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ABC of obesity. Obesity - Time to wake up

  • October 2006
  • The BMJ 333(7569):640-2
DOI:10.1136/bmj.333.7569.640
Authors:
David Haslam at University of Chester
David Haslam
Naveed Sattar at University of Glasgow
Naveed Sattar
Mike Lean
Mike Lean
Mike Lean
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Abstract

The obesity epidemic in the United Kingdom is out of control, and none of the measures being undertaken show signs of halting the problem, let alone reversing the trend. The United States is about 10 years ahead in terms of its obesity problem, and it has an epidemic of type 2 diabetes with obesity levels that are rocketing. Obesity is a global problem—levels are rising all over the world. Moreover, certain ethnic groups seem to be more sensitive than others to the adverse metabolic effects of obesity. For example, high levels of diabetes and related diseases are found in South Asian and Arab populations. Although most of the medical complications and costs of obesity are found in adults, obesity levels are also rising in children in the UK and elsewhere.Prevalence of obesity worldwide. Adapted from Haslam D, James WP. Lancet 2005;366: 1197-209View this table:In this windowIn a new windowDefinition of obesity Limited time to act Obesity can be dealt with using three expensive options: Treat an almost exponential rise in secondary clinical consequences of obesityTreat the underlying obesity in a soaring number of people to prevent secondary clinical complicationsReverse the societal and commercial changes of the past 200 years, which have conspired with our genes to make overweight or obesity more normal. Sheaves of evidence based guidelines give advice on the treatment of all the medical consequences of obesity, and an evidence base for identifying and treating obesity is accumulating. Although the principles of achieving energy balance are known, an evidence base of effective measures for preventing obesity does not exist. The methods of randomised clinical trials are inappropriate, and so some form of continuous improvement methodology is needed. Results from Health Survey for England 2002. The most recent Health Survey for England (2004) states that “Between 1995 and 2001, mean BMI increased among boys (from 17.6 …
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doi:10.1136/bmj.333.7569.640
2006;333;640-642 BMJ
David Haslam, Naveed Sattar and Mike Lean
Obesity—time to wake up
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ABC of obesity
Obesity—time to wake up
David Haslam, Naveed Sattar, Mike Lean
The obesity epidemic in the United Kingdom is out of control,
and none of the measures being undertaken show signs of
halting the problem, let alone reversing the trend. The United
States is about 10 years ahead in terms of its obesity problem,
and it has an epidemic of type 2 diabetes with obesity levels that
are rocketing. Obesity is a global problem
—
levels are rising all
over the world. Moreover, cer tain ethnic groups seem to be
more sensitive than others to the adverse metabolic effects of
obesity. For example, high levels of diabetes and related diseases
are found in South Asian and Arab populations. Although most
of the medical complications and costs of obesity are found in
adults, obesity levels are also rising in children in the UK and
elsewhere.
Limited time to act
Obesity can be dealt with using three expensive options:
x Treat an almost exponential rise in secondary clinical
consequences of obesity
x Treat the underlying obesity in a soaring number of people
to prevent secondary clinical complications
x Reverse the societal and commercial changes of the past 200
years, which have conspired with our genes to make overweight
or obesity more normal.
Sheaves of evidence based guidelines give advice on the
treatment of all the medical consequences of obesity, and an
evidence base for identifying and treating obesity is
accumulating. Although the principles of achieving energy
balance are known, an evidence base of effective measures for
preventing obesity does not exist. The methods of randomised
clinical trials are inappropriate, and so some form of
continuous improvement methodology is needed.
In the United Kingdom, even if preventive measures against
obesity were successful immediately (so that not one more
person became obese) and people who are obese do not gain
weight, there would still be an epidemic of diabetes and its
complications within 10-20 years. This is because so many
young people are already in the clinically “latent” phase of
obesity, before the clinical complications present. Treatment of
obesity must be prioritised alongside prevention. It will take an
unprecedented degree of cooperation between government
departments; schools; food, retail, and advertising industries;
architects and town planners; and other groups to improve our
“toxic” environment. Meanwhile, in their clinics, doctors have to
deal with the obesity epidemic one person at a time
—
a daunting
role.
This is the first article in the series
Proportion obese (%)
0
20
30
Men
10
North America and Cuba
Western Europe
Latin America and the Caribbean
Central and eastern Europe
Middle East
China and Vietnam
South East Asia
Japan, Australia, Pacific Islands
Africa
Age (years)
Proportion obese (%)
5-14 15-29 30-44 45-59 60-69 70-79 ≥80
0
20
30
40
Women
10
Prevalence of obesity worldwide. Adapted from Haslam D, James WP. Lancet
2005;366:1197-209
Year
Prevalence (%)
1995
0
10
15
20
25
30
35
Girls aged 6-10 years
5
1996 1997 1998 1999/2000 2001 2002
Prevalence (%)
0
10
15
20
25
Boys aged 6-10 years
5
Obese Overweight
Results from Health Survey for England 2002. The most recent Health Survey
for England (2004) states that “Between 1995 and 2001, mean BMI increased
among boys (from 17.6 to 18.1) and girls (from 18.0 to 18.4) aged 2-15”
Definition of obesity
x Obesity is excess body fat accumulation with multiple
organ-specific pathological consequences
x Obesity is categorised by body mass index (BMI), which is
calculated by weight (in kilograms) divided by height (in metres)
squared. A BMI > 30 indicates obesity and it is reflected by an
increased waist circumference
x Waist circumference is a better assessor of metabolic risk than BMI
because it is more directly proportional to total body fat and the
amount of metabolically active visceral fat
Practice
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Health consequences
It has been known for centuries that obesity is the cause of
serious chronic disease. Only relatively recently has the full
spectrum of disease linked to obesity become apparent
—
for
example, recognition that most hypertension, previously
considered “essential,” is secondary to obesity. Among
preventable causes of disease and premature death, obesity is
overtaking smoking.
Economic costs
Every year obesity costs the UK economy £3.5bn (€5.1bn,
$6.4bn), and results in 30 000 deaths;18 million days of work
taken off for sickness each year. Strategies for primary care that
encourage primary prevention of chronic disease, including
obesity management, would achieve considerable financial
rewards. The Counterweight study on obesity reduction and
maintenance showed that obese people take up a greater
proportion of time in general practice than non-obese people.
Obese patients also need more referral, and are prescribed
more drugs across all the categories of the British National
Formulary than people of normal weight. Resources are being
spent mainly treating the secondary consequences of obesity.
Preventing obesity is not encouraged. The Counterweight study
also showed that obesity can be managed in a population
without a major increase in resources.
Benefits of managing obesity
Uniquely among chronic diseases, obesity does not need a
scientific breakthrough to be treated successfully. Enough is
known about the causes of obesity and that diet, exercise,
behaviour therapy, drugs, and even laparoscopic surgery can be
effective. The barriers to successful management of obesity are
political and organisational ones, along with a lack of resources.
In the long term, the cheapest and most effective strategy to
improve the health of the population may be to prioritise and
provide incentives for the management of obesity.
The metabolic and vascular benefits of even modest reductions
in weight are well described. Weight loss also enhances fertility
in women, improves respiratory function and mental wellbeing,
reduces risk of cancers and joint disease, and improves quality
of life. Major benefits for individuals from dramatic
interventions, like obesity surgery, have been shown. Optimal
medical treatment can also produce major weight loss for many
patients (outside the constraints of randomised controlled
trials). The most striking benefits, however, in proportional
terms, are from modest weight loss (5-10%), when fat is
particularly lost from intra-abdominal sites. For example, this
amount of weight loss increases life expectancy 3-4 years for
overweight patients with type 2 diabetes, which is impressive.
Obesity management includes priority treatment of risk
factors for cardiovascular disease. The benefits of treatment are
greater for overweight and obese people because their risks are
higher. Primary prevention of obesity and overweight would
prevent much secondary disease. Many people do stay at
normal weight, but there is no proven effective intervention.
Beyond BMI
The most clinically telling physical sign of serious underlying
disease is increased waist circumference, which is linked to
insulin resistance, hypertension, dyslipidaemia, a
proinflammatory state, type 2 diabetes, and coronary heart
Costs attributable to obesity in Scotland in 2003*
Illness
GP contacts Prescribing costs (£)
No Cost (£) Per person Total
Obesity 58 346 758 503 3 2 818 025
Hypertension 988 493 12 850 406 179 43 650 190
Type 2 diabetes 65 777 855 098 409 18 901 220
Angina pectoris 93 178 1 211 309 720 20 348 921
Myocardial
infarction
33 372 433 838 720 14 598 139
Osteoarthritis 37 003 481 045 112 2 240 485
Stroke 5829 75 777 35 106 333
Gallstones 1575 20 470 67 57 448
Colon cancer 2631 34 207 0 0
Ovarian cancer 382 4967 91 6970
Gout 17 321 225 170 25 244 155
Prostate cancer 0 0 2949 162 609
Endometrial
cancer
0 0 168 14 362
Rectal cancer 0 0 1114 12 812
Total 1 303 907 16 950 791 103 161 670
£1 = €1.40 or US$1.8
* Adapted from Walker A. The cost of doing nothing—the economics of obesity in
Scotland. University of Glasgow, 2003 (www.cybermedicalcollege.com/Assets/
Acrobat/Obesitycosts.pdf)
Health consequences of obesity
Greatly increased risk (relative risk >3)
x Diabetes
x Hypertension
x Dyslipidaemia
x Breathlessness
x Sleep apnoea
x Gall bladder disease
Moderately increased risk (relative risk about 2-3)
x Coronary heart disease or heart failure
x Osteoarthritis (knees)
x Hyperuricaemia and gout
x Complications of pregnancy
—
for example, pre-eclampsia
Increased risk (relative r isk about 1-2)
x Cancer (many cancers in men and women)
x Impaired fertility/polycystic ovar y syndrome
x Low back pain
x Increased risk during anaesthesia
x Fetal defects arising from maternal obesity
Estimated metabolic and vascular benefits of 10% weight loss
Blood pressure
x Fall of about 10 mm Hg in systolic and diastolic blood pressure in
hypertensive patients
Diabetes
x Fall of up to 50% in fasting glucose for newly diagnosed patients
People at risk for diabetes, such as those with impaired glucose
tolerance
x > 30% fall in fasting or two hour insulins
x > 30% increase in insulin sensitivity
x 40-60% fall in incidence of diabetes
Lipids
x Fall of 10% in total cholesterol
x Fall of 15% in low density lipoprotein cholesterol
x Fall of 30% in triglycerides
x Rise of 8% in high density lipoprotein cholesterol
Mortality
x > 20% fall in all cause mortality
x > 30% fall in deaths related to diabetes
x > 40% fall in deaths related to obesity
Practice
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disease. More than 250 years ago, Giovanni Battista Morgagni
used surgical dissection to show visceral fat. He linked its
presence to hyper tension, hyperuricaemia, and atherosclerosis.
Jean Vague (in the 1940s and ’50s) and Per Bjorntorp (in the
1980s) led the interest in gender specific body types of android
and gynoid fat distribution. Pear shaped women tend to carry
metabolically less active fat on their hips and thighs. Men
generally have more central fat distribution, giving them an
apple shape when they become obese, although obese women
can have a similar shape.
Cross-sectional studies show that waist to hip ratio is a
strong correlate of other diseases. Prospective studies, however,
show a large waist as the strongest anthropometric predictor of
vascular events and diabetes because it predicts risk
independently of BMI, hip circumference, and other risk factors.
Management of obesity in the UK
Clinical practice in the UK focuses on secondary prevention for
chronic diseases. Obesity is often neglected in evidence based
approaches to managing its consequences. One problem is in
recording the diagnosis.
Computerised medical records and better linking of datasets
will help monitor efforts to reduce obesity locally and
nationally. The UK Counterweight audit showed that height and
weight are measured in about 70% of primary care patients
only. The diagnosis of obesity is rarely recorded in reports from
hospital admissions or outpatient attendance. A survey of
secondary prevention of coronary heart disease shows that,
despite the importance of obesity as a coronary heart disease
risk factor, it is still poorly managed, even in high risk patients.
Although patients with type 2 diabetes are often overweight,
most are managed in primary care and few regularly see a
dietician.
The first revision of the general medical services contract
gives practices eight points for creating registers of obese adults,
but this is only a start in readiness for a more emphatic second
revision of the contract. BMI is seldom measured in people of
normal weight so their progression to becoming overweight is
missed, and with it the opportunity to prevent more than half of
the burden of diabetes in the UK.
Producing a register of obese individuals is futile unless
something is done with the list. Weight management and
measurement of fasting lipid profile, glucose, and blood
pressure should be encouraged. This could be used to identify
people at high risk of cardiovascular disease and diabetes
through risk factors related to obesity, which individually might
fall below treatment thresholds. Without these steps the
contract creates more work with no clinical benefit. The
arguments are strong for awarding points for assessing obese
individuals and offering weight management programmes. The
clinical and economic benefit will be extended if effective
obesity prevention strategies can be developed. These are not
alternative strategies: strategies are needed for both prevention
and treatment with ongoing monitoring and evaluation.
Conclusion
Obesity affects almost every aspect of life and medical practice.
The rise in obesity and its complications threatens to bankr upt
the healthcare system. Early treatment and prevention offer
multiple long term health benefits, and they are the only way
towards a sustainable health service. Doctors in all medical and
surgical specialties can contribute.
Further reading
x Haslam D, James WP. Obesity. Lancet 2005;366:1197-209.
x Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the
prevention of diabetes in obese subjects (XENDOS) study: a
randomized study of orlistat as an adjunct to lifestyle changes for
the prevention of type 2 diabetes in obese patients. Diabetes Care
2004;27:155-61.
x James WP, Astrup A, Finer N, Hilsted J, Kopelman P, Rossner S, et
al. Effect of sibutramine on weight maintenance after weight loss: a
randomized trial. STORM Study Group. Sibutramine Trial of
Obesity Reduction and Maintenance. Lancet 2000;356:2119-25.
x McQuigg M, Brown J, Broom J, Laws RA, Reckless JP, Noble PA, et
al. Counterweight Project Team. Empowering primary care to
tackle the obesity epidemic: the Counterweight Programme. Eur J
Clin Nutr 2005;59:93-100.
x De Bacquer D, De Backer G, Cokkinos D, Keil U, Montaye M, Ostor
E, et al. Overweight and obesity in patients with established
coronary heart disease: are we meeting the challenge? Eur Heart J
2004;25:121-8.
x Scottish Intercollegiate guidelines (www.sign.ac.uk)
x National Institute of Health guidelines (www.nhlbi.nih.gov/
guidelines/obesity/ob_gdlns.htm)
Stereotypical apple (metabolically harmful, more common in men) and pear
(metabolically protective and more common in women) shapes. Making
obesity an object of humour has impeded the understanding of its medical
consequences. Obesity can contribute to musculoskeletal and psychological
problems and have profound effects on quality of life
The figure showing obesity in English girls and boys aged 6-10 uses data
from Health Survey for England 2002 (using criteria of the International
Obesity Task Force for overweight and obesity), and is adapted from
British Medical Association Board of Science. Preventing childhood obesity,
2005 (www.bma.org). The box showing health consequences of obesity is
adapted from International Obesity Taskforce (www.iotf.org/.../slides/
IOTF-slides/sld016.htm). The box showing metabolic and vascular
benefits of 10% weight loss is adapted from Jung RT. Obesity as a disease.
Br Med Bull 1997;53:307-21.
David Haslam is a general practitioner and clinical director of the
National Obesity Forum.
The ABC of obesity is edited by Naveed Sattar
(nsattar@clinmed.gla.ac.uk), professor of metabolic medicine, and
Mike Lean, professor of nutrition, University of Glasgow.
The series will be published as a book by Blackwell Publishing early in
2007.
Competing interests: DH has received honorariums for presentations and
advisory board attendance from Sanofi-Aventis, Abbott, Roche and
GlaxoSmithKline. NS has received fees for consulting and speaking from
Sanofi-Aventis, GlaxoSmithKline, and Merck, and from several companies
in the field of lipid lowering therapy. ML has received personal and
departmental funding from most major pharmaceutical companies
involved in obesity research, and from several food companies. A full list
can be seen on www.food.gov.uk/science/ouradvisors/ACR/
BMJ 2006;333:640–2
Practice
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Full-text available
  • Dec 2022
Objetivou-se analisar o perfil socioeconômico e antropométrico de vaqueiros de um campeonato de vaquejada da cidade de Pacajus-Ce. Foram coletados dados de um total de 28 sujeitos do sexo masculino através de um questionário socioeconômico com 19 questões abertas e fechadas, assim avaliação antropométrica (massa corporal e estatura). Foi demonstrado que a maioria dos vaqueiros (64,3%, n=18) apresentava renda salarial acima da média do trabalho por gênero no estado. Quanto à antropometria verificou-se que 50% (n=14) dos participantes foram classificados como pré-obeso no IMC. Além disso, apesar do estudo não avaliar composição corporal, constatou-se por meio da RCQ a condição de pré-obesidade não era advinda de excesso de massa muscular, uma vez que a maior parte dos vaqueiros, 64,3%, encontrava-se com valores de RCQ em risco elevado de desenvolver doenças cardiovasculares. Por fim, apesar de competidores, os vaqueiros apresentam valores de antropometria inadequados que podem influenciar negativamente na aptidão física.
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Nobiletin Prevents Obesity-Related Complications and Neurological Disorders: An Overview of Preclinical and Clinical Studies
Article
Full-text available
  • Feb 2023
Nobiletin (NOB) chemically known as 5, 6, 7, 8, 3, 4-hexamethoxyflavone is a polymethoxylated flavonoid that is predominantly found in the peel of citrus fruits. Animal studies and a limited number of clinical trials suggest that NOB has multifunctional biological activities such as protection against obesity and obesity related cardiometabolic disorders, neuroprotection, antidiabetic, anticancer, anti-allergy, antioxidant, anti-inflammatory, and free radical scavenging abilities. NOB and its metabolites have also displayed antibacterial and antiviral properties and inhibition of hepatic lipogenesis. This review is intended to discuss the pharmacological actions and therapeutic potential of NOB and its metabolites in the prevention of obesity and obesity associated health complications. Evidence obtained from animal studies and a limited number of clinical trials suggest that NOB may be a promising candidate for the prevention of obesity and obesity related disorders as well as non-communicable diseases. Further studies are needed to understand the mechanism of action of NOB at the cellular, genetic, and molecular levels. Keywords: Nobiletin, obesity, cardiometabolic disorders, inhibition of hepatic lipogenesis, antiatherogenic.
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Diabetes in the Arab World
Chapter
  • Aug 2021
The prevalence of diabetes in the Arab world increased greatly during the past two decades, largely due to adaptation to Western lifestyles and poor dietary choices. Diabetes in the Arab world is estimated to double in 2035. Hereditary risk factors play a key role in the uncontrolled prevalence of diabetes in the Middle East. However, obesity and a lack of exercise cannot be ignored as factors in the swift rise of diabetes in the Arab world. Half of the patients suffering from diabetes are unaware of their condition and are at great risk of diabetic complications; such patients are a large component of the high rates of morbidity and mortality in diabetic patients in the Arab world. The majority of costs associated with diabetes relate to treatments of diabetic complications. Therefore, early treatment in diabetes is important both for health as well as in reducing longterm costs. This chapter discusses the chronic complications of diabetes by dividing them into microvascular and macrovascular diseases, where microvascular complications have a higher prevalence. Microvascular complications involve nephropathy, neuropathy, and retinopathy, while macrovascular complications include stroke, cardiovascular diseases, and peripheral artery diseases. There is an urgent need to fight the spread of diabetes in the Arab world considering the epidemic of diabetes in the region
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(H2O)-H-2 turnover method as a means to detect bias in estimations of intake of nonbreast milk liquids in breast-fed infants
Article
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Firstly, to compare food, and macronutrient intake as obtained from a single 24-h recall and a frequency questionnaire (FQ) covering a 14-day period in breast-fed infants aged 4 months of age. Secondly, nonbreast milk water intake (NB-WI, ml/day) was used as an estimation of energy and macronutrient intake, and NB-WI as calculated from FQ (NB-WIFQ) was compared with NB-WI as measured using the dose-to-the-mother 2H2O turnover method (NB-WIDO) covering the same 14-day period. Cross-sectional. Community-based study in urban Pelotas, Southern Brazil. In all, 67 breast-fed infants aged 4 months of age recruited at birth. (1) Bias in estimations of food and macronutrient intake of the 24-h recall relative to FQ; (2) Bias in NB-WIFQ relative to NB-WIDO. In infants with an energy intakeFQ from complementary foods above the 50th percentile (1.03 kcal/day), estimations of water, tea, juice, and milk intake were not different between 24-h recall and FQ (n=34). Nor were estimations of energy and macronutrient intake (protein, fat, and carbohydrates) different between the two methods, and bias was nonsignificant. NB-WIDO was divided into quintiles and compared with NB-WI(FQ). The first two quintiles included negative values for NB-WIDO as a result of random errors of the 2H2O turnover method. Subsequently, bias of NB-WIFQ relative to NB-WIDO was positive in the 1st (P=0.001) and 2nd quintile (P=0.638), respectively. Bias was negative for the three highest quintiles, and within this group, underestimation by FQ was significant for the 3rd and 4th quintile (-57.4%, P=0.019; -43.7%, P=0.019). Firstly, at the age of 4 months FQ covering a 14-day period provides similar results on food and macronutrient intake as compared to a single 24-h recall for estimations of complementary liquid foods. Secondly, NB-WIFQ appeared to be a good proxy for macronutrient and energy intake in breast-fed infants receiving other liquids. In infants with NB-WIDO>0, the method provides a useful tool for the detection of bias from FQ, and results indicate an underestimation from FQ relative to the 2H2O turnover method. This exercise could be applied wherever the 2H2O turnover method is used in combination with conventional food consumption techniques for measuring intake of nonbreast milk liquids of breast-fed infants in whom solid foods have not yet been introduced. It would help interpreting estimations of macronutrient intake, and could be relevant to studies of dietary intake of infants and its relationship with growth and health.
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Empowering primary care to tackle the obesity epidemic: the Counterweight Programme
Article
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To improve the management of obese adults (18-75 y) in primary care. Cohort study. UK primary care. Obese patients (body mass index > or =30 kg/m(2)) or BMI> or =28 kg/m(2) with obesity-related comorbidities in 80 general practices. The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. Proportion of practices trained and recruiting patients, and weight change at 12 months. By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as 'completers' in that they attended the requisite number of appointments in 3, 6 and 12 months. 'Completers' achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months. The Counterweight programme provides a promising model to improve the management of obesity in primary care.
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Obesity as a disease
Article
  • Feb 1997
Obesity is associated with the development of some of the most prevalent diseases of modern society. The greatest risk is for diabetes mellitus where a body mass index above 35 kg/m2 increases the risk by 93-fold in women and by 42-fold in men. The risk of coronary heart disease is increased 86% by a 20% rise in weight in males, whereas in obese women the risk is increased 3.6-fold. Elevation of blood pressure, hyperlipidaemia and altered haemostatic factors are implicated in this high risk from coronary heart disease. Gallbladder disease is increased 2.7-fold with an enhanced cancer risk especially for colorectal cancer in males and cancer of the endometrium and biliary passages in females. Endocrine changes are associated with metabolic diseases and infertility, and respiratory problems result in sleep apnoea, hypoventilation, arrhythmias and eventual cardiac failure. Obesity is not a social stigma but an actual disease with a major genetic component to its aetiology and a financial cost estimated at $69 billion for the USA alone.
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Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance
Article
  • Dec 2000
Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and to enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 2 years. Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates. 467 (77%) patients with more than 5% weight loss were then randomly assigned 10 mg/day sibutramine (n=352) or placebo (n=115) for a further 18 months. Sibutramine was increased up to 20 mg/day if weight regain occurred. The primary outcome measure was the number of patients at year 2 maintaining at least 80% of the weight lost between baseline and month 6. Secondary outcomes included changes in uric acid concentrations and glycaemic and lipid variables. Analysis was by intention to treat. 148 (42%) individuals in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 sibutramine-treated individuals who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 individuals in the placebo group (odds ratio 4.64, p<0.001). Patients had substantial decreases over the first 6 months with respect to triglycerides, VLDL cholesterol, insulin, C peptide, and uric acid; these changes were sustained in the sibutramine group but not the placebo group. HDL cholesterol concentrations rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p<0.001). 20 (3%) patients were withdrawn because of increases in blood pressure; in the sibutramine group, systolic blood pressure rose from baseline to 2 years by 0.1 mm Hg (SD 12.9), diastolic blood pressure by 2.3 mm Hg (9.4), and pulse rate by 4.1 beats/min (11.9). This individualised management programme achieved weight loss in 77% of obese patients and sustained weight loss in most patients continuing therapy for 2 years. Changes in concentrations of HDL cholesterol, VLDL cholesterol, and triglyceride, but not LDL cholesterol, exceed those expected either from weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease.
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XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients
Article
It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].
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Overweight and obesity in patients with established coronary heart disease: Are we meeting the challenge?
Article
  • Feb 2004
Several epidemiological studies have reported increasing obesity rates in the general population during last decades. We studied the prevalence of overweight and obesity in the high priority group of patients with established coronary heart disease (CHD) and the therapeutic control of manageable coronary risk factors in relation to body mass index. Data from a representative sample of patients having experienced a recent cardiac event before the age of 71 years from 15 European centres participating in the EUROASPIRE II study, were gathered in the period 1999-2000 through standardized methods. In total, 5535 coronary patients with valid height and weight measurements were included. About one in three patients (31%) was diagnosed as obese with additionally half of the patient population being overweight (48%). Obesity was 10% more prevalent among women and significantly less smokers were observed among overweight and obese subjects, twice as many diabetics and more people with low education. Overweight and obese patients had more frequently raised blood pressure and elevated cholesterol after adjustment for age, gender, education, diabetes and centre. In patients using blood pressure lowering agents, 56% of obese and 51% of overweight patients were still having raised blood pressure compared to 42% in normal weight patients. A similar result was observed for the therapeutic control of total cholesterol. Since their hospital discharge, obese and overweight patients did not alter lifestyles regarding fat intake and physical activity. In the period between coronary event and interview, body weight had increased with at least five kilograms in a quarter of all patients. These results suggest that the growing population of overweight and obese coronary patients is at particularly high risk for further cardiovascular complications due to elevated risk factor levels on the one hand and their insufficient therapeuticcontrol on the other hand. Our results also confirm the considerable weight gain seen in a high proportion of patients following their cardiac event.
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Obesity
Article
Excess bodyweight is the sixth most important risk factor contributing to the overall burden of disease worldwide. 1.1 billion adults and 10% of children are now classified as overweight or obese. Average life expectancy is already diminished; the main adverse consequences are cardiovascular disease, type 2 diabetes, and several cancers. The complex pathological processes reflect environmental and genetic interactions, and individuals from disadvantaged communities seem to have greater risks than more affluent individuals partly because of fetal and postnatal imprinting. Obesity, with its array of comorbidities, necessitates careful clinical assessment to identify underlying factors and to allow coherent management. The epidemic reflects progressive secular and age-related decreases in physical activity, together with substantial dietary changes with passive over-consumption of energy despite the neurobiological processes controlling food intake. Effective long-term weight loss depends on permanent changes in dietary quality, energy intake, and activity. Neither the medical management nor the societal preventive challenges are currently being met.
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  • Jan 2005
  • 1197-1209
  • D Haslam
  • W P James
x Haslam D, James WP. Obesity. Lancet 2005;366:1197-209.