educator's guide - xplore health · 2019-01-23 · however, for people of asian origin, ......

BACKGROUND INFORMATION

Educator's guide

“A crisis of fat?”

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A crisis of fat? - 2 - Background information

TABLE OF CONTENTS

1. Introduction 3

2. State of the art 3

2.1. What is obesity 3

2.1.1 How common is obesity and whom does it affect? 4

2.1.2. Is obesity the same as body fat? 6

2.2. Causes of obesity 6

2.2.1 Genes 7

2.2.2 Environment 9

2.2.3 Epigenetics: genes and environment working together 12

2.3. Physiological processes affecting energy balance and weight regulation 13

2.4. Consequences of obesity 16

2.5. Obesity treatment 19

2.5.1 Treatment approaches 19

3. Ethical, Legal and Social Aspects (ELSA) 22

3.1. Introduction 22

3.2. Is Obesity a health problem? 22

3.3. The causes of obesity 23

3.4. Treatment of Obesity 25


1. Introduction

These teacher guidelines will give you information on the Xplore Health module “A crisis of

fat?”. It will first introduce the topic to enable you to prepare your lesson using the different

multimedia tools that you will find on the website. The guidelines provide information on the

state of the art in this research field and on the ethical, legal and social aspects surrounding

this topic.

2. State of the art

A rising prevalence of obesity is seen around the world. Worried about the long-term threat to

health from obesity, doctors and researchers are trying to understand what makes people

become obese so that they can design treatments and prevention strategies.

2.1. What is obesity?

Obesity is a disease characterized by an increase in the percentage of adipose tissue. It is

defined in terms of Body Mass Index (BMI), a simple measurement that takes into account a

person’s height and weight. To calculate BMI (kg/m2), the weight in kilograms is divided by

the square height in metres.

The definitions of overweight and obesity for most people are:

Overweight: BMI greater than or equal to 25kg/m2

Obesity: BMI greater than or equal to 30kg/m2

However, for people of Asian origin, lower cut-offs have been suggested due to their higher

percentage of body fat:

Overweight: BMI greater than or equal to 23kg/m2

Obesity: BMI greater than or equal to 25kg/m2

Defining obesity and overweight in children is harder due to their changing body mass during

growth. Similar growth charts to those that define normal height and weight at different ages

during childhood have been produced to define obesity and overweight in children.


2.1.1 How common is obesity and whom does it affect?

Key facts from WHO on obesity and overweight (fact sheet online, 16 February 2018):

- Worldwide obesity has nearly tripled since 1975.

- In 2016, 1.9 billion adults, 18 years and older, were overweight. Of these, over 650

million were obese.

- 39% of adults, 18 years and older, were overweight in 2016 and 13% were obese.

- Most of the world's population live in countries where overweight and obesity kills

more people than underweight.

- 41 million children under the age of five were overweight or obese in 2016.

- Over 340 million children and adolescents, aged 5-19, were overweight or obese in

2016.

Obesity and overweight are increasing in Spain and across the world. Currently, the OECD

countries with the highest rate of overweight or obese in adulthood include the USA (71%),

Mexico (72.50%), Chile (74.2%), New Zealand (66.6%) and Hungary (62.30%). In Spain,

51.5% of men and women have overweight or obesity. Combined data on obesity and

overweight prevalence show several countries where less than 40% of the adult population

have normal weight.

Figura 1. Rising overweight (including obesity) rates in adults aged 15-74

years [from OECD Obesity Update 2017]


Data on the prevalence of obesity from the World Health Organization (Noncommunicable

Diseases (NCD) Country Profiles, 2018) in adolescents aged 10-19 show that in Spain 11%

of boys and 6% of girls have obesity. These data show that these problems begin as early as

childhood. According to OECD latest Obesity Update 2017, in England, 12.35% of boys and

10.75% of girls aged 3-17 years have obesity; in the United States, these figures are 20.71%

and 18.97%.

Data from countries with rapidly enlarging populations and economies, such as India and

China, show a prevalence of childhood overweight and obesity. In China, 22% of boys and

15% of girls have obesity; these figures are 21% of boys and 18% of girls in India. These

global trends are studied closely by international organisations, such as the World Obesity

Figure 2. Obesity among adults, 2015 or nearest year [from OECD Obesity Update 2017]

https://www.worldobesity.org/


Federation, who describe obesity as a ‘global epidemic’ and are concerned by the negative

impact it is having on health and disease and economic growth. Data on these trends is also

collected on a local level, and collated into health profiles for different regions by the Public

Health Observatories.

2.1.2 Is obesity the same as body fat?

All body fat stores contribute to body mass index; however, research has shown that not all

fat stores have the same impact on a person’s health. Visceral fat describes the fat located

around bodily organs such as the liver, kidneys and heart, and is thought to be metabolically

active and associated with insulin resistance (associated with the development of type 2

diabetes), and high levels of cholesterol. People with excess visceral fat also have an

increased risk of heart disease and stroke.

People with excess visceral fat tend to hold their extra weight around the middle of the body,

causing a so-called ‘apple-shaped’ appearance. This is also sometimes known as central

adiposity or obesity, and can be defined by the ratio of a person’s waist to hip ratio. Men tend

to have more visceral fat and be more centrally obese than pre-menopausal women (who

tend to have more subcutaneous fat and be ‘pear-shaped’). People from different ethnic

groups also have a varying risk of increased visceral fat: people of Asian origin are

particularly at risk, and this may underlie their increased risk of disorders such as type 2

diabetes. The lower BMI cut-offs for overweight and obesity in Asian people is to take into

account these differences.

Body fat is difficult to measure, but can be measured using DEXA (dual energy X-ray

absorptiometry) as well as MRI and CT scans. Bioelectrical impedance analysis is a simple,

non-invasive technique, often performed in pharmacies and gyms, but is rarely accurate.

2.2. Causes of obesity

Obesity is a so-called ‘complex disease’ where it is known that several different factors play a

role in causing the disease. These causes include a person’s environment (e.g. what they

eat, how much exercise they do, their sleep habits, etc.) and their genes. A person’s genes

and environment are thought to work together to predispose someone to obesity.

https://www.worldobesity.org/


2.2.1 Genes

Evidence that a person’s genetic make-up plays a role in their risk of becoming obese comes

from many different types of research study. In their clinics, doctors often see that patients

with overweight and obesity have family members who have the same pattern of bodyweight.

This can often imply a genetic link, but as patterns of eating and exercise often also run in

families, this does not make it easy for researchers to decide whether a family is sharing

similar obesity genes, or whether they are sharing similar ‘obesogenic’ environments.

Studies of twins have helped clear up this uncertainty. Monozygotic (identical) twins share

the same genes but dizygotic twins do not, and neither type of twins has the same

environment. Estimates of how ‘heritable’ obesity is can be calculated from looking at the

intra-pair correlation of weight: monozygotic twins have a higher heritability of weight and

obesity than dizygotic twins, suggesting a genetic influence on weight (see below). Further

evidence of the importance of genetics over environment comes from adoption studies,

where twins and siblings were reared apart, as was sometimes normal practice in the 1940s.

Researchers found that a familial tendency towards obesity was still apparent in twins and

siblings reared separately, suggesting an overriding influence on obesity from genetics,

despite different environments.

Figure 3. Body Mass in twins [Borjeson, Acta Paediatr Scand, 1976]


Finding obesity genes

The last few decades of genetic research have taken many approaches to discover genes

that could cause obesity. These genetic studies have taken two main approaches: (i)

identification of common genetic variants (or single nucleotide polymorphisms) using

genome-wide association studies (GWAS), and (ii) identification of rare gene defects (such

as mutations and deletions) with candidate gene studies. These two approaches highlight the

complexity of understanding genetic factors in obesity as they study two very different

aspects of obesity: the common causes of obesity (using GWAS) and the rare causes of

obesity (using candidate gene studies). Identification of common genetic variants associated

with obesity helps researchers to understand the risk to large numbers of people, but these

variants are only associated with a small increase in risk (e.g. each copy of the FTO risk

allele is associated with a 0.45kg/m2 increase in body mass index). In contrast, identification

of a rare variant may yield insight into some unusual forms of obesity, such as congenital

leptin deficiency, but these are unlikely to be present in the majority of people with obesity.

Many people have questioned whether these recent genetic insights are worth the

considerable financial investment put into them. Understanding common variants may enable

doctors to build up ‘risk profiles’ for patients to help inform them more accurately about their

own genetic risk of developing obesity. It may also be possible to use this genetic information

to tailor treatments and lifestyle interventions that are known to be more or less effective for

certain risk groups according to their genetic make-up. For those people with rare forms of

obesity, understanding the exact gene defect causing their condition may enable them to use

prenatal screening in the future to prevent the same condition being present in offspring.

Single gene defects may also be targeted by gene therapies or specific tailored treatments,

such as the administration of leptin treatment to the few sufferers of congenital leptin

deficiency. For any genetic researcher, the ‘translation’ of their genetic insights to clinical

practice is important to justify their study. Genetic researchers also need to consider the

ethical aspects of their work and the potential for genetic information to be misused.

Type of genetic variation Rare single gene variants Multiple common gene variants

Effect on body weight Account for a lot of extra weight

in very few people

Account for a little bit of extra

weight in a lot of people

Examples Ob gene, MC4R gene FTO gene, TMEM18 gene

Association with other Can be associated with rare One of many ‘normal’ varied


clinical conditions diseases, e.g. congenital leptin

deficiency, MC4R deficiency

human characteristics, but can

also associate with other

common diseases, e.g. type 2

diabetes

How are these found? Candidate gene studies, animal

studies, exome sequencing

Genome-wide association studies

Potential relevance Prenatal genetic testing and

gene therapy

Understanding risk of disease

and tailoring disease prevention

strategies.

2.2.2 Environment

The environment can contribute significantly to a person’s weight, irrespective of their genetic

make-up. The environment is a loose definition that can take into account a range of factors

that affect (a) energy intake, such as the quantity, cost and type of food that is available, their

appetite and behaviour towards food, and (b) energy expenditure, including physical activity

levels and patterns of sedentary behaviour.

In simplistic terms, a balance exists between the energy intake and energy expenditure, such

that if the former exceeds the latter, there will be net weight gain. For an ‘average’ person,

the excess energy intake required to cause weight gain may be as little as 100 calories per

day to cause a 5kg weight gain over a 1-year period. Although calculations such as this help

us to understand how small amounts of excess energy intake can influence a person’s

weight, they do not take into account the range of other factors that affect propensity to

weight gain.

Energy intake Energy expenditure

Food intake Basal metabolic rate (depends on body

stores and contribution from

fat/carbohydrates/protein)

Individual behaviours – hunger and

appetite, habits, comfort, sleep, etc.

Thermogenesis, e.g. from food intake and

muscle activity

Societal and economic influences

e.g. cost and availability of food

Physical activity (e.g. volitional exercise or

normal activities such as sitting, working,

fidgeting, transportation, posture)


Energy intake

Over the last century, improving economic circumstances in developed countries have

enabled the production of cheap, high-energy food that can be transported around the world.

The increased accessibility of calorific food, and a food industry that promotes certain eating

patterns, are thought to underlie the rapid increase in obesity amongst the world’ population

over the last few decades. In contrast, economic difficulties facing the world’s poorest

nations, as well as famine cycles, prevent many populations from suffering the epidemics of

overweight and obesity that much of the global population is experiencing. Migration patterns

of certain ethnic groups highlight the importance of the external environment and

accessibility to food, such as that seen when Asian people move from a rural to urban

settings in Asia, or to a more ‘Westernised’ country such as the UK. The focus on population-

wide influences on energy intake, such as the role of the food industry, is key to prevention

strategies in obesity.

Individual determinants of energy intake are also important to the development of overweight

and obesity. A range of factors influences an individual’s energy intake, and this ranges from

hunger and appetite leading a person to eat, the satiety, satisfaction and comfort derived

from eating (whether as meals or snacks), as well as patterns of habitual eating. The

neurobehavioural mechanisms underlying all of these factors are increasingly understood,

and explain the complex relationship between all of these factors, many of which are

physiologically and genetically regulated.

Energy expenditure

The basal metabolic rate (BMR) of an individual accounts for 60-75% of their daily energy

expenditure. The BMR refers to the amount of energy the body requires to maintain normal

body functions in a normal environment, e.g. homeostatic cellular processes that keep the

body alive. The BMR itself is determined by a person’s body size and composition, and in

particular, their fat-free mass. The fat-free mass of a person is composed of their most

metabolically active tissues, such as the heart, brain, kidneys and liver. Fat, or adipose

tissue, contributes 20-30% of body weight, but only 3-5% of resting metabolic rate. It is

therefore understandable that a person with excessive body fat content is relatively

‘inefficient’ in their overall basal metabolic efficiency, with less calories used to keep their

body fat stores in a metabolic equilibrium. This inefficiency is one reason in which overweight

and obese people find it difficult to lose weight, as they have to increase their energy

expenditure significantly to overcome this net energy surplus.


Thermogenesis, or heat production by the body, is another important determinant of energy

expenditure. The body produces heat in many different contexts: in response to food

consumption, from muscle activity during exercise, during a stress response when hormones

such as adrenaline are produced, and finally in low temperature conditions when the body

shivers to produce heat.

The processes regulating basal metabolic rate and thermogenesis are not voluntary, and

therefore individuals have little ability to change these should they be trying to lose weight.

However, it is hoped that research into these processes may yield some novel methods of

pharmacological treatment for obesity in the future.

Physical activity is a significant component of energy expenditure, and one that is modifiable

through individual behaviour such as exercise. Large studies show the benefits of regular

physical activity on weight and risk of diseases, including type 2 diabetes, cardiovascular

disease, stroke and premature death. Regular, intensive physical activity, and achieving a

negative energy balance can be a successful means to weight loss, and in particular can

result in the loss of abdominal fat. However, an increase in physical activity may be

insufficient for an obese person to achieve significant weight loss; and only when this is

coupled with dietary change may the necessary weight loss ensue. The WHO

recommendations on physical activity (see below) are based on the knowledge that regular

physical activity is required to maintain weight in normal, healthy people. Societal and

behavioural factors play a significant role in activity levels, with increasing car use and

sedentary behaviour, playing an important role in increasing rates of obesity and overweight.

Children, aged 5-17 years Adults, aged 18-64 years Older adults, aged 65 +

Moderate-vigorous physical

activity for at least 60 minutes

per day

150 minutes of moderate intensity

activity (at least 10 minutes at a

time), e.g. 30 minutes 5 days per

week

Any amount of physical activity

that their abilities and conditions

allow will provide health

benefits.

Vigorous intensity activities,

such as those that strengthen

muscle and bone, at least 3

days per week

Or, 75 minutes of vigorous activity

per week

Aim to be active daily, and if

possible, aim for the same

amount of physical activity as

younger adults

Obese adults should aim for 60-

90 minutes of moderate intensity

physical activity on most days.


Moderate physical activity means that you get warm, mildly out-of-breath, and mildly sweaty,

and can include brisk walking, jogging, cycling, swimming, dancing or heavy housework or

DIY. Vigorous physical activity will include more intensive sports that result in being more

out-of-breath, sweaty or an increased heart rate.

2.2.3 Epigenetics: genes and environment working together

Epigenetics is an emerging area of science that is uncovering the link between our genes

and the environment they function in. Humans, mammals, and many other species, have an

epigenetic ‘landscape’ across the genome, composed of a range of different chemical and

structural modifications. This landscape varies according to the genetic architecture, forming

certain patterns in gene promoters, introns, exons and outside of genes. One commonly

studied epigenetic mark, DNA methylation, occurs predominantly at CpG dinucleotides

across the genome and can affect the machinery of gene transcription and whether a gene

gets switched on or off (gene expression). Other epigenetic marks, such as histone

modifications, can affect the structure and function of proteins with wide-ranging downstream

effects. From these descriptions, it can be seen that epigenetic modifications interact with our

genetic make-up very closely. To understand this better, some researchers have used an

analogy of an orchestra conductor (the epigenetic modification) in charge of many musicians

(the DNA code) to create music (gene functioning).

The environment in which an organism lives may also have a significant effect on its

epigenetic profile. In this context, the ‘environment’ of an organism might include certain

nutritional deficiencies, a high calorie food intake, smoking, or exposure to drugs and toxins.

These adverse environmental conditions can directly affect epigenetic marks with

downstream effects on gene expression and resulting in a change in phenotype, such as

onset of disease. Mammalian epigenetic profiles are thought to have particular susceptibility

to changes in environment during development as their epigenetic marks are erased and

replaced when an embryo is formed. This area of research is called ‘fetal programming’, and

describes how the maternal in utero environment may ‘programme’ an individual fetus to

develop obesity and type 2 diabetes in adulthood.

Understanding the role of epigenetic processes in mediating gene-environment interactions

is giving exciting insight into the causes of complex diseases such as obesity and type 2

diabetes. Researchers at the Blizard Institute, Queen Mary University, London (Finer,

Rakyan, Hitman) have identified that the presence of a genetic polymorphism associated

with increased risk of obesity at the FTO gene changes the epigenetic state of that gene


region. A different methylation pattern in the FTO gene in people carrying the obesity risk

allele may affect how the gene works and could provide a route to understand the

mechanisms underlying obesity. Epigenetic changes have also been found in fetal

programming studies such as the Dutch Winter Hunger Study that identifies higher rates of

type 2 diabetes in the adult offspring who were born to famine-exposed mothers during the

1940s. Another study has shown that mothers in India who are deficient in vitamin B12 (due

to the lacto-vegetarian diet that many Hindu Indians follow) have children who are at

increased risk of obesity and type 2 diabetes by the age of 6 years. These findings are

thought to underlie the concept of the ‘thrifty’ phenotype, in which there is an adaptation

towards an environment of nutritional deprivation, set down in early life. Other researchers

think that there may also be a ‘thrifty’ genotype in populations that have evolved to cope with

nutritional deprivation. It is thought that the ‘mismatch’ between these thrifty developmental

origins, and an actual environment of nutritional excess in later life, may be a high-risk

situation for individuals to become obese and develop type 2 diabetes. Many researchers

have suggested that this theory may explain the recent Asian epidemic of obesity and type 2

diabetes as populations have changed rapidly over recent generations from living in rural

areas (with nutritional deprivation and high physical activity levels) to urban areas where food

is in excess and physical activity levels drop.

2.3. Physiological processes affecting energy balance and weight regulation

As described above, obesity comprises a complex clinical condition, with numerous

underlying genetic and environmental triggers. These influences are now understood to

affect a wide range of physiological processes in the regulation of overall energy balance.

Such processes include neurobehavioral pathways and gut-brain signalling pathways that

work together to achieve homeostasis in the body. An expanding knowledge of these

complex pathways is yielding significant insights into the factors that control body weight,

such as appetite, satiety and eating behaviours.

The homeostatic control of energy balance (and therefore body weight) requires the brain to

act as the chief regulator, coordinating metabolic signals from peripheral tissues, paracrine

and endocrine hormone signalling, and feedback from the nervous system.

Metabolic signals, e.g. glucose and free fatty acids

Ingestion of food and the peripheral metabolic processes in the body is central to the

production and utilisation of fuel for energy metabolism. Variation in levels of these


metabolites, such as after a meal, will set off a cascade of peripheral metabolic processes

designed to achieve homeostasis. These processes include glycogenolysis (obtainment of

glucose from the degradation of glycogen), glycolysis (breakdown of glucose to extract

energy for cellular processes) and glycogenesis (conversion of excess glucose to glycogen

for storage). Like glucose, free fatty acids (from circulating trigylcerides) provide a rapid

energy source for metabolism and cellular processes (from storage in adipose tissue) and

can readily turn into fuel stores. These metabolic signals, as well as others, are the trigger to

more complex signalling within the body that not only keeps body systems working efficiently,

but also is responsive to states of energy influx, or extra requirement. The signalling that is

required comes from a combination of processes, driven mainly by hormonal and nervous

systems.

Hormonal signals

These function on both a local (paracrine) and systemic (endocrine) level, and include

numerous peptide hormones with wide-ranging effects. Leptin is one such important

hormone, produced peripherally by adipose cells according to the current size of fat stores in

the body. It is the main message to the brain, via other circulating hormones such as insulin,

on what is happening in the peripheries of the body and therefore how the brain should

regulate overall energy balance (e.g. to try and achieve a negative energy balance if fat

stores are excessive). On the other hand, there is Adiponectin, a hormone whose levels are

inversely proportional to the BMI, which, among other effects, increases insulin sensitivity

and promotes the uptake of glucose. It is thought that abnormalities in this process of leptin,

adiponectin and insulin signalling may predispose an individual to obesity and may offer a

therapeutic target in the future. Other important signalling hormones include gut peptides,

such as glucagon-like peptide 1 (GLP1) and cholecystekinin (CCK). These peptide hormones

are produced in the gastrointestinal tract in response to food ingestion, and provide an

efficient and responsive feedback system to other hormones to regulate the metabolic

environment (e.g. via insulin to normalise post-meal glucose levels) and to the brain to

control appetite and induce a feeling of fullness after a meal. In obesity and type 2 diabetes,

this efficient gut peptide response to a meal can be blunted, and newer drug therapies are

designed to restore the efficient functioning of this system. Other important hormone

regulators of energy balance include the more commonly-known hormones produced in

response to hypothalamic-pituitary signalling to peripheral endocrine organs such as the

adrenal gland (corticosteroids and sex hormones) and thyroid gland (thyroxine) as well as

the production of growth hormone by the pituitary itself. These endocrine hormones can


affect the basal metabolic rate (e.g. thyroid and sex hormones), insulin sensitivity

(corticosteroids), fat mass (growth hormone) as well as providing a complex interaction

between many of the circulating metabolic signals and paracrine signals already discussed.

Nervous system signals

The autonomic nervous system, which includes both sympathetic and parasympathetic

nerves, carries homeostatic feedback signals to and from the brain from peripheral tissues in

the body in relation to energy balance. Peripheral effects of these neural stimuli include the

production of insulin and catecholamines (e.g. adrenaline and noradrenaline) that in turn

regulate peripheral processes of energy balance. The vagus nerve carries important nerve

signals back to the brain from mechanoreceptors in the stomach in response to their being

stretched by ingestion of a meal.

Within the brain, several important structures receive the feedback signals outlined above

and provide a responsive signal back to the peripheries. The key neuroanatomical regions

are in the hypothalamus and brainstem, and importantly, these areas lack an effective blood-

brain-barrier, allowing easy recognition of signalling molecules and metabolites in the

systemic circulation. Within these brain regions, several specific neuropeptides communicate

and coordinate the complex messaging that is required to achieve optimal energy balance.

Important neuropeptides include neuropeptide-Y (NPY), which stimulates food intake and

decreases energy expenditure, the alpha-melanocyte stimulating hormone (a-MSH),

responsible for suppressing food intake, amines (e.g. serotonin, acetylcholine, adrenaline,

noradrenaline) and amino acids (e.g. glutamate and GABA).

In addition to the hypothalamus and brainstem, other brain regions are emerging as

important players in subtle neurobehavioral responses to food, such as reward behaviours,

motivation, and the hedonistic aspects of food intake. These brain regions include the

nucleus accumbens, and amygdala and contain many dopaminergic neurons. These brain

regions interact closely with the cortical function of the brain, including that of taste and visual

recognition of food, and a conscious understanding of food, appetite and hunger.

Understanding the complexities of these neurobehavioral mechanisms, and their relationship

to the homeostatic control of energy balance is crucial to develop a deeper understanding of

obesity. At the present time, many researchers are studying these brain processes to try to

understand whether in some people they malfunction and predispose to obesity. Animal

models, and studies of humans with rare monogenic forms of obesity is providing significant


insights, and this is being applied to larger studies of obesity to see if they may have a role in

common obesity. It is hoped that a detailed understanding of this pathophysiology will result

in targeted therapies that treat the higher control of food intake and appetite.

2.4. Consequences of obesity

Obesity and overweight predispose to a number of related ‘metabolic’ disorders that can

increase a person’s risk of morbidity and mortality. The risk of death is increased in people

with obesity mainly due to the excess risk of cardiovascular disease and cancer. Even when

adjusting for overall activity levels, smoking and other relevant factors, obesity is known to be

an independent risk factor for premature death.

Obesity-related complications relate to the complex pathophysiological problems associated

the disorder, and are wide-ranging. In relation to the obesity itself, the onset of these

complications is often silent or delayed, but provides an important focus for intervention as

they underlie the morbidity and mortality of obesity.

Figure 4. Estimated Hazard Ratios for Death

from Any Cause According to Body-Mass Index

for All Study Participants and for Healthy

Subjects Who Never Smoked [from A.

Berrington, P. Hartgede, J.R. Cerhan, et al.

(2010) Body-Mass Index and Mortality among

1.46 Million White Adults. The New England

Journal of Medicine 363;23, 2211-2219]


Mechanisms Associated risk

Metabolic disorders

Type 2 diabetes

High cholesterol and

triglycerides

(dyslipidaemia)

Fatty liver disease

Polycystic ovarian

syndrome

Adipocytes in excessive visceral fat stores

are large and produce excessive amounts

of pro-inflammatory cytokines, such as IL-1,

IL-6 and TNF-alpha. Suppression of

adiponectin production reduces the body’s

sensitivity to insulin. The overall result of

these factors is to increase insulin

resistance, one of the main features of type

2 diabetes.

An increase in free fatty acids passing

through the portal venous circulation also

results in excessive production of certain

lipid particles (e.g. VLDL) that further

increases the production of insulin into the

systemic circulation, compounding the

effects of peripheral insulin resistance.

Chronically high levels of insulin (due to

insulin resistance), as well as changes to

sex hormone metabolism can result in

polycystic ovarian syndrome, which is

manifest by chronic anovulation and raised

androgen concentrations.

Individuals with a BMI of

25-29.9 are twice as likely

to develop type 2

diabetes, and for a BMI of

30 or greater, the risk is

sixfold.

Cardiovascular disease

Hypertension

Ischaemic heart

disease

Strokes

Adipocytes produce hormones, such as

angiotensinogen, that can increase blood

pressure by direct effects on the vascular

endothelium. Obese people also have a

raised total circulating blood volume and

this raises the viscosity (thickness) of blood

as well as increasing its clotting ability (via

production of pro-thrombotic factors). These

factors all increase the risk of hypertension,

but also play a role in the development of

atherosclerosis. The dyslipidaemia

associated with obesity also predisposes to

the development of atherosclerosis, a

product of the accumulation of lipids in the

vascular endothelium. When this

The risk of high blood

pressure is 5 times higher

in people who are obese.



pathological process affects coronary

arteries, it can result in angina and heart

attacks; in the cerebrovascular circulation, it

results in TIAs and strokes.

Cancer

e.g breast, colon,

endometrial, kidney,

prostate, oesophageal

cancers

The excess risk of cancer in people who

are obese is thought to be due to many

different factors, including the pro-

inflammatory state, changes in metabolism

of sex hormones, and insulin resistance.

At least 10% of cancer

deaths are thought to be

due to obesity

Bone and joint disease

arthritis

osteoporosis

disability

Increased mechanical stress on joints from

excessive body weight can cause arthritis.

Arthritis is common in obesity, and is often

manifest as back pain, knee and hip

problems, and chronic disability. Reduced

bone density can also occur, due to vitamin

D deficiency and higher bone turnover due

to sex steroid hormone imbalance.

Reduced bone density, or osteoporosis,

can lead to fractures and further disability.

Respiratory disease

obstructive sleep

apnoea

obesity

hypoventilation

syndrome

These disorders result from the restriction

to breathing function due to excessive body

fat, fatty tissue in the neck and nasal polyps

obstructing the upper airways, and

hypothalamic disturbance of breathing

patterns.

Psychological problems

depression

anxiety

Mood disturbances, such as depression

and anxiety, are more common in people

with obesity. This is thought to be due to a

range of factors, including behavioural

disturbances associated with trying to lose

weight, dissatisfaction with body image, and

social stigma.

Women in the US who are

obese have a 37%

increased risk of

depression.

Pregnancy

complications

Obesity in pregnancy is increasingly

common due to the increased prevalence of

obesity in young people. Obesity in



pregnancy puts both mother and baby at

risk, due to higher rates of gestational

diabetes, pre-eclampsia and fetal

macrosomia.

2.5. Obesity treatment

The benefits of weight loss in obesity and overweight people are significant. The

Counterweight Programme has estimated that for an obese person with a BMI of >32.5

kg/m2, the benefits of 10% weight loss include a 9-fold decrease in type 2 diabetes, 6-fold

decrease in dyslipidaemia and hypertension and a 4-fold reduction in cardiovascular disease.

The question is how to achieve this weight loss. The view held by many to just “eat less and

exercise more” is correct in that these are the best strategies to achieve a negative energy

balance, but is overly simplistic. The neurobehavioral mechanisms in energy regulation and

the knowledge that individuals with a high fat mass are ‘energy inefficient’, highlights the

complexity of the underlying pathophysiological processes in obesity that are difficult to

overcome to achieve weight loss.

2.5.1 Treatment approaches

Lifestyle intervention, including diet and exercise

Many studies show the effectiveness of lifestyle interventions in both the prevention and

treatment of obesity. Lifestyle interventions can include a range of different approaches, but

their cornerstone is to achieve a negative energy balance through dietary change and

increased physical activity. For those people who are able to adopt significant lifestyle

changes and maintain them in the long-term, the effects on obesity and the development of

obesity-related complications also last into the long-term. In contrast, ‘quick fix’ interventions

such as crash diets, whilst they may achieve short-term weight loss, rarely produce medium-

or long-term effects on body weight. An understanding of the neurobehavioral mechanisms

that control energy balance, as well as the role of higher brain functions, such as reward

behaviour and motivation, that can malfunction in obesity give an insight into why a ‘lifestyle

approach’ to achieving weight loss is difficult.


Drug treatments

Over recent years, several different drug therapies have been trialled and used in the

treatment of obesity. Large clinical trials of some drugs have shown the beneficial effects on

weight loss from drugs such as sibutramine and rimonabant that work mostly centrally on

appetite and energy regulation. However, with increasing use in obese populations, side

effects of these drugs became apparent, including an increase in cardiovascular risk with

sibutramine, or mood disturbance and suicide with rimonabant, and have led to the

withdrawal of both of these drugs. Pharmaceutical companies are continuing to work on

these types of compounds, trying to exploit their potential benefits in newer drugs without the

associated risk of side effects. The mainstay of drug therapy at the present time is orlistat, a

drug that inhibits pancreatic and gastric lipases, preventing the breakdown of triglycerides in

the gut and therefore reducing their absorption and contribution to energy intake. The

benefits of this drug are modest, achieving on average 2-3kg of weight loss over a 1-year

period of taking the drug. However, the concern raised by many patients who take this drug

is that it causes gastro-intestinal side effects due to the rapid passage of high fat foods

through the GI tract, resulting in flatulence and diarrhoea. These side effects stop many

people from taking the drug, but for those who can tolerate them, the drug can be helpful in

the management of obesity.

Newer drug therapies available to treat obesity and type 2 diabetes include the GLP-1

agonists, such as liraglutide and exenetide, which stimulate the action of insulin and promote

weight loss. This drugs work on gut peptide, signalling cascade that is blunted in type 2

diabetes and obesity. As described earlier, these gut peptides, such as GLP-1, are

responsive to food intake in the stomach, producing a cascade of effects to metabolise

glucose and signal to the brain to reduce further food intake and appetite. The drugs used in

this category mimic the natural GLP-1 response in normal individuals. These drugs are

relatively new, and their mechanisms of action are not fully understood, but they seem to be

effective in producing modest weight loss as well as diabetes control over 1 year. Longer-

term studies to test their efficacy in maintaining this weight loss as well as reducing obesity-

related complications are awaited. Furthermore, these long-term follow-up studies will also

provide vital information about their safety and incidence of side effects.

Bariatric (weight-loss) surgery

Currently, bariatric surgery is the most successful means to achieve significant and long-term

weight loss in obese individuals and prevent or treat obesity-related complications. Several


different surgical approaches exist, including gastric banding and bypass operations. These

operations are thought to induce weight loss through a variety of different means, including

the restriction of food into the stomach, promoting early satiety and reduced appetite, as well

as malabsorption from the gut and therefore reduced energy intake. Large studies show that

these operations, and especially gastric bypass, can achieve significant weight loss of 10-

30%, as well as a significant reduction in mortality of up to 40%. These beneficial effects are

thought to outweigh the potential risks of performing surgery in obese individuals, and

studies also show that these operations are highly cost-effective as they reduce the expense

associated with long-term treatment of obesity-related complications such as disability and

type 2 diabetes. At the present time, surgery is an option for individuals with a BMI

>40kg/m2, or >35kg/m2 if associated with obesity-related complications such as type 2

diabetes or obstructive sleep apnoea. In the UK, these criteria are suggested by the National

Institute of Clinical Excellence, based on extensive research and evaluation of their cost-

effectiveness, however on a local level, access to these operations is sometimes restricted

due to short-term budgetary concerns of local health care organisations.

Psychological therapies

The neurobehavioral processes underlying obesity, including systems that promote ‘reward’

and ‘motivation’ from eating can be targeted through specific psychological techniques such

as cognitive-behavioural therapy. This treatment approach can also be useful due to the high

rates of psychological problems, such as depression and anxiety, in people with obesity.

Most specialist obesity services offer tailored psychological support and treatment for

patients. In children with obesity, such approaches often include family-based interventions,

understanding that the tendency towards obesity may be driven by familial eating patterns

and behaviours at home.

Novel therapies

Newer drug therapies are hoped to provide safe and effective non-surgical treatments for

obesity, and this is an area of rapid development by pharmaceutical companies. With

increasing understanding of the pathophysiology of obesity, new therapeutic targets are

suggested, such as those that work on gut-brain signalling pathways and the more complex

behavioural aspects of food intake.


3. Ethical, Legal and Social Aspects (ELSA)

In this section you will find a number of opinions and incentives for discussion in class on

ethical, legal and social aspects (ELSA) related to “A crisis of fat?”:

3.1. Introduction

Obesity is a growing problem for global health, both in the developed world and in newly

industrialising countries. How we think about, and tackle, obesity will have a significant

impact on rates of diabetes, heart disease, joint problems, and many other health conditions.

Obesity is a complex social and medical problem, and public and professional attitudes to

obesity contribute to this complexity.

3.2. Is obesity a health problem?

One initial reaction to the public health challenge of obesity is to argue that overweight or

obesity are not health problems, except in the most extreme cases. Many people who would

be considered clinically obese do not consider themselves to be overweight (and many

people who are not clinically obese consider themselves to be overweight – not simply

people who suffer from anorexia nervosa or bulimia, but people who are in the normal range

of “body-consciousness”).

A commonsense view sees variation in human body size as to be expected, and thus normal

rather than pathological. This is not to say that body size does not attract judgement and

comment – it does. Societies have complex cultural attitudes to body size to do with how

people understand beauty, fitness, and care over personal appearance, signals of prosperity

and so on.

One of the most difficult challenges for health promotion is how to educate people about

what, from a clinical point of view, obesity is (which may not match the commonsense

perception of being “heavy” or “fat” or “big-boned” or, for babies, “bonny”), without trading on

or exaggerating the stigma which attaches to some forms of obesity. Attitudes to obesity are

linked quite strongly to social expectations and comparisons with near neighbours and family

members: someone is not likely to consider themselves as overweight if they see themselves

as typical of their own family and friendship network.

Apart from the extreme cases, people do not often experience obesity directly, or, in the

short term, experience health problems caused by obesity. Even where they do, they may


consider shortness of breath, for instance, as just a sign that they are not very fit, and this

may not bother them, or indeed be a source of humour. In most cases, the consequences of

obesity materialise over time, and people are either unaware of them, or discount their

importance rather heavily. Therefore, while tackling obesity is important both for population

health and for individual health, it can be hard to persuade people of this, without appearing

to be moralistic or bullying. By the time a serious health consequence of obesity has

materialised, it may be too late to do much more than control the symptoms and repair the

damage as best may be.

3.3. The causes of obesity

Personal behaviour

One of the challenges of obesity from a health promotion point of view is that once the

person has accepted that obesity may be a health problem in general, and that it may be (or

become) one for them personally, lay theories of the causes of obesity come into focus.

People’s understanding of the behaviours which lead to obesity, or which can control or

move away from obesity, are complex, and may rest on mistaken or partial understandings

about eating patterns, the nutritional contents of different kinds of food, the amount of food

that constitutes a healthy intake, the efficacy of dieting in different ways, the role of exercise,

and so on. In addition to their “health beliefs”, it is also well known that changing old habits

and acquiring new ones is hard, and the “cognitive biases” which make changing present

behaviour to achieve long term but remote benefits are deeply entrenched in human

psychology.

On the other hand, it is also evident that there is a difference between how we judge our own

behaviour and how we judge that of others. While some of the time we might be more

forgiving or tolerant of others behaviour, much of the time we are all too willing to believe that

others’ behaviours are due to idleness, greed, fecklessness, or lack of willpower, whereas

our own behaviours are either rational, sensible and indeed no one’s business but our own or

hard to change because of “real” difficulties which are “genuine” barriers to behaviour change

(unlike those faced by the idle, feckless, etc. other person who is just weak-willed).

Nowhere is this inconsistency in thinking about behaviour more obvious than in debates

about personal responsibility for ill health (or obesity as a precursor to ill health). Because

obesity is often attributed to moral failings like greed or irresponsibility, a common view is

that the obese person should not receive the same level of help and support than someone


whose diabetes or heart disease is caused by some factor we are more willing to consider

independent of personal conduct. And even within obesity, someone whose overweight is

attributed to a “hormone problem” may receive more sympathy than someone whose

overweight is attributed to a lack of self-control.

Not only do these debates influence the public attitude to treatment of obesity itself, they are

even more influential in debates about the treatment of the health consequences of obesity

(heart disease, diabetes and so on) where a persistent theme seems to be that “self-

incurred” health problems should be a lower priority than “no-fault” health problems.

Genetics and physiology

From the ethical point of view, the main issue raised by the genetics and physiology of

obesity is in informing public attitudes to obesity and the perceived contribution of personal

behaviour. The genetics and physiology of obesity are intricate, and there is not likely to be a

simple genetic test, or set of tests, which could act as a screening test for the risk of obesity,

or obesity-related illness.

The main contribution of genetics and physiology to the clinical medicine of obesity is likely to

be in understanding causal pathways which can lead to medical treatments (considered

below). To the extent that genetics and physiology provide a partial explanation of why some

people are obese, and others are not, these partial explanations fit into the debates we have

just reviewed about the role of personal responsibility. In many ways, these will simply be

new versions of the older explanations of the type “I am not fat, I just have an underactive

thyroid” (meaning – I am overweight, but it’s not my fault) or “My family are all big-boned”

(meaning, I am overweight, but I was born this way, this is my natural shape).

Structural explanations

Although the personal behaviour and personal responsibility accounts of obesity are probably

dominant, there has been a growing interest in public debates about food in the ethics of the

food industry, and in the role of the government in shaping the environment.

The role of the food industry has increasingly been criticised. Concerns are raised about the

content of low quality fat and high energy density products along with the salt and sugar

content of common foodstuffs; while the added salt content of processed foods has long

been a concern, recent interest has broadened to encompass concern about the added

sugar content of processed foods. Not only are consumers unaware of the salt and sugar


contents of what they eat (notwithstanding more explicit food labelling), they are also

unaware of the way salt and sugar influence the desire to eat more of the same, thus

inducing over-eating.

Criticism has been levelled at portion sizes in fast-food outlets, at the marketing of high-

energy foods to children (including in some countries sponsorship of school activities and

sporting events to underscore an apparent link between consumption of high-energy foods

with active lifestyles), and so on. Either incomplete or misleading information, and pro-

consumption “nudges” which increase consumption and divert from healthier options are

increasingly widely criticised.

Another problem concerns the way food is retailed; while the widespread availability of

supermarkets and chains of small shops has made a big difference to the convenience of

urban life and in many rural communities as well, the marketing practices of the chains have

been criticised for undermining the diversity of products available, presenting relatively

unhealthy (high fat, high energy processed foods) in more convenient and lower cost forms

than fresh foods, and the discounting of bulk purchases in ways that induce higher rates of

consumption (notoriously in the case of alcohol, but also for sweets and biscuits, carbonated

drinks, and so on). If the marketing practices and dominant market position of the highstreet

retailers make healthy eating more difficult and more expensive, then there is a clear case for

government intervention through fiscal policy, product regulation, and licensing, as well as

the currently popular “nudges”, “responsibility deals” and voluntary agreements with the food

industry.

3.4. Treatment of obesity

The main approaches to obesity include education and information; behaviour change;

medication; and surgery.

Education and information involve identifying (possibly through screening programmes, more

likely through discussion at routine medical appointments, and possibly through referral to

specialist weight-loss services) people who are obese or at risk of becoming obese, and

educating them about the dangers of obesity and about what can be done to overcome

obesity.

This educational approach has certain hazards: it can enhance stigma; it may focus more on

the “worried well” than on the “genuinely” obese; it may not translate into actual behaviour


change. However, most governments and health services are now taking a more active

approach to raising public and individual awareness of the problems of, and caused by,

obesity.

Mere education and information alone may influence some people to change their behaviour

by taking up more intense physical activity, dieting, and deliberate attempts to eat a more

varied diet or a diet that has a higher proportion of fresh foods or lower fat or lower energy

content. However, many people will require further advice or assistance. Some private sector

initiatives, such as “Weightwatchers”-style programmes seem to have some success, and

public sector initiatives involving “prescriptions for exercise”, cognitive behaviour therapy,

and other means have also been tried with some success. Unfortunately, the evidence base

for interventions to reduce obesity involving personal behaviour change is not particularly

reliable, and further controlled trials are certainly needed.

Another strategy for personal behaviour change, involving “nudges” which “change the

defaults” for personal behaviour without needing direct and deliberate action on the part of

the consumer him or herself, is also receiving a lot of attention now. Some critics of this style

of intervention worry that because “nudges” do not involve autonomous choice they are

unfair or manipulative. However, the natural response to that is to point to the widespread

use of these types of behaviour modifying strategy by supermarkets and other retailers in

encouraging people to buy more, or certain kinds of, products already. To harness these

techniques to promote health would at least (a) have some chance of success and (b)

advance a personally and publicly beneficial, rather than a purely commercial, goal.

A different set of criticisms looks at the activity patterns of modern life, which encourage

sedentary work and long-distance commuting in cars or vehicles, which do not involve

exercise (but may involve boredom and boredom-induced comfort eating and drinking). The

role of government in providing open spaces for exercise (especially in schools, but for the

community at large) and in regulating transportation to make cycling and walking easier,

safer and more attractive, is important, and increasingly recognised.

All of these structural issues are currently the topic of much discussion in the West. However

it is clear that they are now, and will continue to be, just as important in the newly

industrialising countries, which are beginning to go through the “demographic transition”, and

where regulation of the food and drinks industries may be limited or only nascent.


Medical Treatment

Over the years, many different medical treatment strategies have been tried to treat obesity

directly, or to modify behaviour. Medicines, which boost the consumption of energy by the

body (such as amphetamines), were popular at one time. There was a vogue for appetite

suppressants. Recent approaches, which involve persuading the brain that the stomach is

full, when a smaller amount of food has actually been consumed, have been heavily invested

in by the pharmaceutical industry. So too have drugs which inhibit the uptake of fats or

energy from food consumed.

Aside from the medical question of how far these drug-based approaches are successful in

practice, and what side effects they have, the ethical questions here are challenging. First, it

is questionable whether a medical treatment, which permits the consumer to eat large

amounts of food without putting on weight, is morally acceptable: it may encourage waste or

greed, and it entrenches a high consumption habit, which will probably persist once the

medical treatment is discontinued. Second, there is a challenge along the lines that it is

morally preferable to change one’s behaviour through one’s own efforts, rather than through

taking a pill.

This type of criticism is of long-standing; similar debates arise in psychiatry about the relative

ethical standing of drug-based treatments for depression or low mood and cognitive

behavioural or psychotherapeutic interventions. It might reasonably be argued that where

someone cannot successfully change their diet or activity patterns, then a pill might be just

the intervention they need. And it may also be that the pill gets them started and makes

behaviour change easier, and thus more sustainable. Outside careful clinical trials we are

simply speculating and moralising.

Surgical treatment

In extreme cases, surgery to reduce the digestive tract so as to reduce appetite and the

ability to consume large quantities of food and drink has a good track record. But it is unlikely

to be a useful tool in large scale public health, dealing with mild to moderate obesity. In

addition, it has to overcome public scepticism about how far obesity is the fault of the obese

person. A standard complaint that surgery for obesity is a poor use of public (or insurance)

money has more to do with the view that the obese person is at fault than it has to do with


objective evidence about cost-effectiveness of the surgery, or the relative ineffectiveness of

other interventions in the most obese patient.

Authors:

The State of the Art document was drafted by Sarah Finer, Specialist Registrar & Clinical

Research Fellow in Diabetes & Endocrinology, Queen Mary University, London. The ELSA

document was drafted by Richard Ashcroft, Professor of Bioethics at Queen Mary,

University of London.


AUTHORS OF THIS DOCUMENT:

Sarah Finer i Richard Ashcroft

TEACHING CONSULTANTS:

Cristina Andrés-Lacueva, Rosina Malagrida i Josep Carreras

COORDINATION:

Rosina Malagrida

DATA: 26 d'octubre de 2018

DEVELOPED BY:

UPDATED BY:

educator's guide - xplore health · 2019-01-23 · however, for people of asian origin, ......

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