive procedures but tend to have higher morbidity and mortality risk.6,7 However the benefits clearly outweigh the risk in very obese patients and those with serious co-morbidities.

Section 4: Future of obesity management
Understanding of appetite regulation and how it contributes to the pathophysiology of obesity is improving due to advances in genetic research, novel animal models and functional neuro-imaging techniques.

Early trials of some newer pharmacotherapeutic agents such as serotonin-noradrenaline-dopamine reuptake inhibitors, neuropeptide Y antagonists, SSRIs and combination therapies with peptide analogues of natural hormones involved in weight regulation including amylin, peptide YY, glucagon-like peptide-1 and leptin are promising.

Improved surgical techniques such as robotic surgery and sleeve gastrectomy and ileal interposition are promising to improve efficacy and safety of bariatric surgery. Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an exciting development that could offer the benefits of bariatric surgery with significantly lower risk.

Sustained weight loss
With surgery, people are experiencing dramatic weight loss. Current evidence confirms sustained weight loss up to 15 years along with remission or durable improvements in diabetes, dyslipidaemia, obstructive sleep apnoea, cancer risk, cardio-respiratory function, fertility, mobility, psychosocial performance and quality of life.8

However, long-term follow up is vital due to the need for constant titration of treatment and risk of recurrence of comorbidities and weight regain.

Long-term effects of surgery and newer treatments are not fully known. Healthcare professionals need to keep themselves fully aware of latest developments in obesity management and monitoring.

  • 2-8 November is National Obesity week. For more information visit www.nof.uk.com
  • Contributed by Dr Bhandari Sumer Aditya, consultant physician, and Professor John PH Wilding, professor of medicine and honorary consultant physician, University of Liverpool, University Hospital Aintree, Liverpool.


1. WHO - Obesity and Overweight. Factsheet No 311. Sep 2006.

2. Foresight. Tackling Obesities: Future Choices - Project Report, The Stationery Office, London, 2007.

3. NICE clinical guideline 43 Obesity. Dec 2006. www.nice.org.uk/cg43

4. Sjostrom L, Rissanen A, Andersen T et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 1998; 352(9123): 167-72.

5. James WP, Astrup A, Finer N et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 2000; 356(9248): 2119-25.

6. Buchwald H, Estok R, Fahrbach K et al. Weight and type-2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009; 122(3): 248-56.

7. Buchwald H, Estok R, Fahrbach K et al. Trends in mortality in bariatric surgery: a systematic review and meta-analysis. Surgery 2007; 142(4): 621-32.

8. Sjostrom L, Narbro K, Sjostrom CD et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357(8): 741-52.

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