Obesity as a Disease
Obesity is recognised as a disease that requires treatment by World Obesity, the American Medical Association, Obesity Canada and the European Association for the Study of Obesity.
Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health. A body mass index (BMI) over 25 kg/m 2 is considered overweight, and over 30 kg/ m2 is diagnostic of obesity. The prevalence of overweight and obesity is increasing globally with an estimated 1.9 billion adults considered overweight and 650 million people living with obesity. Ireland has one of the highest levels of obesity in Europe, with 60% of adults, and more than 20% of children and young people living with overweight and obesity.
The causes of obesity are complex and multifactorial, but include biological pre-disposition (including genetic susceptibility) and environmental factors. The biological pre-disposition to obesity is highly inheritable; up to 70-80% of our BMI is determined by our genes. For people with a genetic predisposition to obesity, excess energy from food leads to an accumulation of fat in fat cells. The distribution of fat as visceral fat, cardiac fat and fat in muscles may occur as fat cells reach their maximal storage capacity. These enlarging fat cells modify core metabolic and inflammatory processes which can in turn lead to a variety of other metabolic disturbances and diseases including dyslipidaemia, hypertension and diabetes.
For those that have obesity, the physiological basis for their disease is well described. Most individuals with obesity have impaired metabolic pathways that result in disordered signaling for hunger, satiety (the feeling of fullness), and fullness (the state of fullness). For many, efforts to lose weight using diets are met with unyielding resistance or disappointing weight regain as a result of a maladapted physiology that increases hunger and reduces the metabolic rate in response to reduced calorie intake. This makes it very difficult to lose weight once it is gained, which is why the environmental changes in the last few decades have uncovered this biological pre-disposition to obesity in our population.
Our modern environment is obesogenic as a result of the wide availability of calorie dense foods, inhibition of physical activity, higher levels of stress and fewer hours of sleep, all of which can contribute to the development of obesity. These factors promote greater calorie intake and reduced physical activity, which facilitates weight gain. For those that gain weight, and are biologically pre-disposed to the disease of obesity, weight loss becomes extremely difficult. This is why preventing obesity is better than treating obesity.
If obesity develops then treatment should be considered if there is a present health impact or a risk of a decline on health. Obesity is associated with adverse health outcomes including effects on physical health, social health, mental health and interpersonal relationships. In addition to these health effects, people living with obesity experience a stigma not associated with other chronic diseases.
People with obesity are blamed for their obesity, resulting in shame and loss of self-esteem. This blame can negatively impact relationships, limit opportunities in the world of work or education, and discourage social participation. This decline in psychosocial function often seen in people with obesity can be associated with a decline in mental health.
By recognising obesity as a disease we can facilitate people to receive a medical diagnosis, access treatment and overcome stigma. The recognition of obesity as a disease may also help to reduce weight bias and stigma in the media, among health professionals, among policy makers and Governments, and in wider society. While the disease of obesity can be difficult to treat, treatments are available. The treatments for obesity can be divided into three main categories
1. Specialist Dietary Interventions
2. Pharmacotherapy3. Bariatric and Metabolic Surgery1. Specialist dietary interventions
Specialist dietary interventions can be used to treat obesity, either individually, or as an adjunct to pharmacotherapy or surgery. Dietary interventions have been shown to support up to 15% weight loss. The LOOK AHEAD (Action for Health on Diabetes) trial was a randomised control trial of intensive diet and lifestyle intervention that aimed to evaluate the reduced incidence of adverse cardiovascular events among overweight or obese people with diabetes.
This study recruited over 5000 overweight individuals with diabetes and followed them up for over 9 years. The trial was stopped early as the intervention did not show a reduction in the primary outcome of adverse cardiovascular events in the intervention arm. It is worth noting that the cardiovascular event rate during the study was lower than expected which may have affected the study power. However, the study did demonstrate significant weight loss and reduced prevalence of cardiovascular risk factors and remains a gold standard in terms of dietary treatment for obesity. The intervention group achieved the most weight loss in the first year (8.6% vs 0.7% in the control group). Average weight loss after 8 years was 5% in the intervention group
However weight loss maintenance is a major challenge. Most weight was regained in the first five years post intervention at which point it stabilised at about 4-5% weight loss. A smaller proportion of people maintained greater than 10% weight loss after 8 years. An analysis of the Look AHEAD data suggested that treatment response in the first two months of treatment is strongly correlated with results after 1 year. Individuals who lose < 2% or < 3% of their bodyweight in month 2 and 3 respectively are less likely to achieve 10% weight loss after 1 year. Reviewing patients after three months on a diet and lifestyle programme would therefore be appropriate for assessing their response to the treatment.
Diets with 800 kcal per day or less are consistent with the term very low-calorie diet (VLCD). Diets with reduced calorie intakes, but with absolute intakes of over 800 kcal per day, can be termed low-calorie diets. VLCDs and low-calorie diets are usually delivered as specially formulated food products, usually in the form of milkshakes, soups or nutritional bars. The use of VLCDs and low-calorie diets can result in significant weight loss in the short to medium-term. In most studies, there is a significant drop-out rate as people can find the associated side effects of these interventions, such as constipation, to be intolerable.
However, in those who do tolerate the interventions, obesity can be successfully treated with a weight reduction of between 10 to 15% over 12 to 20 weeks of treatment. Weight maintenance following cessation of treatment can be challenging but is achievable.
Weight regain following dietary intervention appears to be mediated by physiological changes and metabolic adaptations that result in increased hunger and reduced basal metabolic rates following a period of reduced energy intake. However, despite metabolic adaptations that promote weight regain, studies have shown that weight loss maintenance is possible with ongoing dietary modification, the addition of pharmacotherapy, and concurrent exercise programmes. It should be noted that while exercise therapy may not be proven to significantly enhance weight loss during obesity treatment programmes, exercise therapy has been shown to assist with weight maintenance in the medium to long-term, which is why it is an integral element of obesity treatment programmes.
The Diabetes Remission Clinical Trial (DIRECT) was a randomised controlled study of a low calorie diet intervention completed in a primary care setting in the UK. In DIRECT, the aim was to induce remission or improve control of type II diabetes using a low-calorie diet. In this study, the intervention was a low-calorie diet of between 800 and 900 kcal per day which was prescribed for at least 12 weeks and continued for up to 5 months. Following the intervention, the participants progressed to a staged reintroduction of an isocaloric diet. A structured weight maintenance programme was then introduced and continued for up to 12 months. This intervention was compared with standard diabetes and obesity treatment that was based on lifestyle advice and diabetic pharmacotherapy.
This landmark study demonstrated that a low-calorie dietary intervention, delivered in a primary care setting with specialist support from dieticians and GPs, could deliver weight loss of 15 kg or more in 24% of participants. Almost 50% of people in DIRECT achieved remission of their Type II diabetes. This cohort were first diagnosed with Type II diabetes within six years of recruitment and diabetes remission was defined as a HbA1c of less than 6.5% (48 mmol/mol) while off all diabetes pharmacotherapy for at least two months.
While DIRECT demonstrated that such an intervention could be safely delivered in the primary care setting, it is resource intensive. Therefore, at present, the multidisciplinary framework needed for implementation of such a therapeutic intervention remains in development in Ireland, and therefore outside of specialist hospital-based clinics, these interventions are not widely available.
2. Pharmacotherapy
There are four medications licenced for the treatment of obesity in Ireland: orlistat (Xenical ® ). liraglutide 3 mg (Saxenda ® ), semaglutide 2.4mg (Wegovy ® ), and naltrexone/ bupropion (Mysimba ® ). All four medications have been shown to be effective in producing weight loss greater than placebo for a duration of at least one year.
Orlistat is an inhibitor of pancreatic lipase, and inhibits the digestion of fat. Orlistat does not target appetite or satiety mechanisms but can result in almost 3% weight loss in addition to weight lost via a diet and exercise programme. More than 15% of people using orlistat will lose more than 10% of their body weight.
Liraglutide is a daily, subcutaneously administered, human glucagon-like peptide 1 (GLP-1) analogue that acts centrally to reduce appetite and increase satiety. It results in an average weight loss of more than 6% in addition to weight lost via diet and exercise based regimen. More than 30% of people using Liraglutide lose more than 10% of their body weight.
Semaglutide is a once weekly, subcutaneously administered, GLP-1 analogue that, like Liraglutide, acts centrally to increase satiety and reduce hunger. Using the obesity treatment dose of 2.4mg weekly, average weight loss at one year is in excess of 12% and more than 60% reduce their body weight by 10% (including 50% who lose more than 15% of their body weight).
Naltrexone hydrochloride/ bupropion hydrochloride enhances satiety centrally and modulates the hedonic responses to eating, therefore reducing cravings. This medication can result in over 5% weight loss in addition to weight lost via a diet and exercise programme. More than 15% of people using Naltrexone hydrochloride/bupropion hydrochloride will lose more than 10% of their body weight.
While these obesity treatments are licensed for the treatment of obesity in people with or without diabetes, at the time of writing, they are not covered by the GMS or the drug payment schemes, and so people must fund their treatment out of pocket.
3. Bariatric and Metabolic Surgery
Bariatric and metabolic surgery is the most effective intervention in treating obesity and obesity-associated diabetes. All procedures are performed laparoscopically with a very low rate of complications. In diabetes, surgery is a more effective treatment in treating type 2 diabetes than medical care alone. Surgery improves glycaemic control in the medium-term, but also reduces mortality and maintains control of diabetes in the long-term. Therefore, surgery is increasingly used to primarily treat diabetes rather than the associated obesity.
Weight loss after surgery usually reaches a maximum twelve months post-operatively, with a mean ten-year weight reduction of 25%. The weight loss associated with surgery is durable in general, although weight regain can occur in a minority of surgical recipients. The weight loss occurs in tandem with significant improvements in multiple health outcomes including a reduction in all-cause mortality.
Weight loss after surgery is not a result of physical restriction or calorie malabsorption, as is commonly believed. The major mechanism of weight loss after surgery is increased satiety and decreased hunger, which is associated with changes in gastrointestinal hormones such as GLP-1. There is also evidence that surgery increases energy expenditure, despite reduced food intake. Therefore, surgery directly addresses the two major components of the disease of obesity.
Surgery is the only treatment with evidence for long-term weight loss, and reduction in all cause mortality, and therefore should be considered in all people with obesity. While the peri-operative risks are as low as general elective surgery, these procedures are not ‘the easy option’. Before proceeding a thorough multidisciplinary assessment is needed to ensure candidates are fully prepared to have an optimal response to surgery.
Conclusion
Obesity is a disease that affects all aspects of human health that can result in secondary disease and disability. However, obesity can be successfully treated. The treatment of obesity needs to be individualised, and can include diet, exercise and behavioural interventions, pharmacotherapy, and surgical interventions.
Given that there are treatment options available, people with obesity need to be recognised and offered referral for treatment. As a healthcare system, we need to provide greater access to treatment to every person living with this disease. This year the HSE published a new Model of Care for Obesity. It is hoped that this is the start of a new phase of public sector investment in obesity care that will increase availability of therapy and offer people living with obesity treatment options that will reduce the morbidity and mortality associated with this insidious chronic disease.
References available on request
Written by Therese Coleman, Senior Bariatric Dietician, St Vincent’s Private hospital and Dr Karl Neff, Consultant Endocrinologist, St Vincent’s Healthcare Group
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