Stay Aware!

Diabetes and
Cardiovascular Disease:
Time to Act
The mission of the IDF is to work with our member associations to enhance the lives
of people with diabetes.

© International Diabetes Federation, 2001
No part of this publication may be reproduced or transmitted in any form or by any means
without the prior written permission of the IDF Executive Office.
This and other IDF publications are available from:
International Diabetes Federation
Executive Office
1 rue Defacqz
B-1000 Brussels
Belgium
Tel: +32 2 5385511
Fax: +32 2 5385114
e-mail: idf@idf.org
http://www.idf.org
ISBN: 2-930229-15-2

Acknowledgements
The International Diabetes Federation (IDF) would like to thank
Merck, Sharp & Dohme (MSD), USA, for its generous support in making the publication
of Diabetes and Cardiovascular Disease:Time to Act possible.
IDF also gratefully acknowledges the contribution of the members of
the Diabetes and Cardiovascular Disease Editorial Committee:
Clive Cockram (Chair)
George Alberti
Bjørnar Allgot
Abdullah Al Nakhi
Pablo Aschner
Terrence Dwyer
Steve Haffner
Jean-Claude Mbanya
Cara McLaughlin
Viswanathan Mohan
Corby Shugars
Kelly Stoddard
Special thanks also to Kristen Hynes from the Menzies Research Centre, Australia, for
her help with the mortality figures in Chapter 2.
Editor and project manager: Cara McLaughlin
Project coordinator: Stefania Sella
Project support for mortality data: Lala Rabemananjara
Design and layout: perplex | Aalst, Belgium
Printing: Imprimerie L Vanmelle SA, Gent/Mariakerke, Belgium

Diabetes and Cardiovascular Disease:Time to Act
I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N
[ 5 ]
ContentsPreface:A Time Bomb 7
Introduction 9
Executive Summary 11
Chapter 1: Diabetes 13
Classification 13
Risk Factors 14
The Extent of the Problem 14
Future Outlook 16
Chapter 2: Cardiovascular Disease 19
The Cardiovascular Disease Triad 19
Chapter 3: Diabetes and Cardiovascular Disease: Double Jeopardy 37
A Costly Situation 37
How does Diabetes Lead to Cardiovascular Disease? 37
The Cardiovascular Disease Triad in Diabetes 40
The Vicious Cycle 43
Chapter 4: Risk Factors 45
What is a Risk Factor? 45
Cardiovascular Risk Factors 45
Diabetes and Other High Blood Glucose Conditions:A Major Risk Factor 46
Conclusion 51
Chapter 5: Reducing the Risks 53
Management of Risk Factors in the General Population 53
Management of Risk Factors in People with Cardiovascular Disease 55
Management of Risk Factors in People with Diabetes 55
National Approaches to Prevention: Lifestyle 57
Chapter 6:Treatment of Cardiovascular Disease in Diabetes 59
Treatment of Coronary Heart Disease 59
Treatment of Cerebrovascular Disease 60
Treatment of Peripheral Vascular Disease 60
Conclusion 60
Conclusion:The Way Forward 61
Fact File 63
Contents

[ 6 ]
Annex 1: Diagnostic Criteria for Diabetes and its Risk States 65
Annex 2: Diabetes Prevalence 66
Annex 3: Coronary Heart Disease and Cerebrovascular Disease Mortality Rates 68
Annex 4: Studies of Diabetes and Heart Disease 77
Glossary 81
Bibliography 87

[ 7 ]
ATime Bomb
ATime BombP R E F A C E
D
iabetes is closely associated with cardiovascular disease and therefore an increased risk of
heart attack, stroke and amputation of the lower limbs. Indeed, heart attack and stroke are
the major causes of premature death in people with diabetes. With the rising tide of
diabetes around the globe, the double jeopardy of diabetes and cardiovascular disease is set to
result in an explosion of these and other cardiovascular complications - unless preventive action is
taken now.
Such action includes striving to prevent diabetes itself and, when diabetes is present, to prevent or
delay cardiovascular risk factors in people with the condition. Both these objectives can be
achieved by common strategies, such as promoting healthy lifestyles, educating healthcare
professionals and raising public awareness. What is more, these steps can also help prevent the
onset of cardiovascular disease in the general population.
All should pay heed – policy makers, the healthcare team and, above all, the public. We truly hope
that you take the messages spelt out in this publication to heart. IDF considers cardiovascular
disease to be one of the most serious problems facing people with diabetes, and intends to lead
the fight against it from the front.This is just the beginning!
Professor Sir George Alberti
IDF President

[ 9 ]
Introduction
Introduction
Aims of the Book
is the most up-to-date report on global
cardiovascular disease and diabetes.The
objectives of this publication are to raise
awareness of the close link between these two
diseases and to recommend courses of action
to prevent or delay the cardiovascular
complications of diabetes.
Who Is It for?
This publication seeks to inform healthcare
decision makers of the huge public health
burden posed by cardiovascular disease in
people with diabetes, and to point to the
possibilities of and urgent need for prevention.
IDF’s member associations are encouraged to
make use of this book to lobby their
governments for investment in preventive
strategies.
can also be used as a tool for sensitizing
healthcare professionals to the need for an
aggressive management of all cardiovascular
risk factors in people with diabetes.
This publication is also a source of background
information for member associations’ public
awareness campaigns (the theme of World
Diabetes Day 2001 being ‘Reducing the Burden:
Diabetes and Cardiovascular Disease’).
Finally, anyone with an interest in learning more
about diabetes and/or cardiovascular disease
can consult this publication.
How Should this Book Be Used?
Chapter 1 sets the scene by giving some
background information on diabetes. More
detailed information about diabetes can be
found in other IDF publications such as
Diabetes Atlas 2000 and Diabetes Slide Show.
Chapter 2 defines cardiovascular disease and
discusses its various clinical manifestations.
It also provides the most recent global
mortality data for coronary heart disease
and cerebrovascular disease.
Chapter 3 looks at cardiovascular disease in
the setting of diabetes. For those reading
this as a stand-alone chapter, there are
cross-references to Chapter 2 for
background explanations of the clinical
manifestations of cardiovascular disease.
Chapter 4 examines the risk factors for
cardiovascular disease. It focuses on
diabetes as one of the major cardiovascular
risk factors.
Chapter 5 describes how cardiovascular risk
factors can be managed, both in the general
population and in people with diabetes.
Again, to put the information in context for
those reading this as a stand-alone chapter,
there are cross-references to Chapter 4.
Chapter 6 reviews the treatment possibilities
for established cardiovascular disease in
people with diabetes.
Readers who are unfamiliar with the medical
terminology can make use of the glossary.
Terms included in the glossary are printed in
bold when first used in the text.
The studies of diabetes and heart disease
which are referred to in the text are explained
in more depth in Annex 4.The first reference
to each of these studies is printed in italics.
The research on which Diabetes and
Cardiovascular Disease:Time to Act is based is
documented in the bibliography.

[ 11 ]
Executive Summary
Executive Summary
Diabetes
Diabetes mellitus is a chronic disease which
has been described as a state of raised blood
glucose associated with premature mortality. It
arises when the pancreas fails to produce
enough insulin (type 1 diabetes), or when the
body cannot effectively make use of the insulin
produced (type 2 diabetes).
Diabetes is fast becoming a world pandemic.
Although there is no evidence that type 1
diabetes is preventable, it is clear that
modifiable factors exist for type 2 diabetes. If
action is not taken to stem the tide of type 2
diabetes, the prospects for world health are
bleak.
Cardiovascular Disease
Cardiovascular diseases are diseases affecting
the heart and circulatory system, which, for
example, can result in heart attack, stroke and
amputation of the lower limbs.
Cardiovascular disease is a major worldwide
public health problem. It is the number one
cause of death in industrialized countries. It is
also set to overtake infectious diseases as the
most common cause of death in many parts of
the less developed world, with levels becoming
comparable to those in Western societies – a
situation which seemed inconceivable a few
decades ago.
Diabetes and Cardiovascular
Disease: Double Jeopardy
Diabetes can lead to cardiovascular damage in
a number of ways.The processes do not
develop independently, as each may accelerate
or worsen the others.Thus, as diabetes
progresses, the heart and blood vessels are
exposed to multiple attacks.The cardiovascular
complications of diabetes are therefore a major
cause of illness, death and healthcare costs.
Cardiovascular death rates are either high or
appear to be climbing in countries where
diabetes is prevalent.When we consider that
the number of people with diabetes around the
world is predicted to double over the coming
decades, the outlook for cardiovascular disease
becomes even more alarming.The recent
decline in cardiovascular disease in the USA,
Australasia and western Europe may be
compromised significantly by this upsurge in
diabetes. In other parts of the world where
cardiovascular disease has been proliferating in
recent years, the additional impact of diabetes
threatens to have devastating consequences.
In short, the predicted escalation in diabetes
prevalence is likely to contribute to a
cardiovascular disease epidemic, particularly in
the developing world - unless preventive
measures are taken as a matter of urgency.
Risk Factors
Because of the soaring prevalence of diabetes
worldwide, it now rivals smoking, high blood
pressure and lipid disorders as a major risk
factor for cardiovascular disease. Diabetes also
belongs to a special risk category as it so
markedly increases the risk of cardiovascular
disease.
People with diabetes have a higher prevalence
of many of the other common cardiovascular
risk factors than the general population.What

[ 12 ]
is more, most of these cardiovascular risk
factors have a more harmful effect in the
presence of diabetes.
Many people with diabetes have numerous risk
factors.This fact becomes even more serious
considering that the presence of several risk
factors has a multiplicative and not just an
additive effect.
Due to the higher prevalence and impact of
cardiovascular risk factors, as well as the role
of hyperglycaemia, people with diabetes
without overt cardiovascular complications
merit an intervention against risk factors which
is as aggressive as that which would normally
be provided for individuals with established
cardiovascular disease.
Reducing the Risks
Many cardiovascular deaths are potentially
preventable in both people with and without
diabetes if we can systematically address
known risk factors.While some risk factors are
fixed (such as age, gender and genetic
background), many others are modifiable, such
as high blood pressure, lipid abnormalities,
obesity and smoking.
As many people with diabetes who experience
a first coronary event die prior to getting to
hospital, they cannot benefit from secondary
prevention strategies.Therefore the
management of risk factors in people with
diabetes should precede the onset of
The cardiovascular risk factors specific to
diabetes have been identified by many recent
studies and it has been proven possible to
reduce their impact dramatically.These positive
results call for aggressive action to be taken to
treat the risk factors that are common in
people with diabetes. However such
approaches are frequently not implemented in
clinical practice.There is therefore a clear need
for greater awareness of treatment possibilities
among healthcare professionals.
Lifestyle modification (including healthy eating
habits, regular physical exercise, smoking
cessation and sustained weight loss in the
overweight) can be of major benefit in
preventing non-communicable diseases such as
diabetes and cardiovascular disease. On the
national level, cardiovascular disease prevention
in people with diabetes should in the first place
be part of a comprehensive approach to
prevention in the whole community. It is
inevitably easier for people with diabetes to
change lifestyle behaviour if this is occurring in
the population at large.
Treatment
Many of the treatment methods for
cardiovascular disease are similar irrespective
of whether diabetes is present or not.
However specific issues related to diabetes
include the difficulty of diagnosing ‘silent’
cardiovascular disease, the need for the
aggressive management of all risk factors, and
the use of insulin therapy to achieve blood
glucose control when a heart attack occurs.
Since there are many risk factors involved, the
treatment and follow-up of cardiovascular
disease in people with diabetes can be a
complicated, time-consuming and expensive
process. Hence the value of preventive
measures cannot be overemphasized.
The Way Forward
The good news is that it is possible to slow or
stop the consequences of cardiovascular
disease in diabetes. Action must be taken on
four levels – prevention, treatment, education
and research.There can be no doubt that now
is the time to act.

[ 13 ]
DiabetesDiabetes mellitus is a chronic disease which
has been described as a state of raised blood
glucose (hyperglycaemia) associated with
premature mortality. It arises when the beta
cells in the pancreas fail to produce enough
of the hormone insulin, or when the body
cannot effectively use the insulin produced.
Pancreas
Kidneys
Stomach
Figure 1:The pancreas
Failure of insulin secretion, action or both leads
to raised blood glucose and other metabolic
changes which, if uncontrolled, can cause
serious complications.The most important of
these are retinopathy (affecting the eyes),
nephropathy (affecting the kidneys),
neuropathy (affecting the nerves) and
cardiovascular disease (affecting the
circulatory system).
Classification
One problem over the years has been the
classification of diabetes into different
categories. Most recently, a World Health
Organization (WHO) Consultation and the
American Diabetes Association (ADA) Expert
Committee have divided diabetes into four
main types (Table 1).
What was previously known as insulin-
dependent diabetes mellitus (IDDM) has
become type 1 diabetes under this new
DiabetesC H A P T E R 1
1 Type 1 diabetes • Insulin required for survival due to a lack of insulin
produced by the body as a result of beta cell destruction.
2 Type 2 diabetes • Characterised by disorders of both insulin action or
secretion, either of which may predominate, but both of
which are usually present. Usually controlled by diet,
exercise and oral hypoglycaemic agents. Insulin may be
required for metabolic control.
3 Other specific types of diabetes • Other types of diabetes where the cause is known (eg
genetic defects in beta cell function or insulin action,
diseases of the pancreas, certain other hormonal disorders,
or drug induced disorders).
4 Gestational diabetes • Diabetes appearing for the first time in pregnancy.
Table 1:The four main types of diabetes

[ 14 ]
classification, and non-insulin-dependent
diabetes mellitus (NIDDM) is now type 2
diabetes.
At present the diagnosis of type 2 diabetes is
one of exclusion, that is, it is not one of the
other types.There are undoubtedly many
different causes with a lot of as yet unknown
genes involved.As we find out more about
these, movement of people from the ‘type 2’
category into the ‘other specific types’
category will occur.
Lesser degrees of abnormal glucose levels are
also recognized.These include impaired
glucose tolerance (IGT), blood levels that
are higher than normal but below the level of
someone with diabetes, and impaired fasting
glycaemia (IFG), raised fasting levels of
glucose. IGT is now considered a risk category
rather than a type of diabetes per se, and IFG
is a new risk category. Both IGT and IFG
represent a risk of 25% to 50% of developing
diabetes in the next 10 years, but are
particularly amenable to lifestyle interventions.
The other major offshoot of the new
classification is the metabolic syndrome.
This reflects the clustering of type 2 diabetes
or IGT with several other major cardiovascular
disease risk factors, such as central obesity,
abnormal levels of lipids (dyslipidaemia), high
blood pressure (hypertension), insulin
resistance and a slightly increased output of
protein in the urine (microalbuminuria).
• Central obesity
• Dyslipidaemia
• Hypertension
• Impaired glucose regulation or
diabetes
• Insulin resistance
• Microalbuminuria
Table 2: Components of the metabolic syndrome
Diagnostic criteria for diabetes and its risk
states are provided in Annex 1.
Risk Factors
No clear-cut modifiable risk factors have been
identified for type 1 diabetes.The risk factors
for type 2 diabetes are shown in Table 3.
Certain ethnic groups seem particularly
susceptible to the development of diabetes.
Examples include Amerindians, Pacific island
communities, South Asians, Australian
aborigines, African-Americans and Hispanics.
There is also a strong association with age and
family history. For instance, it has been
estimated that if you have a sibling or parent
with type 2 diabetes, you have a 40% lifetime
risk of developing it yourself.These risk factors
cannot be altered. However, most of the recent
upsurge in diabetes is lifestyle related.The
dramatic rise in prevalence is closely associated
with a lack of physical activity, obesity
(particularly central obesity) and a change to
‘Western’-style diets.These changes, together
with urbanization and mechanization, appear to
be inevitable accompaniments of
modernization.
• Age
• Ethnicity
• Family history
• Obesity (particularly central)
• Physical inactivity
• Urbanization and mechanization
• Westernized diet
Table 3: Risk factors for type 2 diabetes
The Extent of the Problem
Diabetes is becoming a world pandemic. Both
type 1 and type 2 diabetes are spreading
rapidly across the globe (Figure 2).Type 1
diabetes accounts for less than 10% of the total
and is a particular problem in young northern
Europeans. It should be stressed however that
it can occur at any age, and that there are as
many people in the world with type 1 diabetes
over the age of 20 years as there are under the
age of 20.
METABOLIC
SYNDROME
RISKFACTORS

[ 15 ]
Figure 2: Prevalence estimates of diabetes mellitus, IDF Regions, 2000
Source: International Diabetes Federation (2000)
Nodata
2.0%–4.99%
<2%
5.0%–7.99%
8.0%–10.99%
11.0%–13.99%
≥14.0%

[ 16 ]
Type 2 diabetes, which accounts for about 90%
of all cases, is recording the most growth,
particularly in rapidly developing countries. It is
estimated that there
are at least 150
million people in the
world with diabetes
now.This figure is
expected to double
over the next 25
years.The predicted
increase is most
striking in India and
China, but no part of
the world is spared. In
addition to these alarming absolute rises in
numbers, there is also a worsening trend for
the disease to affect younger age groups. In
developed countries the sharpest increases
affect the over 65s, unlike the situation in
developing countries where most new cases
are occurring in those between 44 and 65
years of age. In all parts of the world type 2
diabetes is also now emerging in children and
adolescents, thereby raising the threat of onset
of all complications at an earlier age.
Future Outlook
Although there is no evidence that type 1
diabetes is preventable, it is clear that
modifiable factors exist for type 2 diabetes. If
action is not taken to stem the tide of type 2
diabetes, the outlook for world health is bleak.
Already diabetes consumes up to 10% of
Estimated diabetes prevalence (%)
0 3 6 9 12 15 18
Tonga
Czech Republic
Pakistan
Aruba
Barbados
Trinidad and Tobago
Mexico
Bahrain
Dominica, Commonwealth of
Papua New Guinea1
2
3
4
5
6
7
8
9
10
Mauritius
Bermuda
BritishVirgin Islands
Grenada
St Kitts and Nevis
Hong Kong SAR, PRC
Cayman Islands
Table 4:‘Top ten’ countries for diabetes prevalence
It is estimated that
there are some
150 million people
in the world with
diabetes now.This
figure is expected to
double over the next
25 years.
Fact

[ 17 ]
national health resources in many countries.
Can the pandemic be prevented? The answer is
yes – but only with a high degree of dedication
and commitment. Experimental studies in
China,Tanzania, Finland and Sweden have
proven that lifestyle modification can slow the
development of diabetes in high-risk groups.
But a concerted world effort spearheaded by
WHO, IDF and its national associations is
needed to bring the message home. Put as
simply as possible, the message to be
transmitted is:‘Eat Less,Walk More’.

[ 19 ]
Cardiovascular DiseaseCardiovascular diseases are diseases affecting
the heart and circulatory system. In developing
countries the most common cause of
cardiovascular disease used to be infection of
the heart valves. However, in recent years there
has been a shift away from infectious causes in
many developing nations.Today the most
widespread form of cardiovascular disease
around the world is that which starts with
damage to the blood vessels.
The two main processes by which the blood
vessels become damaged are atherosclerosis
and hypertension:
1. Atherosclerosis leads to the formation of
plaques of atheroma which narrow the
diameter of the large and medium-sized
arteries.This narrowing of the arteries
impairs blood flow. Plaques are also prone
to rupture or to ulcerate and then act as a
site for blood clot formation.The resulting
blood clots, which can block the affected
vessel completely, are usually responsible for
the more severe clinical manifestations of
cardiovascular disease such as heart
attack and stroke.
2. Hypertension damages the smaller vessels in
the circulatory system. Over time they
become scarred, hardened, narrowed and
less elastic. Hypertension can also both
predispose to and accelerate the
development of atherosclerosis.
The Cardiovascular DiseaseTriad
The major clinical manifestations of
cardiovascular disease can be divided into
three groups:
• those affecting the heart and coronary
circulation (coronary heart disease);
• those affecting the brain and cerebral
circulation (cerebrovascular disease); and
• those affecting the lower limbs (peripheral
vascular disease).
Lower limbs
(peripheral
vascular disease)
Brain and cerebral circulation
(cerebrovascular disease)
Heart and
coronary
circulation
(coronary
heart
disease)
Figure 3:The cardiovascular disease triad
Cardiovascular DiseaseC H A P T E R 2

[ 20 ]
Coronary Heart Disease
The heart receives a blood supply of its own
from the blood vessels known as the
coronary arteries.The principal
manifestations of coronary heart disease
include the chronic form resulting from the
narrowing of the coronary arteries - angina -
or the acute forms resulting from the blocking
of the coronary arteries - heart attack or
sudden death. Heart failure is a likely
accompaniment of coronary heart disease in
either the short or long term.
Left
coronary
artery
Aorta
Right
coronary
artery
Figure 4:The heart
Angina:This term is used to describe pain in the
chest due to a reduced blood supply to the
heart (ischaemia). It results from
atherosclerosis in the coronary circulation.
Typically angina causes central chest pain, which
often radiates to the left arm, shoulder or jaw.
The pain is related to exertion and is relieved
by rest. Shortness of breath and sweating are
commonly associated with angina. If the
responsible plaque of atheroma is causing a
severe narrowing of the vessel, then angina
symptoms may rapidly worsen and occur at
rest, and may warn of an impending heart
attack.
Heart attack: Atherosclerosis can lead to a
heart attack if the coronary arteries become
blocked.The onset of a heart attack is usually
heralded by severe central chest pain, which
may also radiate to the left arm, shoulder or
jaw. Severe shortness of breath, sweating and
feeling faint are common additional symptoms.
Sudden death: Sudden death can occur as a
consequence of an abrupt loss of the heart’s
ability to pump blood. It may result from a
massive heart attack or a severe abnormality of
the rhythm of the heartbeat.
Heart failure: This occurs when damage to the
heart muscle is severe enough to prevent it
functioning adequately as a pump. It manifests
itself either acutely with severe shortness of
breath or, more chronically, with shortness of
breath, reduced exercise tolerance and swelling
of the ankles.
Cerebrovascular Disease
The brain receives its blood supply from four
main arteries: the two carotid arteries and
the two vertebral arteries.The clinical
consequences of vascular disease in the
cerebral circulation will depend upon which
vessels or combinations of vessels are involved.
Coronary heart disease Cerebrovascular disease Peripheral vascular disease
• Angina • Stroke • Gangrene
• Heart attack • Transient ischaemic • Intermittent
• Sudden death • attack claudication
• Heart failure • Dementia
Table 5:The major clinical manifestations of cardiovascular disease
CLINICAL
MANIFES-
TATIONS

[ 21 ]
Vertebral
artery
Carotid
artery
Figure 5:The brain
The following situations can occur:
Stroke: Stroke occurs when the blood supply to
a part of the brain is blocked resulting in the
death of an area within the brain. If a large
vessel is blocked the outcome may be rapidly
fatal or may lead to very severe disability. If
smaller blood vessels are blocked the outcome
is less critical and recovery may be good.The
most common types of disability are the loss of
use of one side of the body and speech
problems.
There are three principal types of stroke:
• Thrombotic: Stroke due to the blockage of
an artery leading to or in the brain by a
blood clot.
• Haemorrhagic: Stroke due to bleeding from
a ruptured blood vessel, usually a
consequence of hypertension.
• Embolic: Stroke due to the formation of a
blood clot in a vessel away from the brain.
The clot is carried in the bloodstream until
it lodges in an artery leading to or in the
brain.
The thrombotic and haemorrhagic forms are
the most common, although they occur with
varying frequency in different parts of the
globe.
Transient ischaemic attack:Transient ischaemic
attacks arise when the blood supply to a part
of the brain is temporarily interrupted without
producing permanent damage. By definition,
recovery occurs within 24 hours.These attacks,
particularly if frequent, can be a warning sign of
an impending stroke.They usually result from
small blood clots or clumps from plaques of
atheroma which get carried into the blood
circulation producing transient blockages.
Occasionally these clots may get carried from
the heart or arteries leading to the brain (eg
carotid arteries), rather than from within the
cerebral circulation itself.
Dementia: This may result from repeated
episodes of small strokes which produce
progressive damage to the brain over a period
of time.The main clinical feature of dementia is
a gradual loss of memory and intellectual
capacity. Loss of motor function in the limbs
and incontinence can also occur.
Peripheral Vascular Disease
The lower limbs each receive their blood
supply via an artery known as the femoral
artery. Peripheral vascular disease is said to be
present when the blood vessels in this part of
the body are affected by atherosclerosis. In the
absence of diabetes the single most important
risk factor is heavy cigarette smoking.
Femoral
artery
Figure 6: Lower limbs

[ 22 ]
The following situations can occur:
Gangrene:The term gangrene is used to
describe the death of tissue due to a loss of
blood supply. Severe gangrene can occur as a
result of the blockage of a large blood vessel.
Intermittent claudication:This term describes
pain, usually in the calves when walking, and is
due to an impaired blood supply to the calf
muscles.As with angina, the pain is usually
relieved by resting, but if the situation worsens
pain at rest can also occur.
Cardiovascular disease is a major worldwide
public health problem. It is the number one
cause of death in
industrialized countries.
It is also set to
overtake infectious
diseases as the most
common cause of
death in many parts of
the less developed
world, with levels
becoming comparable
to those in Western
societies – a situation
which seemed
inconceivable a few
decades ago.
The manifestations
vary between different
ethnic groups. For example, while Caucasian
people are particularly prone to disease of the
coronary circulation, Chinese, Japanese and
African people are more prone to disease of
the cerebral circulation. Studies among migrant
populations, such as Japanese people living in
the USA, suggest that these differences may be
due more to variations in external risk factors
such as diet than to differences in the genes of
the people themselves.
Data on the incidence of coronary heart
disease are now available for many developed
countries through the WHO-sponsored
MONICA Project, but unfortunately such data
are not available for developing nations.
Consequently, to obtain an idea of the global
distribution of the disease it is necessary to
examine the available mortality data.
The data in Tables 6 and 7 and Figures 7 to 14
reflect the most recent mortality rates for
coronary heart disease. However substantial
changes have taken place over time. In some
developed nations where rates were extremely
high by world standards - including the US,
many western European countries and
Australasia - mortality has plunged by as much
as 50% in the last 30 years. In other developed
countries where rates were low, such as Japan,
the mortality has remained low. In others,
particularly in eastern Europe, rates have been
climbing. In many developing nations,
particularly in the Pacific and the Middle East,
rates have risen to those previously found only
in the West. On the whole, these trends reflect
changes in the prevalence of the risk factors
(see Chapter 4). For example, there has been a
decline in cholesterol levels in the US and
other previously high-risk countries such as
Finland. Population-based levels of treatment
for hypertension and a decrease in smoking
prevalence have also occurred in many of the
countries which have witnessed a reduction in
coronary heart disease mortality.Availability of
treatment for established disease has also
improved.
The data in Tables 8 and 9 and Figures 7 to 14
provide information on cerebrovascular disease
mortality from all types of stroke. It is
necessary to use mortality data for
international comparisons because, as with
coronary heart disease, incidence data are
available for too few countries.
Cardiovascular
disease is the
number one cause
of death in
industrialized
countries. It is also
set to overtake
infectious diseases
as the most
common cause of
death in many parts
of the developing
world.
Fact

[ 23 ]
Mortality (per 100,000 population per year)
0 100 200 300 400 500 600 700 800
Ukraine
Lithuania
Moldova, Republic of*
Belarus*
Estonia
Kazakhstan Republic
Azerbaijan Republic
Turkmenistan*
Russia
Latvia*1
2
3
4
5
6
7
8
9
10
0 100 200 300 400 500 600 700 800
Ukraine
Trinidad and Tobago
Latvia*
Belarus*
Russia
Kazakhstan Republic
Azerbaijan Republic
Uzbekistan*
Turkmenistan*
Moldova, Republic of*1
2
3
4
5
6
7
8
9
10
Table 6:‘Top ten’ countries for coronary heart disease in males
Table 7:‘Top ten’ countries for coronary heart disease in females
Cerebrovascular disease mortality has also
declined markedly in many developed countries
during the last half of the twentieth century. In
developing countries and in the former Soviet
Union, rates appear to have shot up.They are
certainly much higher in many developing
countries now than in developed countries.
However historical data are lacking to confirm
these trends.
As well as a difference in total trends, there are
also differences in the relative frequencies of
the type of stroke (see page 21) in different
parts of the world. In Japan and China for

[ 24 ]
0 100 200 300 400 500 600 700 800
Yugoslavia*
Kazakhstan Republic
Romania
Bulgaria
Latvia*
Guyana
Russia
Kyrgyz Republic
Ukraine1
2
3
4
5
6
7
8
9
10
0 100 200 300 400 500 600 700 800
Guyana
St Lucia*
Romania
Kazakhstan Republic
Yugoslavia*
Russia
Kyrgyz Republic
Ukraine1
2
3
4
5
6
7
8
9
10
American Samoa*
Table 8:‘Top ten’ countries for cerebrovascular disease in males
Table 9:‘Top ten’ countries for cerebrovascular disease in females
example the haemorrhagic form accounts for a
higher proportion of cases than is seen in the
West.The relative frequency of the thrombotic
form of stroke appears to mirror the
prevalence of coronary heart disease. However,
reliable data on the worldwide occurrence of
each type of stroke are not available.
Data on peripheral vascular disease prevalence
outside the context of diabetes are scarce. It is
therefore currently not possible to provide
international comparisons of the kind prepared
for coronary heart disease and cerebrovascular
disease.

[ 25 ]
Sources and Methodology
Tables 6 to 9, Figures 7 to 14 and Annex 3
provide information on coronary heart disease
and cerebrovascular disease mortality in
selected countries.The data are the latest
obtainable for each country.They were
compiled for Diabetes and Cardiovascular
Disease:Time to Act by the WHO Collaborating
Centre at the Menzies Research Centre,
University of Tasmania, Australia.
The source of data for all countries (except
American Samoa, Canada, Cook Islands, Fiji,
Northern Mariana Islands, Palau,Taiwan, and
Tanzania) was the Global Cardiovascular
Infobase website (http://cvdinfobase.ic.gc.ca/)
of the WHO Collaborating Centre in Ottawa,
Canada.This website uses data from the World
Health Statistics Annual, World Health
Organization, Geneva (1985, 1987, 1988, 1989,
1990, 1991, 1992, 1993, 1994, 1995 and 1996
editions).
• Data for American Samoa were provided by
the Medical Records Office, LBJ Medical
Center (the ‘Causes of Death’ report which
extracts data from death certificates from
the Department of Health’s Office of Vital
Records).
• Data for Canada came from the Health
Statistics Division, Statistics Canada 1999.
• Data for the Cook Islands were provided by
the Medical Records Unit of the Ministry of
Health.
• Data for Fiji were provided by the Ministry
of Health and Social Welfare’s mortality
database which draws on two sources:
medical certificates (Cause of Death) and
Consolidated Monthly Return.
• Data for the Northern Mariana Islands were
provided by the Office of Health and
Planning Statistics of the Department of
Public Health (data from death certificates).
• Data for Palau were provided by the
Department of Health’s Vital Statistics
Database which contains data from the
death registry.
• Data for Taiwan were from the Department
of Health’s Office of Statistics.
• Data for Tanzania were extracted from:
Walker RW, et al (2000).
All data have been age-standardized across the
age range of 35-74 years using the world
standard population.Age-standardization was
calculated from data available on the Global
Cardiovascular Infobase website in January
2001, with the following exceptions:
• Age-standardized rates for ages 35-74 for
American Samoa (coronary heart disease),
Fiji (coronary heart disease and
cerebrovascular disease) and Northern
Mariana Islands (coronary heart disease and
cerebrovascular disease) are estimations
calculated using rates for ages 35-64
published in Profile of Cardiovascular Diseases,
Diabetes Mellitus and Associated Risk Factors
in the Western Pacific Region. Menzies
Research Centre and World Health
Organization Regional Office for the
Western Pacific, 1999.
• Age-standardized rates for ages 35-74 for
Brazil (coronary heart disease and
cerebrovascular disease) were estimated
using the age-standardized rates for ages
35-64 calculated using data from the Global
Cardiovascular Infobase website.
Note: Coronary heart disease for the Cook
Islands consists of heart attack only (acute
myocardial infarction; International
Classification of Diseases code ICD9: 270 Basic
Tabulation List).
The data have been organized according to the
seven IDF Regions:Africa, Eastern
Mediterranean and Middle East, Europe, North
America, South and Central America, South
East Asia and Western Pacific. Data are not
available for all IDF member countries.
Countries marked with an asterisk are not IDF
members.
Estimations of diabetes prevalence (20-79 age
group) are also provided in Annex 2 and below
the charts in Figures 7 to 14 where available.
These data come from: International Diabetes
Federation (2000).
– = No data available.

[ 26 ]
Figure 7: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes
prevalence
25
12
– –
Botswana*
121
160
90
56
Seychelles*
88 85 83
41
South Africa
56
39
616
Zimbabwe
80 73
21 30
São Tomé and Príncipe*
171
142
–
Tanzania
–
–
–
4.0%
1.0%
–
0.9%
male (per 100,000 population/year)
female (per 100,000 population/year)
Cerebrovascular disease mortality
Coronary heart disease mortality
prevalence (%)
Estimated diabetes prevalence
0.0
Africa

[ 27 ]
prevalence
35
22
111
353
Kuwait49
3524
62
Egypt
38
17
121
205
Bahrain
9.3%
7.0%
14.8%
prevalence (%)
0.0
Eastern Mediterranean and Middle East

[ 28 ]
prevalence
prevalence (%)
0.0
Belgium
52
35
138
43
France
41
22
89
22
Hungary
213
118
436
159
Greece
78
58
166
49
Germany
61
39
215
72
Italy
60
38
141
39
65
49
370
127
Ireland, Republic of
65
40
221
74
Austria
110
71
114
33
Albania
Croatia
178
122
235
87
154
95
431
158
Czech Republic
3.2%
4.0%
7.1%
5.3%
5.0%
5.9%
6.6%
3.8%
4.2%4.1%
11.7%
Europe (1)

[ 29 ]
Finland
76
47
316
86
Israel
57
39
177
79
Estonia
232
147
616
205
228
162
602
230
Belarus*
Bulgaria
283
166
317
119
Kazakhstan Republic
276
195
625
256
218
155
426
202
Georgia, Republic of
168
125
638
291
Azerbaijan Republic
Latvia*
291
176
745
228
359
244
427
204
Kyrgyz Republic
4.1%
7.2%
3.7%
–
7.3%
1.4%
–
–
4.5%
5.5%
135 124
448
205
Armenia*
–

[ 30 ]
prevalence
64
47
232
113
Malta
53 48
153
45
Luxembourg
55
36
245
74
Norway
48
35
178
58
Netherlands
147
84
117
42
Portugal
56
32
91
31
Spain
59
46
293
106
United Kingdom
115
66
173
57
Slovenia
6.1%
5.4%
8.0%
9.9%
3.8%
3.6%
3.8%
3.5%
prevalence (%)
0.0
Europe (2)

[ 31 ]
149
102
566
200
Lithuania
344
214
688
236
Russia
107
65
259
77
Poland
48
30
219
65
Sweden
458
312
504
220
Ukraine
223
170
658
352
Turkmenistan*
41 34
9 3
Turkey
272
209
351
128
Yugoslavia*
196
158
209
86
Macedonia
282
225
592
368
280
194
351
155
Romania
145
122
267
161
Tajikistan*197
153
454
291
Uzbekistan*
– 5.5% 0.3%
4.5%
–
6.4%
5.7%
3.2%
–
3.5%
–
–
–

[ 32 ]
prevalence (%)
0.0
42 32
224
90
United States of America
56 48
127
67
Mexico
119
98
133
108
Belize
177
160
89
54
Jamaica
312
182180
46
Guyana
143
77
208
83
Bahamas
184
123
374
227
Trinidad and Tobago
108
129
101
25
Dominica, Commonwealth of
175
64
99
53
Antigua and Barbuda*
121
56
112
62
Barbados
3.4%
8.0%
3.1%
92
48
– –
Martinique*
–
184 185
130
61
St Lucia*
–
–
5.0%
8.0%
8.5%
14.2%
15.0%
14.1%
13.2%
34 24
183
62
Canada
North America
prevalence

[ 33 ]
Paraguay
Argentina
Chile
Cuba
Guatemala
Nicaragua
Panama
Peru
Suriname
Uruguay
Venezuela
Colombia
Dominican Republic
Puerto Rico
24 30
43
25
73
47
96
56
61
49
62
40
85 77
222
134
45 41
57
33
43
22
170
69
82 76
173
100
94
75
223
110
88 80
219
103
119
96
123
61
107
74
181
65
122
68
140
39
96
59
121
49
23 2028
14
8.6%
–
2.9%
El Salvador
58
46
65
40
4.8%
Costa Rica
53
40
145
84
3.4%
2.9%
Ecuador
55
4135
18
3.0%
3.7%
1.4%
3.3%
4.5%
4.5%
4.2%
4.1%
4.0%
8.9%
5.3%
Brazil
121
74
117
73
3.2%
prevalence (%)
0.0
South and Central America
prevalence

[ 34 ]
248
139
371
181
Mauritius
44
24
92
25
Sri Lanka
2.9%
prevalence (%)
0.0
15.0%
South East Asia
prevalence

[ 35 ]
prevalence
225
150
76
51
China, Peoples' Republic of
102
87
242
114
Singapore, Republic of
111
63
125
58
Philippines
34 29
164
73
Australia
153
114
181
98
Mongolia*
2.7%
–
191
121
38
14
Korea, Republic of
6.1%
73
4145
16
Japan
7.4%
65
47
80
34
Hong Kong SAR, PRC
3.1%
6.0%
60
48
309
117
New Zealand
8.0%
56
44
171
70
Guam*
–
128
78
25
51
Taiwan
9.1%
11.3%
prevalence (%)
0.0
–
American Samoa*
317
256
152
41
–
37
214
3748
Palau*
9.1%
Fiji*
177
479
66
100
–
Northern Mariana Islands*
77
56
174
0
–
Cook Islands*
129
149
0
228
12.1%
Western Pacific

[ 37 ]
Double Jeopardy
Diabetes and Cardiovascular
Disease: Double Jeopardy
C H A P T E R 3
In the previous two chapters we saw the
extent of both diabetes and cardiovascular
disease amongst the general population.This
chapter brings the two diseases together and
addresses specifically
the topic of
cardiovascular disease
in the setting of
diabetes.
People with diabetes
are two to four times
more likely to develop
cardiovascular disease
than people without
diabetes, making it the most common
complication of diabetes.The data presented in
Chapter 2 show that cardiovascular death rates
are either high or appear to be climbing in
countries where diabetes is prevalent. When
we consider that the number of people with
diabetes around the world is predicted to
double over the coming decades, the outlook
for cardiovascular disease becomes even more
alarming.
The recent decline in cardiovascular disease in
the USA, Australasia and western Europe may
be compromised significantly by this upsurge in
diabetes. In other parts of the world, where
cardiovascular disease has been proliferating in
recent years, the additional impact of diabetes
threatens to have devastating consequences.
In short, the predicted escalation in diabetes
prevalence is likely to contribute to a
cardiovascular disease epidemic, particularly in
the developing world - unless preventive
measures are taken as a matter of urgency.
A Costly Situation
Diabetes is already consuming up to 10 percent
of total national healthcare budgets in many
countries. About half of this expense can be
attributed to the costs of managing diabetes
complications. As reflected in the patterns of
hospital admissions for the treatment of
complications, cardiovascular complications
account for the bulk of this (Figure 15). It is
therefore clear that the current situation has
enormous implications in both human and
economic terms.
The public health impact of cardiovascular
disease in diabetes is exacerbated by the
following factors:
• Type 2 diabetes is occurring at an earlier
age, thereby precipitating the threat of the
premature onset of cardiovascular
complications.
• The discovery of insulin has extended the
life expectancy of people with type 1
diabetes significantly. Each year of prolonged
life brings about a greater risk of
cardiovascular complications.
How does Diabetes Lead to
Cardiovascular Disease?
All types of diabetes can lead to diseases
within the heart and circulatory system in a
number of ways. In many people with diabetes
these different factors co-exist, resulting in
progressive damage to the heart and blood
vessels.
As we saw in the previous chapter (page 19),
the two main processes which lead to
cardiovascular disease are atherosclerosis and
hypertension.
People with
diabetes are two to
four times more
likely to develop
cardiovascular
disease than people
without diabetes.
Fact

[ 38 ]
1. Atherosclerosis
Not only are people with diabetes at increased
risk of developing atherosclerosis, but the
process also tends to be accelerated, more
severe and more widespread.This can cause
serious clinical consequences in younger
individuals. Since atherosclerosis damages the
medium and large blood vessels, the term
macroangiopathy is often used to indicate its
presence in people with diabetes.
Atherosclerosis in diabetes results from a
complex interplay between a number of risk
factors.These are described in more detail in
Chapter 4.
2. Hypertension
Hypertension is at least twice as common in
people with diabetes as in the general
population, and is also more frequent in people
with impaired glucose tolerance.
As well as atherosclerosis and hypertension, there
are other damaging effects which are specific to
diabetes: microangiopathy, autonomic
neuropathy and other abnormalities of the
blood vessels.These processes worsen vascular
function and therefore make the consequences of
atherosclerosis/macroangiopathy and hypertension
more difficult to withstand. In addition, they lead
to other diabetic complications such as
nephropathy and impotence.
3. Microangiopathy
Microangiopathy refers to damage to the small
blood vessels and capillaries, and is largely
restricted to people with diabetes. It is a direct
result of chronic hyperglycaemia. Other factors
such as hypertension and dyslipidaemia also
contribute.
The causal link between hyperglycaemia and
microangiopathy has been emphasized by a
number of recent clinical trials, all of which show
that the microangiopathic complications of
diabetes are the most readily preventable with
good glycaemic control.The largest of these
studies are the Diabetes Control and Complications
Trial (DCCT) in type 1 diabetes and the United
Kingdom Prospective Diabetes Study (UKPDS) in type
2 diabetes.
Microangiopathy adversely affects capillary
function leading to a shortage of supply of oxygen
and nutrients to the tissues, and a leakage of
proteins into the tissue spaces. Capillaries
Neuropathy
Kidney disease
Total cardiovascular disease
Acute complications
Other
United Kingdom
Eye disorders
Figure 15: Proportion of hospital bed days used for the treatment of diabetic complications
Argentina
All microvascular Other acute
Cardiovascular disease
Infections
Other

[ 39 ]
throughout the body are affected, but damage to
the microcirculation of the eyes, kidneys and
nerves is responsible for the major clinical
manifestations – retinopathy, nephropathy,
neuropathy and the diabetic foot.
4. Autonomic Neuropathy
Diabetes can affect different components of the
nervous system. One component, known as the
autonomic nervous system, provides a nerve
supply to the internal organs of the body, including
the heart and blood vessels. Damage to this
system is known as autonomic neuropathy.
Damage to the autonomic nervous system can be
a direct result of chronic hyperglycaemia or, in
turn, can follow microangiopathy involving the
small vessels which supply blood to the nerves
themselves, thereby causing a vicious cycle of
nerve and blood vessel damage. Damage to the
nerve supply of the heart affects the regulation of
the pulse rate. In the blood vessels, manifestations
such as a fall in blood pressure on standing or
exercising can produce disabling symptoms and
can affect measures aimed at treating
hypertension. Loss of the nerve supply to small
blood vessels can also impair the regulation of
blood flow. This is an important contributory
factor to the development of diabetic foot
ulcers.Autonomic neuropathy is an important
cause of impotence in men with diabetes. It can
also affect the function of the bladder, stomach
and intestine.
Autonomic neuropathy Microangiopathy
Nephropathy
Heart rate
disturbances
Postural
fall in
blood
pressure
Diabetic foot
Retinopathy
Neuropathy
Gastro-
intestinal
dysfunction
Impotence
Dysfunction
of bladder
Figure 16: Clinical outcomes of microangiopathy
and autonomic neuropathy
Microangiopathy Autonomic neuropathy Other blood vessel damage
• Damage to small • Damage to the nerve • Damage to the inner
blood vessels and supply of the internal or outer lining of blood
capillary circulation. organs of the body. vessels.
• Retinopathy • Problems with the • Impaired regulation
• Nephropathy pulse rate of blood flow
• Neuropathy • Postural fall • Weakened vessel walls
• Diabetic foot in blood pressure • Aggravated
• Foot ulcers microangiopathy
• Impotence and atherosclerosis/
• Gastro-intestinal macroangiopathy
dysfunction
Table 10:Abnormalities of the cardiovascular system specific to diabetes
WHAT
ISIT?
CLINICAL
OUTCOME

[ 40 ]
5. Other Abnormalities of Blood Vessels
Diabetes can also damage blood vessel walls in
other ways, which can interact with both
atherosclerosis/macroangiopathy and
microangiopathy to aggravate the situation.
The inner lining of blood vessels known as the
endothelium can be damaged, for example
affecting the ability of the blood vessels to
relax or dilate.This may impair the regulation
of the blood flow. Endothelial dysfunction is an
important component of both macroangiopathy
and microangiopathy, but can also appear early
in the course of diabetes before the onset of
detectable vascular disease.
The outer layers of the vessel wall, composed
of muscle or elastic tissue, can also be
damaged.This can impair the regulation of the
blood flow and may weaken the vessel wall.
Outer lining
Middle muscle layer
Inner lining
(endothelium)
Figure 17: Blood vessel
To complicate matters further, common
chronic diabetes complications such as
neuropathy and nephropathy can themselves
have adverse effects on the heart and
circulation.As a result, as diabetes progresses
the heart and blood vessels are exposed to
multiple attacks, all of which can interact with
each other to produce severe consequences.
The Cardiovascular Disease
Triad in Diabetes
In practice the most important clinical
manifestations of diabetic vascular disease can
be divided into the same three groups
described in Chapter 2: those affecting the
coronary circulation, those affecting the
cerebral circulation and those affecting the
lower limbs.The clinical manifestations
described in Chapter 2 still apply but are
particularly severe and may be modified by the
presence of additional factors or complications
related to diabetes.
Angina (see page 20):When autonomic
neuropathy is present,
the typical pain of angina
which is usually
associated with
ischaemia may not be
experienced, leading to
silent ischaemia.This
may manifest itself just
with shortness of breath
Coronary heart disease Cerebrovascular disease Peripheral vascular disease
• Angina (including • Stroke • Gangrene
• silent ischaemia) • Transient ischaemic • Intermittent
• Heart attack (including • attack • claudication
• silent heart attack) • Dementia • Foot ulcers
• Sudden death
• Heart failure
• Fainting attacks
Table 11:The clinical manifestations of cardiovascular disease in diabetes
CLINICAL
MANIFESTATIONS
People with type 2
diabetes have the
same risk of heart
attack as people
without diabetes
who have already
had a heart attack. Fact

[ 41 ]
or other more vague symptoms such as nausea
or sweating.
Heart attack (see page 20): People with type 2
diabetes with no prior history of heart attacks
have as great a risk of having a heart attack in
the future as people without diabetes who have
already experienced a heart attack (Figure 18).
Also, since people with
diabetes often have
widespread vascular
disease, the
consequences of a
heart attack are often
more severe than in
people without
diabetes, resulting in greater difficulty with
emergency treatments.
When autonomic neuropathy is present, heart
attacks can be ‘silent’, with an absence of chest
pain and presentation with less specific
symptoms.This means that the diagnosis can
easily be overlooked and, in effect, people with
diabetes can have a
heart attack without
even realizing it.
For these and other
reasons, people with
type 2 diabetes have a
higher risk of death
following a heart attack
(Figure 19).
Sudden death (see page
20): In diabetes, sudden
death can also result
from abnormalities in the heart’s rhythm
provoked by autonomic neuropathy. Men with
diabetes are subject to
sudden death 50% more
often and women with
diabetes 300% more
often than their
counterparts without
diabetes of the same
age.
0
10
20
30
40
50
Incidence(%)
People without diabetes People with diabetes
No prior heart attack Prior heart attack
Figure 18: Heart attacks in people with and
without diabetes over a period of seven years
Adapted from: Haffner SM, et al (1998)
0
10
20
30
40
50
Mortality(%)
People with diabetesPeople without diabetes
Men Women
Figure 19: Deaths in people with and without
diabetes in the year following a first heart attack
Adapted from: Miettinen H, et al (1998)
can have a heart
attack without even
realizing it.
Fact
have a two to three-
fold greater risk of
heart failure
compared to people
without diabetes.
Fact
Men with diabetes
are subject to
sudden death 50%
more often and
women with
diabetes 300%
more often than
their counterparts
without diabetes of
the same age.
Fact

[ 42 ]
Heart failure (see page 20): Heart failure is a
common complication of diabetes and again
carries a high short-term mortality rate. In
diabetes, heart failure may also occur as a
consequence of microangiopathy. People with
diabetes have a two to three-fold greater risk
of heart failure compared to people without
diabetes.
Fainting attacks:Autonomic neuropathy can lead
to fainting attacks by causing either
disturbances of the heart rhythm or a fall in
blood pressure on standing or exertion.
Stroke (see page 21):
Strokes occur twice as
often in people with
diabetes and
hypertension as in
those with
hypertension alone.
The clinical features
are generally similar to
those seen in people without diabetes.
However the additional involvement of
microangiopathy in diabetes can lead to a
worse outcome.
Transient ischaemic
attack (see page 21):
Transient ischaemic
attacks (mini-strokes)
occur between two
and six times more
frequently in people
with diabetes.
Dementia (see page 21):The additive effects of
multiple small strokes, together with
microangiopathy affecting the small blood
vessels to the brain, lead to an increased
likelihood of dementia in people with diabetes.
People with diabetes account for the majority
of cases of lower-limb amputation resulting
from vascular disease. In fact they are 15-40
times more likely to require such an
amputation compared to
the general population.
The factors which
predispose to this
greater risk are
described below.
Gangrene (see page 22):
Although lower-limb
gangrene also occurs in
people without diabetes, the vascular disease
which is particular to diabetes makes it much
more common. Diabetic gangrene can also
result from disease of the smaller blood vessels
producing localized damage, for example in the
toes. People with diabetes over the age of 70
have a 70-fold increased risk of lower-limb
gangrene compared to
people without diabetes
of the same age.
Intermittent claudication
(see page 22):
Intermittent claudication
(calf pain) occurs three
times more often in men
with diabetes and almost
nine times more often in
women with diabetes
than in their
counterparts without diabetes.The presence of
extensive, severe vascular disease in diabetes
may influence the type of treatment chosen
and may hamper its success (in particular
surgical treatment).
Foot ulcers: Foot ulcers can occur as a result of
either localized gangrene (usually affecting the
toes) or diabetic neuropathy (usually arising at
pressure points or weight-bearing areas of the
feet).The underlying predisposing factors are
many and complicated but the vascular
complications of diabetes, particularly
microangiopathy and autonomic neuropathy,
are very important.
Strokes occur twice
as often in people
with diabetes and
hypertension as in
those with
hypertension alone.
Fact
Transient ischaemic
attacks occur
between two and six
times more
frequently in people
with diabetes.
Fact
are 15-40 times
more likely to
require a lower-limb
amputation
compared to the
general population.
Fact
People with
diabetes over the
age of 70 have a
70-fold increased
risk of lower-limb
gangrene compared
to people without
diabetes of the
same age.
Fact

[ 43 ]
Figure 20: Causes of death in people with diabetes in the US
Adapted from: Geiss LS, et al (1995)
0
10
20
30
40
50
60
70
80
OtherStrictly diabetes-relatedCardiovascular disease
Mortality(%)
The Vicious Cycle
As we have seen, diabetes can lead to
cardiovascular damage in a number of ways.
These processes do not develop independently,
as each may accelerate or worsen the others.
This means that when people with diabetes
develop for example a heart attack or stroke,
the prognosis is worse than for people without
diabetes because of the vicious cycle caused by
the combined vascular abnormalities associated
with diabetes.
Indeed, cardiovascular disease is the leading
cause of death in people with diabetes in
developed countries (Figure 20).

[ 45 ]
Risk Factors
Risk FactorsC H A P T E R 4
What is a Risk Factor?
A risk factor is a condition that places an
individual at risk of developing a health-related
problem.The term has become widely used to
address the causes of chronic, multifactorial
diseases such as diabetes and cardiovascular
disease. A risk factor can be genetic or
acquired. It may be identified as a single
measurement (eg a physical feature such as
weight), a disease (eg hypertension) or a
lifestyle characteristic (eg smoking). In order to
be considered a risk factor for a disease, the
condition must be associated with that disease
in a manner which is beyond chance alone. A
causal link is therefore implied. However, a risk
factor will not necessarily always lead to the
development of the disease.
A risk factor must be distinguished from a risk
marker and a disease marker. A risk marker is a
condition which is associated with a higher risk
of developing a disease, but the association has
not yet proven to be causal.A disease marker
is a condition which indicates that a disease is
already present.
The ultimate purpose of identifying a risk
factor is to modify it in order to prevent the
disease. If the modification of the risk factor
results in a significant reduction of the disease
outcome, that risk factor is a main target for
intervention. If the risk factor cannot be
modified but its association with the disease is
strong (eg gender or age), it may be used to
select high-risk subjects who could benefit
from special preventive interventions.
Cardiovascular Risk Factors
• Advancing age
• Diabetes and other high blood
glucose conditions
• Dyslipidaemia
• Genetic background
• High alcohol consumption
• Hypertension
• Left ventricular hypertrophy
• Male gender
• Menopause
• Obesity
• Sedentary lifestyle
• Smoking
Table 12: Risk factors for cardiovascular disease in
the general population
The risk factors for cardiovascular disease in
the general population are listed in alphabetical
order below:
Advancing age: The risk of cardiovascular disease
grows with age. It is significantly higher in men
over 45 years of age and in women over 55
years of age.
Diabetes and other high blood glucose conditions: As
described in Chapter 3, diabetes is closely
associated with a greater risk of the premature
onset of cardiovascular disease.
Dyslipidaemia: Elevated blood levels of total
cholesterol and of low-density lipoprotein
(LDL) cholesterol, as well as low levels of
high-density lipoprotein (HDL) cholesterol
are risk factors for cardiovascular disease.
There is a continuous relationship between the
levels and the risk. In some cases raised
RISKFACTORS

[ 46 ]
triglyceride levels in the blood are also an
independent risk factor.
Genetic background: Although the responsible
genes have not been identified, a high risk of
cardiovascular disease may be hereditary and can
be identified in people with parents or siblings
who have a history of cardiovascular disease at a
premature age (ie before 55 years of age in men
and 65 years of age in women).
High alcohol consumption: Excess alcohol intake
can worsen other risk factors such as
hypertension.
Hypertension: Arterial pressure above the normal
range (135mm Hg systolic and 85mm Hg
diastolic) constitutes a risk factor for
cardiovascular disease. As with lipids, there is a
continuous relationship between the levels and
risk. Risk may commence at lower levels of blood
pressure in some susceptible individuals.
Insulin resistance: Recently it has been shown that
people with resistance to the action of insulin at
the cellular level have a greater risk of
Left ventricular hypertrophy: The increased
thickness of the heart’s left ventricular muscle is
also a risk factor for cardiovascular disease.
Initially it is a silent condition which has to be
investigated by cardiac tests. It is mainly present
in people with hypertension.
Male gender: Men have a higher risk of
cardiovascular disease than women of the same
age.
Menopause: Pre-menopausal women are
protected from developing cardiovascular disease
because the oestrogen made in their ovaries
protects their hearts.The risk of cardiovascular
disease increases in women after the menopause
because the protective effect of oestrogen is lost.
Obesity: Excess body fat has a marked adverse
influence on risk factors such as hypertension,
dyslipidaemia, diabetes and other forms of
impaired glucose regulation. It can be identified
by a high body mass index (BMI).The adverse
effect of excess weight is more pronounced
when the fat is concentrated mainly in the
abdomen (central obesity), as often happens in
men.This can be identified by a high waist/hip
ratio.
Sedentary lifestyle: Diminished physical activity has
been shown in the population at large to be
associated with an intensified risk of
Smoking: Cigarette smoking in particular is a risk
factor for cardiovascular disease.The risk starts
with any daily amount and can be rapidly
abolished by stopping the habit.
It is important to emphasize that the presence of
multiple cardiovascular risk factors has a
multiplicative and not an additive effect upon the
incidence of coronary heart disease in the
general population (Figure 21).
Diabetes and Other High
Blood Glucose Conditions:
A Major Risk Factor
Because of the soaring prevalence of diabetes
worldwide, it now rivals smoking, hypertension
and cholesterol disorders as a major risk factor
for cardiovascular disease. Diabetes also
belongs to a special risk category as it so
markedly increases the risk of cardiovascular
disease (Figure 22).
Other Cardiovascular Risk Factors
in People with Diabetes
A Higher Prevalence
All cardiovascular risk factors apply to people
with diabetes. Indeed they are even stronger
determinants in this group (Figures 23 to 26
and Table 13).This may be partly explained by
the fact that people with diabetes have a higher
prevalence of many cardiovascular risk factors,
notably lipid disorders, hypertension, obesity
and insulin resistance.These risk factors are
interrelated and are more prominent in type 2
diabetes than type 1.

[ 47 ]
0
10
20
30
40
50
60
Estimatedrateofcoronaryheartdisease(%)
Risk factors
Men Women
Systolic blood pressure (mm Hg)
Cholesterol (mg/dL)
HDL cholesterol (mg/dL)
Diabetes
Cigarette smoking
Left ventricular hypertrophy
120
220
50
–
–
–
160
220
50
–
–
–
160
259
50
–
–
–
160
259
35
–
–
–
160
259
35
+
–
–
160
259
35
+
+
–
160
259
35
+
+
+
Figure 21: Estimated coronary heart disease rate according to various combinations of risk factors over 10 years
Adapted from: Kannel WB (1996)
0
2
4
6
8
10
StrokeIntermittent
claudication
Heart failureCoronary
heart disease
Total cardiovascular
disease
Relativerisk
Men Women
1
Figure 22: Relative risk* of cardiovascular events in people with diabetes
Adapted from:Wilson PWF, et al (1992)
* The relative risk is the relation between the cardiovascular risk of people with diabetes and the
cardiovascular risk of the general population (which equals one).Therefore a relative risk ratio of two for
people with diabetes here indicates a doubling of cardiovascular risk compared to the general population;
a relative risk ratio of four indicates a quadrupling of risk, etc.

[ 48 ]
Figure 26: Prevalence of cigarette smoking in people with diabetes
ArizonaHavanaTokyoHong KongNew DehliBerlinMoscowLondon
0
10
20
30
40
50
60
70
80
Prevalence(%)
Men
Women
Figures 23 to 26: Cardiovascular risk factors in people with diabetes in different populations
Adapted from: Keen H, et al (1985)
Figure 23: Prevalence of high cholesterol levels (≥ 4.65 mmol/l) in people with diabetes
0
20
40
60
80
100
Prevalence(%)
Men
Women
Figure 24: Prevalence of hypertension (blood pressure ≥ 160/95 mm Hg) in people with diabetes
(These prevalence rates would be even higher if the current cut-off values were applied)
0
10
20
30
40
50
Prevalence(%)
Men
Women
Figure 25: Mean body mass index (kg/m2
) in people with diabetes (see glossary for BMI values)
0
5
10
15
20
25
30
35
Bodymassindex
Men
Women

[ 49 ]
people with diabetes, along with the treatment
of diabetes itself.
But even when other risk factors are taken into
account, people with diabetes are still more
likely to die as a result
of cardiovascular
disease.This implies that
some other factor is
responsible.This factor
could be related to
diabetes itself. Since the
main characteristic of
diabetes is high blood
glucose, it is tempting to
assume that
hyperglycaemia is the
main cardiovascular risk
factor in this group.The
United Kingdom
Prospective Diabetes Study (UKPDS) has
shown that there is a significant linear
correlation between haemoglobin A1c
(which reflects mean blood glucose levels over
the past three months) and macrovascular
events in type 2 diabetes.
It appears however that any increase in glucose
levels above normal is associated with a higher
risk of coronary heart disease (Figure 27).This
A Stronger Impact
It has also been demonstrated that most
cardiovascular risk factors have a more harmful
impact in the presence of diabetes. For
example, having diabetes lowers by ten years
the risk attributed to age in both men and
post-menopausal women.As regards the risk
attributed to gender, women with diabetes lose
the pre-menopausal protective effect of
oestrogen and therefore have the same age-
related risk as men.This implies that there
should be a higher relative priority given to the
public health and clinical management of
cardiovascular risk in women with diabetes
than in the general population, where females
are relatively protected from at least the
coronary heart component of cardiovascular
disease. Also, although prevalence rates are
similar, the cardiovascular risk attributed to
high blood cholesterol is doubled in the
presence of diabetes.
The Role of Hyperglycaemia
About 50% of the excess risk of cardiovascular
disease in type 2 diabetes can be explained by
the higher incidence and/or the stronger
impact of conventional risk factors.The
implication of this is that the lowering of these
other risk factors should also be a priority in
Risk factor Prevalence
Hypertension • Prevalence is at least double in people with type 2 diabetes.
High blood cholesterol • Prevalence is similar in people with diabetes.
High triglycerides with low HDL • Prevalence is higher in people with diabetes.
Left ventricular hypertrophy • Most commonly seen in people with long-standing high
blood pressure, but is also seen in the absence of elevated
blood pressure in people with diabetes.
Obesity • Prevalence is stronger in people with diabetes.
Weight distribution is also usually different, with more
central obesity which is linked with a tendency to develop
coronary heart disease.
Smoking • People with diabetes smoke less (presumably due to
medical advice).
Table 13:Prevalence of cardiovascular risk factors in people with diabetes compared to people without diabetes
About 50% of the
excess risk of
cardiovascular
disease in type 2
diabetes can be
explained by the
higher incidence
and/or higher
impact of
conventional risk
factors.
Fact

[ 50 ]
includes impaired fasting glycaemia (IFG) and
impaired glucose tolerance (IGT). It is
important to note that the risk associated with
IGT is approximately double that seen in
people with normal glucose levels, and already
approaches the level of risk of people with
newly-diagnosed diabetes.As the relationship
between glucose levels and risk is continuous,
the risk becomes even higher with established
diabetes, particularly if it is poorly controlled
or of long duration. Although proof of a direct
causal relationship is still missing and the exact
mechanisms are not fully understood, there is
no doubt that raised glucose levels constitute a
risk factor for cardiovascular disease in both
people with and without diabetes.
Multiple Risk Factors
Many people with diabetes have several risk
factors. As we saw in Figure 21, the presence
of several risk factors
has a multiplicative and
not just an additive
effect.The situation is
even more serious in
people with diabetes
as, for each risk factor
present, cardiovascular
mortality is about
three times greater than in the general
population (Figure 28).
Type 1 Diabetes
People with type 1 diabetes also have an
increased risk of coronary heart disease,
although few studies
have been carried out to
attest this. It seems
prudent on the basis of
clinical judgment to
consider that people
with type 1 diabetes
over the age of 30 years
are similar to people
with type 2 diabetes as
regards coronary heart
disease risk. People with
type 1 diabetes who suffer from diabetic
nephropathy, regardless of age, should be
treated as being at particularly high risk.
New Cardiovascular Risk Factors
and Diabetes
Microalmubinuria, which is a well-known
disease marker for early diabetic nephropathy,
has also been shown to be a risk factor for
cardiovascular disease in people with diabetes.
The explanation seems to be related to the
0
1
2
3
4
5
Known diabetesNewly-diagnosed diabetesImpaired glucose tolerance
(IGT)
Normal glucose levels
Coronaryheartdiseasemortality
(incidencerateper1000personsperyear)
Figure 27: Mean coronary heart disease mortality rates by degree of glucose tolerance
Adapted from: Eschwège E, et al (1985)
For each risk factor
present, the risk of
cardiovascular death
is about three times
greater in people
with diabetes as
compared to people
without the
condition.
Fact
People with type 1
diabetes over the
age of 30 years
have a coronary
heart disease risk
similar to people
with type 2
diabetes. Fact

[ 51 ]
fact that microalbuminuria indicates the
presence of vascular damage.
A number of other new cardiovascular risk
factors have also been identified, although most
of them are still considered as risk markers.
The more noteworthy of these are
homocysteine, lipoprotein (a) and C-
reactive protein.At the present time there is
insufficient evidence available to justify
including them as part of a routine risk
assessment.
Conclusion
Due to the higher prevalence and impact of
cardiovascular risk factors, as well as the role
of hyperglycaemia, people with diabetes
without overt cardiovascular complications
merit an intervention against risk factors which
is as aggressive as that which would normally
be provided for individuals with established
Figure 28: Impact of multiple risk factors in the
presence of diabetes
Adapted from: Stamler J, et al (1993)
0
30
60
90
120
150
People without diabetes People with diabetes
Cardiovasculardiseasemortality
(per10,000personsperyear)
Number of risk factors
(smoking, high cholesterol levels, hypertension)
0 1 2 3

[ 53 ]
Reducing the Risks
Reducing the RisksC H A P T E R 5
Management of Risk Factors
in the General Population
Many cardiovascular deaths are potentially
preventable if we can modify known risk
factors.While some risk factors are fixed (such
as age, gender and genetic background), many
others are modifiable (Table 14). Given that
risk factors often occur together, all should be
treated to gain the most benefit in terms of
reducing cardiovascular disease.
• Diabetes and other high blood
glucose conditions
• Dyslipidaemia
• High alcohol consumption
• Hypertension
• Obesity
• Sedentary lifestyle
• Smoking
Table 14: Modifiable cardiovascular risk factors in
the general population
Modifiable cardiovascular risk factors in the
general population are listed in alphabetical
order below:
Diabetes and other high blood glucose conditions:
Although, as stated in Chapter 4, high glucose
levels constitute a cardiovascular risk factor in
people with and without diabetes, there is at
present no evidence that the treatment of
minor increases in blood glucose (which fall
short of overt diabetes) decreases the
subsequent development of cardiovascular
disease. At the very least however, the finding
of any rise in glucose levels should promote a
careful search for and treatment of other
cardiovascular risk factors.
Dyslipidaemia (see page 45):There is strong
evidence that reducing elevated levels of LDL
cholesterol diminishes the risk of coronary
heart disease. High levels of HDL cholesterol
are also known to decrease the risk of
coronary heart disease.Therefore raising HDL
cholesterol in people with low HDL
cholesterol levels may provide benefit. It is also
likely that lowering high triglycerides has a
similar effect. Reducing lipid levels may also be
beneficial in the prevention of stroke and
peripheral vascular disease.
The first line of treatment is lifestyle
modification by improving diet, taking more
physical exercise and losing excess body weight.
If these measures fail then drug treatment can
also be prescribed. A group of drugs called
statins are particularly useful for lowering LDL
cholesterol. Another group known as fibrates
can be used to target triglycerides.
Combinations of these can be used if required.
Hypertension (see page 46):The lowering of
elevated blood pressure substantially cuts the
risk of stroke and coronary heart disease. If
lifestyle measures including salt restriction are
insufficient then antihypertensive drugs (eg
angiotensin converting enzyme (ACE)
inhibitors, beta blockers, calcium channel
blockers, diuretics) should also be
administered. It is worth noting that many
people will require more than one drug.
Insulin resistance (see page 46): Insulin
resistance is usually either caused or
aggravated by obesity, particularly abdominal
obesity. Hence diet to promote the loss of
excess weight, together with exercise to
improve muscle metabolism and aid weight loss
can improve insulin sensitivity. When diabetes is
present, tight glucose control can also enhance
MODIFIABLE
RISKFACTORS

[ 54 ]
insulin sensitivity. Drugs which specifically
target insulin resistance are now becoming
available, but it is not yet known whether
decreasing insulin resistance will in itself slow
or prevent the development of cardiovascular
disease.
Obesity (see page 46): Sustained weight loss in
the overweight is of benefit for all
cardiovascular diseases. It is also instrumental
in decreasing other risk factors such as raised
blood pressure and high lipids.
Risk factor Treatment Results of treatment
Diabetes and other • Lifestyle modifications Although it prevents coronary
high blood glucose • Drugs: oral hypoglycaemic heart disease, at present the effect
conditions agents, insulin. of blood glucose lowering alone
may not be as strong as the
modification of other major
risk factors.
Dyslipidaemia • Lifestyle modifications: eg diet, Decreases the risk of coronary
physical exercise and lowering heart disease. May also be beneficial
excess body weight. in the prevention of peripheral
• Drugs: statins, fibrates or a vascular disease and stroke.
combination of the two.
High alcohol • Lifestyle modifications: Lowers the risk of stroke and
consumption drink in moderation. coronary heart disease.
Hypertension • Lifestyle modifications: Reduces the risk of stroke and
eg salt restriction. coronary heart disease.
• Drugs: beta blockers, calcium
channel blockers,ACE inhibitors,
diuretics, etc.
Insulin resistance • Lifestyle modifications: It is not yet known whether
diet, exercise. decreasing insulin resistance will
• Tight glucose control in in itself slow or prevent the
diabetes. development of cardiovascular
disease.
Obesity • Lifestyle modifications: Prevents all cardiovascular
achieving normal body weight, diseases. Decreases other risk
increasing physical activity. factors such as blood pressure,
high glucose and high lipids.
Sedentary lifestyle • Lifestyle modifications: Reduces body fat, raises HDL
increasing in particular cholesterol levels, lowers LDL
aerobic physical activity. cholesterol and triglyceride levels,
increases insulin sensitivity, and
lowers blood glucose and blood
pressure.
Smoking • Lifestyle modifications: Prevents coronary heart disease,
stopping smoking. stroke and peripheral vascular
disease.
Table 15: Management of cardiovascular risk factors in the general population

[ 55 ]
Sedentary lifestyle (see page 46):There is
compelling evidence that aerobic physical
activity reduces the risk of coronary heart
disease. People who exercise regularly have less
body fat, higher HDL cholesterol levels, lower
LDL cholesterol and triglyceride levels, greater
insulin sensitivity, lower blood glucose and
blood pressure, and usually have an improved
sense of well-being.
Smoking (see page 46): Stopping smoking is of
major benefit in the prevention of coronary
heart disease, stroke and peripheral vascular
disease, even in those who have smoked for a
very long time.
Some risk factors cannot be easily measured
and others may remain to be identified. For this
reason, certain interventions may be found to
be very effective even though they do not
target a specific measured risk factor. A good
example of this is aspirin, which has proved of
major benefit in preventing coronary heart
disease.
in People with Cardiovascular
Disease
Even greater attention should be paid to risk
factors in people who have already developed
cardiovascular disease. For instance smoking
must be avoided, and all people with coronary
heart disease should be taking aspirin (unless a
specific contraindication to its use is present).
Meticulous attention to blood pressure and
lipid control is also vital.
As many people with diabetes who experience
a first coronary event die prior to getting to
hospital, they cannot benefit from secondary
prevention strategies. In view of this, as well as
the increased overall risk associated with
diabetes, the management of risk factors in
people with diabetes should precede the onset
of heart or other vascular disease and should
be pursued as aggressively as it would be in
individuals with established vascular disease.
As is the case for the general population, the
first line of action in managing risk factors in
people with diabetes should be lifestyle
modifications. If this is not sufficient then drugs
can also be prescribed.The lifestyle and drug
measures summarized in Table 15 also apply to
people with diabetes. In addition, screening for
microalbuminuria (see page 50) is important,
and specific interventions can help delay its
progression.
Although people with diabetes and their
physicians may be reluctant to add another
drug to an already overwhelming regimen of
medication, a number of recent studies have
shown the extent to which some risk factors
can be modified by medication in people with
the condition.The results of these studies are
summarized below and in Table 16.
Dyslipidaemia
A subgroup analysis of the Scandinavian
Simvastatin Survival Study (4S) showed the
benefits of decreasing LDL cholesterol levels
with a statin in people with diabetes and
coronary heart disease.This produced an even
greater reduction in the rate of coronary
events than in people without diabetes (55%
versus 32%). In the diabetes group there was a
saving of one life for every four patients
treated, as opposed to one in 13 in the group
of people without the condition.
In the Cholesterol and Recurrent Events Trial
(CARE) the people studied also had coronary
heart disease, but had lower cholesterol levels.
Statin therapy in this study cut the risk of
coronary events by a similar degree in people
with and without diabetes.
The aim of the Veterans Affairs HDL Intervention
Trial (VA-HIT) was to use fibrate therapy to
raise HDL cholesterol and lower triglycerides
in men with documented coronary heart
disease and low HDL cholesterol. In the
diabetic group there was a 22% relative risk
reduction of a first non-fatal heart attack or

[ 56 ]
coronary heart disease death, and a significant
decline in cerebrovascular events.
It is thus clear that lipid lowering with either
statins or fibrates is beneficial in people with
type 2 diabetes, particularly if they already have
coronary heart disease.Although there is
evidence to suggest the same benefit for
people with diabetes but without coronary
heart disease, this remains to be confirmed.
Hypertension
In the part of the UKPDS that dealt with
hypertension, people with type 2 diabetes were
randomized to intensive or conventional
treatment using either a beta blocker or an
ACE inhibitor.The average blood pressure was
improved by 10 mm Hg systolic and 5 mm Hg
diastolic.This resulted in a reduction of the
risks for heart failure (56%), stroke (44%) and
deaths related to diabetes (32%). Current
practice is to aim for normal blood pressure
values, particularly in those with other risk
factors and those who have already
experienced a cardiovascular event.
Strategy Complication Reduction of complication
Lipid control • Coronary heart disease mortality 36%1
• Major coronary heart disease event 55%1
• Any atherosclerotic event 37%1
• Cerebrovascular disease event 62%1
Blood pressure control • Cardiovascular disease 51%2
• Heart failure 56%3
• Stroke 44%3
• Diabetes-related deaths 32%3
Blood glucose control • Heart attack 37%3
1
The 4S Study
2
Hypertension Optimal Treatment (HOT) Randomised Trial
3
UKPDS
Table 16: Highest percentage reduction of the risk of diabetic complications in people with type 2 diabetes
shown in recent studies
Adapted from: International Diabetes Federation (1999)
Hyperglycaemia
Data from the UKPDS suggest that there is
benefit in tightly controlling blood glucose in
people with diabetes.This was particularly
evident in a group of overweight subjects who
were treated with an oral hypoglycaemic agent
(metformin), in whom
a 37% reduction in heart
attacks was recorded,
and also when blood
glucose lowering and
blood pressure control
were combined.The
latter finding emphasizes
the importance of
treatment strategies
aimed at multiple risk
factors.
It is worth noting that,
over time, a combination
of different oral agents
and insulin is required
for blood glucose
control in type 2 diabetes. In type 1 diabetes
there was also a hint in the DCCT that tight
control of blood glucose improves
cardiovascular outcomes.
While
cardiovascular
deaths have
declined in those
without diabetes in
developed countries,
in men with
diabetes the
decrease has been
modest, while in
women with
diabetes the rates
have actually
increased.
Fact

[ 57 ]
Putting the Theory into Practice
These positive results call for aggressive action
to be taken to treat the cardiovascular risk
factors that are common in people with
diabetes.
Despite these findings, a recent US study
revealed that while cardiovascular disease
mortality and particularly coronary heart
disease related deaths have declined in those
without diabetes, in men with diabetes the
decrease has been a modest 13%, while in
women with diabetes the rates have actually
increased by 23% (Figure 29).
This suggests that approaches proven to
reduce cardiovascular disease in people with
diabetes are frequently not implemented in
clinical practice.There is therefore a clear need
for improved awareness of treatment
possibilities among healthcare professionals.
Guidelines with specific targets for
cardiovascular risk factors in people with type 1
and type 2 diabetes have been published by the
European and Western Pacific Regions of IDF.
Many other national and regional guidelines also
exist. However it should be noted that the
relationship between risk factors and disease is
generally continuous and additional benefits may
be obtained by lowering risk factors even further.
Risk factors Targets
Dyslipidaemia • Decrease LDL cholesterol
levels
(<115mg/dl or 3 mmol/l*
)
• Raise HDL cholesterol levels
(>46 mg/dl or 1.2 mmol/l*
)
• Lower triglycerides
(<150 mg/dl or 1.7 mmol/l*
)
Hypertension • Lower blood pressure
(<135/85 mm Hg)
Hyperglycaemia • Reduce hyperglycaemia
(HbA1c <7%)
Table 17:Targets for common cardiovascular risk
factors in people with diabetes
*
These levels are based on IDF Europe’s guidelines.
Other guidelines, for example those from the USA
or Latin America, may give slightly different target
values.
Other Risk Factors
In people with diabetes other factors are also
associated with cardiovascular disease, such as
increased ‘stickiness’ of the blood and
hardening of arteries. It is not known at this
stage whether treatment of such factors is
beneficial.
National Approaches
to Prevention: Lifestyle
Preventing Diabetes and
Cardiovascular Disease
The global changes in lifestyle – such as a
higher intake of fat, salt and calories, as well as
decreased physical activity – have led to an
upsurge in cardiovascular disease and type 2
diabetes. In many countries specific
manifestations of lifestyle changes include an
increase in the amount of junk food consumed
and the replacement of physical activity by
-40
-30
-20
-10
0
10
20
30
People with diabetesPeople without diabetes
Coronaryheartdiseasemortality(%)
Men Women
Figure 29: Changes in coronary heart disease
mortality rates in the USA
Adapted from: Gu K, et al (1999)

[ 58 ]
television, video games and internet browsing.
Increasing urbanization and mechanization are
also responsible for the general decline in
physical activity levels.
It is obvious that lifestyle modification can be
of major benefit in preventing non-
communicable diseases such as cardiovascular
disease and diabetes. Although they may be
challenging for the individual to implement,
lifestyle changes are cheap, effective and free of
side effects.
On the national level, a broad population-based
approach to prevention is probably more cost-
effective than merely targeting high-risk
individuals, although both methods can be
effectively combined. Ideally a population-based
approach should begin in childhood when
health-risk behaviour begins. Parents, teachers
and peer groups should be involved in
imparting health education to children, as a
sharp rise in the prevalence of childhood
obesity and young-onset type 2 diabetes has
been recently reported from several countries.
Healthy eating habits should be encouraged,
emphasizing a reduction in total calories, fat
and sugar, and an increase in the intake of fibre,
fruit and vegetables.The ‘healthy option’ should
be made more accessible and affordable for all.
In the UK for example free fruit is now being
given to school children and wide publicity is
being given to the message that everybody
should eat five portions of fruit and vegetables
a day.
Regular physical exercise, eg aerobic exercises
like walking, jogging, swimming or cycling, can
help to prevent diabetes and reduce
cardiovascular disease risk factors. Relaxation
techniques can also play a role in the
prevention of cardiovascular disease. Exercise
can be promoted by initiatives such as
providing public sports facilities in the
community.
Cigarette smoking rates have already started
falling in the Western world but unfortunately
they are on the increase in developing
countries. Some of the successful measures to
curb smoking include raising government taxes,
restricting smoking in the workplace and public
places, and banning advertising and sponsorship
by tobacco companies.
The implementation of national programmes
which focus upon primary prevention is
essential. Economies of scale can potentially be
achieved by linking or integrating programmes.
Examples include programmes relating to
environmental pollution, public transport
services, urban planning and architecture.The
WHO concept of the ‘Healthy City’ applies
with great force to primary prevention
programmes.
Factors which hamper success include the
hostile modern environment (particularly in
urbanized settings), the impact of consumerism,
the interest of multinational companies and
socio-economic pressures.
A healthy, balanced diet (less fat, salt, refined
sugar, alcohol and calories; more fibre, fruit
and vegetables)
Regular physical activity (eg aerobic
exercises)
A healthy social life and relaxation
techniques to combat stress
Smoking cessation
Sustained weight loss in the overweight
Table 18: Lifestyle behaviour to be promoted
Preventing Cardiovascular Disease
Cardiovascular disease prevention in people
with diabetes should in the first place be part
of a comprehensive approach to prevention in
the whole community. It is inevitably easier for
people with diabetes to change lifestyle
behaviour if this is occurring in the population
at large.There should be national guidelines on
lifestyle modification leading to an overall
healthier population, with particular emphasis
on people with diabetes.These kinds of
activities tend to be more successful when
based on local initiatives (ie the bottom-up
approach). Such initiatives are being promoted
by IDF and WHO.

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