12.1.4 Assessment and management of severe obesity in adults

Body weight is determined by an interaction between genetic, environmental, and psychosocial factors acting through the physiological mediators of energy intake and expenditure (1). By definition, obesity results from an imbalance between energy intake and energy expenditure and in any individual, excessive caloric intake or low energy expenditure, or both, may explain the development of obesity. A third factor, nutrient partitioning, a term reflecting the propensity to store excess energy as fat rather than lean tissue, may contribute.

For the assessment of severely obese patients, the consultation room should be properly equipped with larger than average chairs, access for wheelchairs for patients with mobility problems, and medical equipment of appropriate size (examination couch, blood pressure cuff, weighing scales, stadiometer, and tape measure). A general medical history should address the potential complications of severe obesity such as sleep apnoea, coronary heart disease, type 2 diabetes, gynaecological abnormalities, osteoarthritis, gallstones, and stress incontinence (Box 12.1.4.1). A specific weight history should be taken carefully establishing the age of onset as it is useful to distinguish early-onset obesity (before aged 10 years) as this has a stronger genetic component, from that occurring later in life either in relation to specific physiological ‘critical periods’ such as pregnancy, illness or concomitant medications. A history of previous treatment for obesity, and diet and levels of physical activity should be noted.

Height should be measured accurately using a stadiometer and weight measured by accurate scales that have been calibrated against known weights. Fat distribution is assessed by measurement of the waist circumference and is used to refine an assessment of risk for patients with a body mass index (BMI) of 25–34.9 kg/m². Waist circumference is taken as the midpoint between the lower rib margin and the iliac crest. An examination of the skin is important: thin, atrophic skin is a feature of excess corticosteroids; acanthosis nigricans (pigmented ‘velvety’ skin creases, especially in the axillae) suggests insulin resistance; and severe hirsutism in women may indicate polycystic ovary syndrome. A neck circumference of more than 43 cm indicates a likelihood of obstructive sleep apnoea. Clinical examination for signs of other obesity-associated complications is important (Table 12.1.4.1).

Clinicians should use laboratory testing to evaluate overweight and obese patients who may be at high risk for cardiovascular disease, diabetes, and thyroid disease. Some useful tests to consider are fasting plasma glucose or 2-h postprandial glucose levels and serum lipid levels. Thyroid-stimulating hormone may be helpful in excluding hypothyroidism. Urinary free cortisol can be obtained if hypercortisolism is suspected. Other tests to consider depend on clinical assessment and include ultrasound for hepatic steatosis, gallstones, and the polycystic ovary syndrome; electrocardiography in patients at high risk for cardiovascular disease; polysomnography for patients with possible sleep apnoea; and CT or MRI of the head when pituitary or hypothalamic disorders are suspected. Genetic testing is needed to confirm the diagnosis in patients with rare genetic disorders.

The recommendation to treat obesity is based on evidence that relates obesity to increased mortality and the results of randomized controlled trials which demonstrate that weight loss reduces the risk of disease (2, 3). Professional, governmental, and other bodies have drawn up guidelines for obesity management and its advisable to seek out the latest national and international guidelines as newer evidence is incorporated. These strategies provide useful evidence-based guidance for clinical management, however, it is important to remember that an individually tailored approach is often required and that any treatment programme for obese patients should address both weight reduction and the maintenance of the lowered weight and take account of individual circumstances.

Achievement of normal or ideal body weight is not a necessary goal in the management of obesity, and is rarely reached in practice. There is evidence from epidemiological studies of intentional weight loss that modest weight loss, in the order of 5–10% from presentation weight (4), is associated with clinically worthwhile reductions in comorbidities, such as hypertension, dyslipidaemia, and diabetes risk (Table 12.1.4.2). In some patients, particularly in those with severe co-morbidity, prevention of weight gain may be a reasonable aim of treatment. Weight loss should be approached incrementally with new goals for weight loss negotiated with the patient once the original target has been achieved.

Recent evidence-based reviews support the use of low-calorie diets, energy-deficit diets and diets that are low in fat as being most likely to be effective for modest weight loss (5). A review of 48 randomized controlled trials showed that an average weight loss of 8% of the initial body weight can be obtained over 3–12 months with a low-calorie diet, and that this weight loss can lead to a decrease in abdominal fat (6). Such a treatment may require a period of supervision for at least 6 months. The weight-reducing dietary regimen tailored to an individual’s need should initially provide a 600 kcal/day (2.5 MJ/day) energy deficit, based on estimated energy requirements. After 6 months, the rate of weight loss usually declines and a further adjustment of calorie intake may be indicated at this stage. The use of very-low-calorie diets can be considered but their use should follow all of the recommendations from the Committee on Medical Aspects of Food Policy, in particular that such preparations must provide a minimum of 400 kcal (1.7 MJ) per day for women and 500 kcal (2.1 MJ) per day for men. Evidence from randomized trials confirms that over the longer term (more than a year) weight loss following very-low-calorie diets is no different from that obtained with a low-calorie diet.

Behavioural approaches aim to help subjects to implement and sustain changes to their eating and activity behaviour and require trained health professionals with good interpersonal skills to use the approach appropriately and in a supportive manner. There is evidence that combining a behavioural approach with more traditional dietary and activity advice leads to improved short-term weight loss. However, these studies are of relatively short duration, so the evidence base is limited to 1 year at present. In general, weight loss with these approaches is modest (about 4 kg or 4% of body weight on average).

Although modest physical activity has undoubted health benefits and can contribute to weight loss, it is not usually advocated as a sole treatment option. Many studies, however, do suggest that it can be helpful to improve weight loss maintenance, although activity levels equivalent to 45–60 min of brisk walking each day may be needed to achieve this. The results from randomized controlled trials suggest that a combination of diet and exercise generally produces more weight loss than diet alone.

The use of obesity drugs should follow the same principles as for any condition and be prescribed after assessment of the potential benefits and risks with appropriately informed patients, and with medical monitoring of the results of treatment (7). Many people, including doctors, still believe that a short course of drug treatment might ‘cure’ obesity or that efficacy is measured only by ever-continuing weight loss. These ideas are inconsistent with the known biology as people who become obese have a lifelong tendency both to defend their excess weight and to continue to gain extra body fat. Effective management must be lifelong and focused on weight loss maintenance in a similar fashion to the effective treatment for hypertension or diabetes. Starting drug treatment should always be regarded as a therapeutic trial and stopped if weight loss is not apparent after 1–2 months. The initiation of drug treatment will depend on the physician’s judgement about the risks to an individual from continuing obesity. A drug should not be considered ineffective because weight loss has stopped, provided that the lowered weight is maintained. However, continuation of the drug should depend on the balance between the health benefits of maintained weight and the potential adverse effects of the drug.

Orlistat inhibits pancreatic and gastric lipases, decreasing the hydrolysis of ingested triglycerides. It produces a dose-dependent reduction in absorption of dietary fat that is near maximum at a dose of 120 mg three times daily. It leads to 5–10% weight loss in 50–60% of patients, and in clinical trials the loss (and related clinical benefit) is largely maintained up to at least 4 years. Adverse effects of orlistat are predominantly related to malabsorption of fat. These include loose or liquid stools, faecal urgency, and oily discharge; they can be associated with malabsorption of fat-soluble vitamins. As the consumption of a high-fat meal will inevitably lead to severe gastrointestinal symptoms, it is possible that some of the weight loss with orlistat treatment results from an ‘antabuse effect’, leading to behavioural change.

Sibutramine inhibits the reuptake of noradrenaline and serotonin, promoting and prolonging satiety. It may also have an enhancing effect on thermogenesis through the stimulation of peripheral noradrenergic receptors. In a meta-analysis of 10 randomized controlled trials each lasting more than 1 year, subjects in the sibutramine group lost 4.2 kg (95% CI 3.6 kg to 4.7 kg) more than those in the placebo group. There is also evidence that sibutramine aids weight maintenance after diet- induced weight reduction, although after therapy discontinuation a proportion of the lost weight may be regained (8).

However, due to concerns about the increased risk of cardiovascular events associated with the prescription of sibutramine, the drug is no longer licensed for the treatment for obesity in Europe and North America.

Clinical trials are now well advanced for several drugs with different modes of action. Many of the hormones and hormone receptors that contribute to regulation of appetite or satiety are targets for drug treatment and under active development in preclinical and early clinical trials. Newer agents primarily designed to treat diabetes, such as the synthetic amylin pramlintide and glucagon-like peptide-1 (GLP-1) analogue exenatide, are licensed in some countries and lead to clinically important weight loss. There is also interest in gut-derived peptides such as oxyntomodulin to improve satiety. Most obese people have high concentrations of leptin, but early trials of leptin supplementation in common obesity were disappointing. However, leptin may prove to be useful in combination with other drugs and as an adjunct to weight-maintenance strategies.

Randomized controlled trials confirm that surgery for obesity is an option for carefully selected patients with severe obesity (BMI >40 kg/m² or BMI >35 kg/m² with comorbid conditions) (9). The nature of the surgical procedures necessitates long-term hospital follow-up for such patients. The initial findings from the Swedish Obese Subjects study of severely obese subjects (those with a BMI of more than 40 kg/m²) indicate that weight loss of approximately 30 kg over 2 years is associated with a 60% reduction in plasma insulin, a 25% decrease in plasma glucose and triglycerides, and a 10% reduction in blood pressure, with associated effects on the risk of cardiovascular disease. Poor health-related quality of life was greatly improved after gastric restriction surgery, while only minor fluctuations in health-related quality of life were observed in subjects treated by conventional dietary methods. In obese subjects with type 2 diabetes undergoing bariatric surgery, there is frequently a rapid resolution of diabetes that occurs prior to significant weight loss. This finding as well as the substantial and pervasive weight loss which occurs following surgery may in part be due to an alteration in the secretion of pro-satiety gut hormones such as peptide-YY (PYY) and GLP-1 and changes in intestinal gluconeogenesis, in addition to the structural surgical changes. Most surgical treatment is now carried out laparoscopically. Three approaches are widely used.

This operation involves gastric restriction with the creation of a small compartment (less than 20 ml) by either a combination of vertical stapling and a constrictive band opening or a gastric band pinching off a small proximal pouch. A modification of the latter procedure is an inflatable gastric band attached to a subcutaneous reservoir which allows access by a hypodermic syringe to inject or withdraw fluid thereby tightening or enlarging the band width. This method mainly works by restricting how much food patients can eat. The average weight loss is around 15–20% of body weight, although some weight regain occurs over time. Morbidity and mortality are relatively low (mortality <0.2%), but patients do need to return for band adjustments.

This involves creating a small-volume gastric pouch and producing a Roux-en-Y diversion so that food bypasses the duodenum and upper jejunum. This works by both restricting food intake and causing a modest degree of malabsorption. Weight loss is generally greater than with the band. Operative mortality is <0.2% for laparoscopic procedures and 0.5% for open procedures.

A variant of the older biliopancreatic diversion, this involves a partial (sleeve gastrectomy) bypass of a long loop of jejunum. Weight loss is greatest with this procedure, but malabsorption is more likely and patients need careful follow-up and attention to their diet, and vitamin and mineral supplementation.

As the prevalence of obesity is rising, we are seeing a greater proportion of patients with severe obesity. It is important to have a practical approach to the investigation and management of these vulnerable patients who have considerably increased morbidity and mortality. The clinical evaluation of the severely obese patient will become increasingly sophisticated and novel biochemical and molecular genetic diagnostics will need to be combined with the more traditional nutritional and behavioural approaches to optimize treatment for individual patients. Aside from bariatric surgery there currently exists no truly efficacious long-term therapy for the treatment of obesity. Studies of the physiological system that regulates weight have identified several molecules that have potential as therapeutic targets and it is likely that as additional components of the system that regulate body weight are identified, new therapeutic modalities will emerge.