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Page 1: Stay Aware!

Diabetes andCardiovascular Disease:

Time to Act

The mission of the IDF is to work with our member associations to enhance the livesof people with diabetes.

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© International Diabetes Federation, 2001No 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 Office1 rue Defacqz

B-1000 BrusselsBelgium

Tel: +32 2 5385511Fax: +32 2 5385114e-mail: [email protected]://www.idf.org

ISBN: 2-930229-15-2

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Acknowledgements

The International Diabetes Federation (IDF) would like to thankMerck, 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 ofthe Diabetes and Cardiovascular Disease Editorial Committee:

Clive Cockram (Chair)George AlbertiBjørnar Allgot

Abdullah Al NakhiPablo Aschner

Terrence DwyerSteve Haffner

Jean-Claude MbanyaCara McLaughlin

Viswanathan MohanCorby ShugarsKelly Stoddard

Special thanks also to Kristen Hynes from the Menzies Research Centre, Australia, forher help with the mortality figures in Chapter 2.

Editor and project manager: Cara McLaughlinProject coordinator: Stefania Sella

Project support for mortality data: Lala Rabemananjara

Design and layout: perplex | Aalst, BelgiumPrinting: Imprimerie L Vanmelle SA, Gent/Mariakerke, Belgium

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Diabetes and Cardiovascular Disease: Time to ActI 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

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ContentsPreface: A Time Bomb 7

Introduction 9

Executive Summary 11

Chapter 1: Diabetes 13Classification 13Risk Factors 14The Extent of the Problem 14Future Outlook 16

Chapter 2: Cardiovascular Disease 19The Cardiovascular Disease Triad 19The Extent of the Problem 22

Chapter 3: Diabetes and Cardiovascular Disease: Double Jeopardy 37The Extent of the Problem 37A Costly Situation 37How does Diabetes Lead to Cardiovascular Disease? 37The Cardiovascular Disease Triad in Diabetes 40The Vicious Cycle 43

Chapter 4: Risk Factors 45What is a Risk Factor? 45Cardiovascular Risk Factors 45Diabetes and Other High Blood Glucose Conditions: A Major Risk Factor 46Conclusion 51

Chapter 5: Reducing the Risks 53Management of Risk Factors in the General Population 53Management of Risk Factors in People with Cardiovascular Disease 55Management of Risk Factors in People with Diabetes 55National Approaches to Prevention: Lifestyle 57

Chapter 6: Treatment of Cardiovascular Disease in Diabetes 59Treatment of Coronary Heart Disease 59Treatment of Cerebrovascular Disease 60Treatment of Peripheral Vascular Disease 60Conclusion 60

Conclusion: The Way Forward 61

Fact File 63

Contents

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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

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A Time Bomb

A Time BombP R E F A C E

Diabetes is closely associated with cardiovascular disease and therefore an increased risk ofheart attack, stroke and amputation of the lower limbs. Indeed, heart attack and stroke arethe 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 toresult in an explosion of these and other cardiovascular complications - unless preventive action istaken now.

Such action includes striving to prevent diabetes itself and, when diabetes is present, to prevent ordelay cardiovascular risk factors in people with the condition. Both these objectives can beachieved by common strategies, such as promoting healthy lifestyles, educating healthcareprofessionals and raising public awareness. What is more, these steps can also help prevent theonset of cardiovascular disease in the general population.

All should pay heed – policy makers, the healthcare team and, above all, the public. We truly hopethat you take the messages spelt out in this publication to heart. IDF considers cardiovasculardisease to be one of the most serious problems facing people with diabetes, and intends to leadthe fight against it from the front. This is just the beginning!

Professor Sir George AlbertiIDF President

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Introduction

Introduction

Aims of the Book

Diabetes and Cardiovascular Disease: Time to Actis the most up-to-date report on globalcardiovascular disease and diabetes. Theobjectives of this publication are to raiseawareness of the close link between these twodiseases and to recommend courses of actionto prevent or delay the cardiovascularcomplications of diabetes.

Who Is It for?

This publication seeks to inform healthcaredecision makers of the huge public healthburden posed by cardiovascular disease inpeople with diabetes, and to point to thepossibilities of and urgent need for prevention.IDF’s member associations are encouraged tomake use of this book to lobby theirgovernments for investment in preventivestrategies.

Diabetes and Cardiovascular Disease: Time to Actcan also be used as a tool for sensitizinghealthcare professionals to the need for anaggressive management of all cardiovascularrisk factors in people with diabetes.

This publication is also a source of backgroundinformation for member associations’ publicawareness campaigns (the theme of WorldDiabetes Day 2001 being ‘Reducing the Burden:Diabetes and Cardiovascular Disease’).

Finally, anyone with an interest in learning moreabout diabetes and/or cardiovascular diseasecan consult this publication.

How Should this Book Be Used?

Chapter 1 sets the scene by giving somebackground information on diabetes. Moredetailed information about diabetes can befound in other IDF publications such asDiabetes Atlas 2000 and Diabetes Slide Show.

Chapter 2 defines cardiovascular disease anddiscusses its various clinical manifestations.It also provides the most recent globalmortality data for coronary heart diseaseand cerebrovascular disease.

Chapter 3 looks at cardiovascular disease inthe setting of diabetes. For those readingthis as a stand-alone chapter, there arecross-references to Chapter 2 forbackground explanations of the clinicalmanifestations of cardiovascular disease.

Chapter 4 examines the risk factors forcardiovascular disease. It focuses ondiabetes as one of the major cardiovascularrisk factors.

Chapter 5 describes how cardiovascular riskfactors can be managed, both in the generalpopulation and in people with diabetes.Again, to put the information in context forthose reading this as a stand-alone chapter,there are cross-references to Chapter 4.

Chapter 6 reviews the treatment possibilitiesfor established cardiovascular disease inpeople with diabetes.

Readers who are unfamiliar with the medicalterminology can make use of the glossary.Terms included in the glossary are printed inbold when first used in the text.

The studies of diabetes and heart diseasewhich are referred to in the text are explainedin more depth in Annex 4. The first referenceto each of these studies is printed in italics.

The research on which Diabetes andCardiovascular Disease: Time to Act is based isdocumented in the bibliography.

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Executive Summary

Executive Summary

Diabetes

Diabetes mellitus is a chronic disease whichhas been described as a state of raised bloodglucose associated with premature mortality. Itarises when the pancreas fails to produceenough insulin (type 1 diabetes), or when thebody cannot effectively make use of the insulinproduced (type 2 diabetes).

Diabetes is fast becoming a world pandemic.Although there is no evidence that type 1diabetes is preventable, it is clear thatmodifiable factors exist for type 2 diabetes. Ifaction is not taken to stem the tide of type 2diabetes, the prospects for world health arebleak.

Cardiovascular Disease

Cardiovascular diseases are diseases affectingthe heart and circulatory system, which, forexample, can result in heart attack, stroke andamputation of the lower limbs.

Cardiovascular disease is a major worldwidepublic health problem. It is the number onecause of death in industrialized countries. It isalso set to overtake infectious diseases as themost common cause of death in many parts ofthe less developed world, with levels becomingcomparable to those in Western societies – asituation which seemed inconceivable a fewdecades ago.

Diabetes and CardiovascularDisease: Double Jeopardy

Diabetes can lead to cardiovascular damage ina number of ways. The processes do not

develop independently, as each may accelerateor worsen the others. Thus, as diabetesprogresses, the heart and blood vessels areexposed to multiple attacks. The cardiovascularcomplications of diabetes are therefore a majorcause of illness, death and healthcare costs.

Cardiovascular death rates are either high orappear to be climbing in countries wherediabetes is prevalent. When we consider thatthe number of people with diabetes around theworld is predicted to double over the comingdecades, the outlook for cardiovascular diseasebecomes even more alarming. The recentdecline in cardiovascular disease in the USA,Australasia and western Europe may becompromised significantly by this upsurge indiabetes. In other parts of the world wherecardiovascular disease has been proliferating inrecent years, the additional impact of diabetesthreatens to have devastating consequences.

In short, the predicted escalation in diabetesprevalence is likely to contribute to acardiovascular disease epidemic, particularly inthe developing world - unless preventivemeasures are taken as a matter of urgency.

Risk Factors

Because of the soaring prevalence of diabetesworldwide, it now rivals smoking, high bloodpressure and lipid disorders as a major riskfactor for cardiovascular disease. Diabetes alsobelongs to a special risk category as it somarkedly increases the risk of cardiovasculardisease.

People with diabetes have a higher prevalenceof many of the other common cardiovascularrisk factors than the general population. What

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is more, most of these cardiovascular riskfactors have a more harmful effect in thepresence of diabetes.

Many people with diabetes have numerous riskfactors. This fact becomes even more seriousconsidering that the presence of several riskfactors has a multiplicative and not just anadditive effect.

Due to the higher prevalence and impact ofcardiovascular risk factors, as well as the roleof hyperglycaemia, people with diabeteswithout overt cardiovascular complicationsmerit an intervention against risk factors whichis as aggressive as that which would normallybe provided for individuals with establishedcardiovascular disease.

Reducing the Risks

Many cardiovascular deaths are potentiallypreventable in both people with and withoutdiabetes if we can systematically addressknown risk factors. While some risk factors arefixed (such as age, gender and geneticbackground), many others are modifiable, suchas high blood pressure, lipid abnormalities,obesity and smoking.

As many people with diabetes who experiencea first coronary event die prior to getting tohospital, they cannot benefit from secondaryprevention strategies. Therefore themanagement of risk factors in people withdiabetes should precede the onset ofcardiovascular disease.

The cardiovascular risk factors specific todiabetes have been identified by many recentstudies and it has been proven possible toreduce their impact dramatically. These positiveresults call for aggressive action to be taken totreat the risk factors that are common inpeople with diabetes. However suchapproaches are frequently not implemented inclinical practice. There is therefore a clear needfor greater awareness of treatment possibilitiesamong healthcare professionals.

Lifestyle modification (including healthy eatinghabits, regular physical exercise, smokingcessation and sustained weight loss in theoverweight) can be of major benefit inpreventing non-communicable diseases such asdiabetes and cardiovascular disease. On thenational level, cardiovascular disease preventionin people with diabetes should in the first placebe part of a comprehensive approach toprevention in the whole community. It isinevitably easier for people with diabetes tochange lifestyle behaviour if this is occurring inthe population at large.

Treatment

Many of the treatment methods forcardiovascular disease are similar irrespectiveof whether diabetes is present or not.However specific issues related to diabetesinclude the difficulty of diagnosing ‘silent’cardiovascular disease, the need for theaggressive management of all risk factors, andthe use of insulin therapy to achieve bloodglucose control when a heart attack occurs.

Since there are many risk factors involved, thetreatment and follow-up of cardiovasculardisease in people with diabetes can be acomplicated, time-consuming and expensiveprocess. Hence the value of preventivemeasures cannot be overemphasized.

The Way Forward

The good news is that it is possible to slow orstop the consequences of cardiovasculardisease in diabetes. Action must be taken onfour levels – prevention, treatment, educationand research. There can be no doubt that nowis the time to act.

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DiabetesDiabetes mellitus is a chronic disease whichhas been described as a state of raised bloodglucose (hyperglycaemia) associated withpremature mortality. It arises when the betacells in the pancreas fail to produce enoughof the hormone insulin, or when the bodycannot effectively use the insulin produced.

Pancreas

Kidneys

Stomach

Figure 1: The pancreas

Failure of insulin secretion, action or both leadsto raised blood glucose and other metabolicchanges which, if uncontrolled, can causeserious complications. The most important ofthese are retinopathy (affecting the eyes),nephropathy (affecting the kidneys),neuropathy (affecting the nerves) andcardiovascular disease (affecting thecirculatory system).

Classification

One problem over the years has been theclassification of diabetes into differentcategories. Most recently, a World HealthOrganization (WHO) Consultation and theAmerican Diabetes Association (ADA) ExpertCommittee have divided diabetes into fourmain types (Table 1).

What was previously known as insulin-dependent diabetes mellitus (IDDM) hasbecome 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 insulinproduced by the body as a result of beta cell destruction.

2 Type 2 diabetes • Characterised by disorders of both insulin action orsecretion, either of which may predominate, but both ofwhich are usually present. Usually controlled by diet,exercise and oral hypoglycaemic agents. Insulin may berequired for metabolic control.

3 Other specific types of diabetes • Other types of diabetes where the cause is known (eggenetic 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

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classification, and non-insulin-dependentdiabetes mellitus (NIDDM) is now type 2diabetes.

At present the diagnosis of type 2 diabetes isone of exclusion, that is, it is not one of theother types. There are undoubtedly manydifferent causes with a lot of as yet unknowngenes involved. As we find out more aboutthese, movement of people from the ‘type 2’category into the ‘other specific types’category will occur.

Lesser degrees of abnormal glucose levels arealso recognized. These include impairedglucose tolerance (IGT), blood levels thatare higher than normal but below the level ofsomeone with diabetes, and impaired fastingglycaemia (IFG), raised fasting levels ofglucose. IGT is now considered a risk categoryrather than a type of diabetes per se, and IFGis a new risk category. Both IGT and IFGrepresent a risk of 25% to 50% of developingdiabetes in the next 10 years, but areparticularly amenable to lifestyle interventions.

The other major offshoot of the newclassification is the metabolic syndrome.This reflects the clustering of type 2 diabetesor IGT with several other major cardiovasculardisease risk factors, such as central obesity,abnormal levels of lipids (dyslipidaemia), highblood pressure (hypertension), insulinresistance and a slightly increased output ofprotein 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 riskstates are provided in Annex 1.

Risk Factors

No clear-cut modifiable risk factors have beenidentified for type 1 diabetes. The risk factorsfor type 2 diabetes are shown in Table 3.

Certain ethnic groups seem particularlysusceptible to the development of diabetes.Examples include Amerindians, Pacific islandcommunities, South Asians, Australianaborigines, African-Americans and Hispanics.There is also a strong association with age andfamily history. For instance, it has beenestimated that if you have a sibling or parentwith type 2 diabetes, you have a 40% lifetimerisk of developing it yourself. These risk factorscannot be altered. However, most of the recentupsurge in diabetes is lifestyle related. Thedramatic rise in prevalence is closely associatedwith a lack of physical activity, obesity(particularly central obesity) and a change to‘Western’-style diets. These changes, togetherwith urbanization and mechanization, appear tobe inevitable accompaniments ofmodernization.

• 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 ProblemDiabetes is becoming a world pandemic. Bothtype 1 and type 2 diabetes are spreadingrapidly across the globe (Figure 2). Type 1diabetes accounts for less than 10% of the totaland is a particular problem in young northernEuropeans. It should be stressed however thatit can occur at any age, and that there are asmany people in the world with type 1 diabetesover the age of 20 years as there are under theage of 20.

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Figure 2: Prevalence estimates of diabetes mellitus, IDF Regions, 2000Source: International Diabetes Federation (2000)

No

data

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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 thereare at least 150million people in theworld with diabetesnow. This figure isexpected to doubleover the next 25years. The predictedincrease is moststriking in India andChina, but no part ofthe world is spared. In

addition to these alarming absolute rises innumbers, there is also a worsening trend forthe disease to affect younger age groups. In

developed countries the sharpest increasesaffect the over 65s, unlike the situation indeveloping countries where most new casesare occurring in those between 44 and 65years of age. In all parts of the world type 2diabetes is also now emerging in children andadolescents, thereby raising the threat of onsetof all complications at an earlier age.

Future Outlook

Although there is no evidence that type 1diabetes is preventable, it is clear thatmodifiable factors exist for type 2 diabetes. Ifaction is not taken to stem the tide of type 2diabetes, 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 Guinea 1

2

3

4

5

6

7

8

9

10

Mauritius

Bermuda

British Virgin Islands

Grenada

St Kitts and Nevis

Hong Kong SAR, PRC

Cayman Islands

Table 4: ‘Top ten’ countries for diabetes prevalenceSource: International Diabetes Federation (2000)

It is estimated thatthere are some150 million peoplein the world withdiabetes now. Thisfigure is expected todouble over the next25 years.

Fact

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national health resources in many countries.Can the pandemic be prevented? The answer isyes – but only with a high degree of dedicationand commitment. Experimental studies inChina, Tanzania, Finland and Sweden haveproven that lifestyle modification can slow thedevelopment of diabetes in high-risk groups.But a concerted world effort spearheaded byWHO, IDF and its national associations isneeded to bring the message home. Put assimply as possible, the message to betransmitted is: ‘Eat Less, Walk More’.

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Cardiovascular DiseaseCardiovascular diseases are diseases affectingthe heart and circulatory system. In developingcountries the most common cause ofcardiovascular disease used to be infection ofthe heart valves. However, in recent years therehas been a shift away from infectious causes inmany developing nations. Today the mostwidespread form of cardiovascular diseasearound the world is that which starts withdamage to the blood vessels.

The two main processes by which the bloodvessels become damaged are atherosclerosisand hypertension:

1. Atherosclerosis leads to the formation ofplaques of atheroma which narrow thediameter of the large and medium-sizedarteries. This narrowing of the arteriesimpairs blood flow. Plaques are also proneto rupture or to ulcerate and then act as asite for blood clot formation. The resultingblood clots, which can block the affectedvessel completely, are usually responsible forthe more severe clinical manifestations ofcardiovascular disease such as heartattack and stroke.

2. Hypertension damages the smaller vessels inthe circulatory system. Over time theybecome scarred, hardened, narrowed andless elastic. Hypertension can also bothpredispose to and accelerate thedevelopment of atherosclerosis.

The Cardiovascular Disease Triad

The major clinical manifestations ofcardiovascular disease can be divided intothree groups:

• those affecting the heart and coronarycirculation (coronary heart disease);

• those affecting the brain and cerebralcirculation (cerebrovascular disease); and

• those affecting the lower limbs (peripheralvascular disease).

Lower limbs(peripheralvascular disease)

Brain and cerebral circulation(cerebrovascular disease)

Heart andcoronarycirculation(coronaryheartdisease)

Figure 3: The cardiovascular disease triad

Cardiovascular DiseaseC H A P T E R 2

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Coronary Heart Disease

The heart receives a blood supply of its ownfrom the blood vessels known as thecoronary arteries. The principalmanifestations of coronary heart diseaseinclude the chronic form resulting from thenarrowing of the coronary arteries - angina -or the acute forms resulting from the blockingof the coronary arteries - heart attack orsudden death. Heart failure is a likelyaccompaniment of coronary heart disease ineither the short or long term.

Leftcoronaryartery

Aorta

Rightcoronaryartery

Figure 4: The heart

Angina: This term is used to describe pain in thechest due to a reduced blood supply to theheart (ischaemia). It results fromatherosclerosis in the coronary circulation.Typically angina causes central chest pain, whichoften radiates to the left arm, shoulder or jaw.The pain is related to exertion and is relievedby rest. Shortness of breath and sweating are

commonly associated with angina. If theresponsible plaque of atheroma is causing asevere narrowing of the vessel, then anginasymptoms may rapidly worsen and occur atrest, and may warn of an impending heartattack.

Heart attack: Atherosclerosis can lead to aheart attack if the coronary arteries becomeblocked. The onset of a heart attack is usuallyheralded by severe central chest pain, whichmay also radiate to the left arm, shoulder orjaw. Severe shortness of breath, sweating andfeeling faint are common additional symptoms.

Sudden death: Sudden death can occur as aconsequence of an abrupt loss of the heart’sability to pump blood. It may result from amassive heart attack or a severe abnormality ofthe rhythm of the heartbeat.

Heart failure: This occurs when damage to theheart muscle is severe enough to prevent itfunctioning adequately as a pump. It manifestsitself either acutely with severe shortness ofbreath or, more chronically, with shortness ofbreath, reduced exercise tolerance and swellingof the ankles.

Cerebrovascular Disease

The brain receives its blood supply from fourmain arteries: the two carotid arteries andthe two vertebral arteries. The clinicalconsequences of vascular disease in thecerebral circulation will depend upon whichvessels 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

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Vertebralartery

Carotidartery

Figure 5: The brain

The following situations can occur:

Stroke: Stroke occurs when the blood supply toa part of the brain is blocked resulting in thedeath of an area within the brain. If a largevessel is blocked the outcome may be rapidlyfatal or may lead to very severe disability. Ifsmaller blood vessels are blocked the outcomeis less critical and recovery may be good. Themost common types of disability are the loss ofuse of one side of the body and speechproblems.

There are three principal types of stroke:• Thrombotic: Stroke due to the blockage of

an artery leading to or in the brain by ablood clot.

• Haemorrhagic: Stroke due to bleeding froma ruptured blood vessel, usually aconsequence of hypertension.

• Embolic: Stroke due to the formation of ablood clot in a vessel away from the brain.The clot is carried in the bloodstream untilit lodges in an artery leading to or in thebrain.

The thrombotic and haemorrhagic forms arethe most common, although they occur withvarying frequency in different parts of theglobe.

Transient ischaemic attack: Transient ischaemicattacks arise when the blood supply to a part

of the brain is temporarily interrupted withoutproducing permanent damage. By definition,recovery occurs within 24 hours. These attacks,particularly if frequent, can be a warning sign ofan impending stroke. They usually result fromsmall blood clots or clumps from plaques ofatheroma which get carried into the bloodcirculation producing transient blockages.Occasionally these clots may get carried fromthe heart or arteries leading to the brain (egcarotid arteries), rather than from within thecerebral circulation itself.

Dementia: This may result from repeatedepisodes of small strokes which produceprogressive damage to the brain over a periodof time. The main clinical feature of dementia isa gradual loss of memory and intellectualcapacity. Loss of motor function in the limbsand incontinence can also occur.

Peripheral Vascular Disease

The lower limbs each receive their bloodsupply via an artery known as the femoralartery. Peripheral vascular disease is said to bepresent when the blood vessels in this part ofthe body are affected by atherosclerosis. In theabsence of diabetes the single most importantrisk factor is heavy cigarette smoking.

Femoralartery

Figure 6: Lower limbs

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The following situations can occur:

Gangrene: The term gangrene is used todescribe the death of tissue due to a loss ofblood supply. Severe gangrene can occur as aresult of the blockage of a large blood vessel.

Intermittent claudication: This term describespain, usually in the calves when walking, and isdue to an impaired blood supply to the calfmuscles. As with angina, the pain is usuallyrelieved by resting, but if the situation worsenspain at rest can also occur.

The Extent of the Problem

Cardiovascular disease is a major worldwidepublic health problem. It is the number one

cause of death inindustrialized countries.It is also set toovertake infectiousdiseases as the mostcommon cause ofdeath in many parts ofthe less developedworld, with levelsbecoming comparableto those in Westernsocieties – a situationwhich seemedinconceivable a fewdecades ago.

The manifestationsvary between different

ethnic groups. For example, while Caucasianpeople are particularly prone to disease of thecoronary circulation, Chinese, Japanese andAfrican people are more prone to disease ofthe cerebral circulation. Studies among migrantpopulations, such as Japanese people living inthe USA, suggest that these differences may bedue more to variations in external risk factorssuch as diet than to differences in the genes ofthe people themselves.

Coronary Heart Disease

Data on the incidence of coronary heartdisease are now available for many developedcountries through the WHO-sponsoredMONICA Project, but unfortunately such dataare not available for developing nations.Consequently, to obtain an idea of the globaldistribution of the disease it is necessary toexamine the available mortality data.

The data in Tables 6 and 7 and Figures 7 to 14reflect the most recent mortality rates forcoronary heart disease. However substantialchanges have taken place over time. In somedeveloped nations where rates were extremelyhigh by world standards - including the US,many western European countries andAustralasia - mortality has plunged by as muchas 50% in the last 30 years. In other developedcountries where rates were low, such as Japan,the mortality has remained low. In others,particularly in eastern Europe, rates have beenclimbing. In many developing nations,particularly in the Pacific and the Middle East,rates have risen to those previously found onlyin the West. On the whole, these trends reflectchanges in the prevalence of the risk factors(see Chapter 4). For example, there has been adecline in cholesterol levels in the US andother previously high-risk countries such asFinland. Population-based levels of treatmentfor hypertension and a decrease in smokingprevalence have also occurred in many of thecountries which have witnessed a reduction incoronary heart disease mortality. Availability oftreatment for established disease has alsoimproved.

Cerebrovascular Disease

The data in Tables 8 and 9 and Figures 7 to 14provide information on cerebrovascular diseasemortality from all types of stroke. It isnecessary to use mortality data forinternational comparisons because, as withcoronary heart disease, incidence data areavailable for too few countries.

Cardiovasculardisease is thenumber one causeof death inindustrializedcountries. It is alsoset to overtakeinfectious diseasesas the mostcommon cause ofdeath in many partsof the developingworld.

Fact

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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

Mortality (per 100,000 population per year)

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 alsodeclined markedly in many developed countriesduring the last half of the twentieth century. Indeveloping countries and in the former SovietUnion, rates appear to have shot up. They arecertainly much higher in many developingcountries now than in developed countries.

However historical data are lacking to confirmthese trends.

As well as a difference in total trends, there arealso differences in the relative frequencies ofthe type of stroke (see page 21) in differentparts of the world. In Japan and China for

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Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Yugoslavia*

Kazakhstan Republic

Romania

Moldova, Republic of*

Bulgaria

Latvia*

Guyana

Russia

Kyrgyz Republic

Ukraine1

2

3

4

5

6

7

8

9

10

Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Guyana

St Lucia*

Romania

Kazakhstan Republic

Yugoslavia*

Russia

Moldova, Republic of*

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 ahigher proportion of cases than is seen in theWest. The relative frequency of the thromboticform of stroke appears to mirror theprevalence of coronary heart disease. However,reliable data on the worldwide occurrence ofeach type of stroke are not available.

Peripheral Vascular Disease

Data on peripheral vascular disease prevalenceoutside the context of diabetes are scarce. It istherefore currently not possible to provideinternational comparisons of the kind preparedfor coronary heart disease and cerebrovasculardisease.

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Sources and MethodologyTables 6 to 9, Figures 7 to 14 and Annex 3provide information on coronary heart diseaseand cerebrovascular disease mortality inselected countries. The data are the latestobtainable for each country. They werecompiled for Diabetes and CardiovascularDisease: Time to Act by the WHO CollaboratingCentre at the Menzies Research Centre,University of Tasmania, Australia.

The source of data for all countries (exceptAmerican Samoa, Canada, Cook Islands, Fiji,Northern Mariana Islands, Palau, Taiwan, andTanzania) was the Global CardiovascularInfobase website (http://cvdinfobase.ic.gc.ca/)of the WHO Collaborating Centre in Ottawa,Canada. This website uses data from the WorldHealth Statistics Annual, World HealthOrganization, Geneva (1985, 1987, 1988, 1989,1990, 1991, 1992, 1993, 1994, 1995 and 1996editions).• Data for American Samoa were provided by

the Medical Records Office, LBJ MedicalCenter (the ‘Causes of Death’ report whichextracts data from death certificates fromthe Department of Health’s Office of VitalRecords).

• Data for Canada came from the HealthStatistics Division, Statistics Canada 1999.

• Data for the Cook Islands were provided bythe Medical Records Unit of the Ministry ofHealth.

• Data for Fiji were provided by the Ministryof Health and Social Welfare’s mortalitydatabase which draws on two sources:medical certificates (Cause of Death) andConsolidated Monthly Return.

• Data for the Northern Mariana Islands wereprovided by the Office of Health andPlanning Statistics of the Department ofPublic Health (data from death certificates).

• Data for Palau were provided by theDepartment of Health’s Vital StatisticsDatabase which contains data from thedeath registry.

• Data for Taiwan were from the Departmentof Health’s Office of Statistics.

• Data for Tanzania were extracted from:Walker RW, et al (2000).

All data have been age-standardized across theage range of 35-74 years using the worldstandard population. Age-standardization wascalculated from data available on the GlobalCardiovascular Infobase website in January2001, with the following exceptions:• Age-standardized rates for ages 35-74 for

American Samoa (coronary heart disease),Fiji (coronary heart disease andcerebrovascular disease) and NorthernMariana Islands (coronary heart disease andcerebrovascular disease) are estimationscalculated using rates for ages 35-64published in Profile of Cardiovascular Diseases,Diabetes Mellitus and Associated Risk Factorsin the Western Pacific Region. MenziesResearch Centre and World HealthOrganization Regional Office for theWestern Pacific, 1999.

• Age-standardized rates for ages 35-74 forBrazil (coronary heart disease andcerebrovascular disease) were estimatedusing the age-standardized rates for ages35-64 calculated using data from the GlobalCardiovascular Infobase website.

Note: Coronary heart disease for the CookIslands consists of heart attack only (acutemyocardial infarction; InternationalClassification of Diseases code ICD9: 270 BasicTabulation List).

The data have been organized according to theseven IDF Regions: Africa, EasternMediterranean and Middle East, Europe, NorthAmerica, South and Central America, SouthEast Asia and Western Pacific. Data are notavailable for all IDF member countries.Countries marked with an asterisk are not IDFmembers.

Estimations of diabetes prevalence (20-79 agegroup) are also provided in Annex 2 and belowthe charts in Figures 7 to 14 where available.These data come from: International DiabetesFederation (2000).

– = No data available.

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Figure 7: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

2512– –

Botswana*

121

160

90

56

Seychelles*

88 85 83

41

South Africa

5639

616

Zimbabwe

80 73

21 30

São Tomé and Príncipe*

171142

Tanzania

4.0%

1.0%

0.9%

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

Africa

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Figure 8: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

3522

111

353

Kuwait493524

62

Egypt

3817

121

205

Bahrain

9.3%

7.0%

14.8%

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

Eastern Mediterranean and Middle East

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Figure 9: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

Belgium

5235

138

43

France

4122

89

22

Hungary

213

118

436

159

Greece

7858

166

49

Germany

6139

215

72

Italy

6038

141

39

6549

370

127

Ireland, Republic of

6540

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)

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Finland

7647

316

86

Israel

5739

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*

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Figure 10: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

6447

232

113

Malta

53 48

153

45

Luxembourg

5536

245

74

Norway

4835

178

58

Netherlands

147

84

117

42

Portugal

5632

91

31

Spain

5946

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%

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

Europe (2)

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[ 31 ]

149

102

566

200

Lithuania344

214

688

236

Russia

107

65

259

77

Poland

4830

219

65

Sweden

458

312

504

220

Ukraine

223

170

658

352

Turkmenistan*

41 349 3

Turkey272

209

351

128

Yugoslavia*

196

158

209

86

Macedonia

282

225

592

368

Moldova, Republic of*

280

194

351

155

Romania

145122

267

161

Tajikistan*197

153

454

291

Uzbekistan*

– 5.5% 0.3%

4.5%

6.4%

5.7%

3.2%

3.5%

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[ 32 ]

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

42 32

224

90

United States of America

56 48

127

67

Mexico

11998

133108

Belize

177160

89

54

Jamaica

312

182180

46

Guyana

143

77

208

83

Bahamas

184

123

374

227

Trinidad and Tobago

108129

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

Figure 11: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

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Paraguay

ArgentinaChile

Cuba

Guatemala

Nicaragua

Panama

Peru

Suriname

Uruguay

Venezuela

Colombia

Dominican Republic

Puerto Rico

24 3043

25

7347

96

56

61 496240

85 77

222

134

45 4157

33

4322

170

69

82 76

173

100

9475

223

110

88 80

219

103

11996

123

61

107

74

181

65

122

68

140

39

96

59

121

49

23 202814

8.6%

2.9%

El Salvador

58 4665

40

4.8%

Costa Rica

5340

145

84

3.4%

2.9%

Ecuador

554135

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%

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

South and Central America

Figure 12: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

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248

139

371

181

Mauritius

4424

92

25

Sri Lanka

2.9%

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

15.0%

South East Asia

Figure 13: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

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Figure 14: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetesprevalence

225

150

7651

China, Peoples' Republic of

10287

242

114

Singapore, Republic of111

63

125

58

Philippines

34 29

164

73

Australia

153

114

181

98

Mongolia*

2.7%

191

121

3814

Korea, Republic of

6.1%

734145

16

Japan

7.4%

6547

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

2551

Taiwan

9.1%

11.3%

male (per 100,000 population/year)

female (per 100,000 population/year)

Cerebrovascular disease mortality

male (per 100,000 population/year)

female (per 100,000 population/year)

Coronary heart disease mortality

prevalence (%)

Estimated diabetes prevalence 0.0

American Samoa*

317

256

152

41

37

214

3748

Palau*

9.1%

Fiji*

177

479

66

100

Northern Mariana Islands*

7756

174

0

Cook Islands*

129149

0

228

12.1%

Western Pacific

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Double Jeopardy

Diabetes and CardiovascularDisease: Double Jeopardy

C H A P T E R 3

The Extent of the Problem

In the previous two chapters we saw theextent of both diabetes and cardiovasculardisease amongst the general population. Thischapter brings the two diseases together and

addresses specificallythe topic ofcardiovascular diseasein the setting ofdiabetes.

People with diabetesare two to four timesmore likely to developcardiovascular diseasethan people without

diabetes, making it the most commoncomplication of diabetes. The data presented inChapter 2 show that cardiovascular death ratesare either high or appear to be climbing incountries where diabetes is prevalent. Whenwe consider that the number of people withdiabetes around the world is predicted todouble over the coming decades, the outlookfor cardiovascular disease becomes even morealarming.

The recent decline in cardiovascular disease inthe USA, Australasia and western Europe maybe compromised significantly by this upsurge indiabetes. In other parts of the world, wherecardiovascular disease has been proliferating inrecent years, the additional impact of diabetesthreatens to have devastating consequences.

In short, the predicted escalation in diabetesprevalence is likely to contribute to acardiovascular disease epidemic, particularly inthe developing world - unless preventivemeasures are taken as a matter of urgency.

A Costly Situation

Diabetes is already consuming up to 10 percentof total national healthcare budgets in manycountries. About half of this expense can beattributed to the costs of managing diabetescomplications. As reflected in the patterns ofhospital admissions for the treatment ofcomplications, cardiovascular complicationsaccount for the bulk of this (Figure 15). It istherefore clear that the current situation hasenormous implications in both human andeconomic terms.

The public health impact of cardiovasculardisease in diabetes is exacerbated by thefollowing factors:• Type 2 diabetes is occurring at an earlier

age, thereby precipitating the threat of thepremature onset of cardiovascularcomplications.

• The discovery of insulin has extended thelife expectancy of people with type 1diabetes significantly. Each year of prolongedlife brings about a greater risk ofcardiovascular complications.

How does Diabetes Lead toCardiovascular Disease?

All types of diabetes can lead to diseaseswithin the heart and circulatory system in anumber of ways. In many people with diabetesthese different factors co-exist, resulting inprogressive damage to the heart and bloodvessels.

As we saw in the previous chapter (page 19),the two main processes which lead tocardiovascular disease are atherosclerosis andhypertension.

People withdiabetes are two tofour times morelikely to developcardiovasculardisease than peoplewithout diabetes.

Fact

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1. AtherosclerosisNot only are people with diabetes at increasedrisk of developing atherosclerosis, but theprocess also tends to be accelerated, moresevere and more widespread. This can causeserious clinical consequences in youngerindividuals. Since atherosclerosis damages themedium and large blood vessels, the termmacroangiopathy is often used to indicate itspresence in people with diabetes.

Atherosclerosis in diabetes results from acomplex interplay between a number of riskfactors. These are described in more detail inChapter 4.

2. HypertensionHypertension is at least twice as common inpeople with diabetes as in the generalpopulation, and is also more frequent in peoplewith impaired glucose tolerance.

As well as atherosclerosis and hypertension, thereare other damaging effects which are specific todiabetes: microangiopathy, autonomicneuropathy and other abnormalities of theblood vessels. These processes worsen vascularfunction and therefore make the consequences of

atherosclerosis/macroangiopathy and hypertensionmore difficult to withstand. In addition, they leadto other diabetic complications such asnephropathy and impotence.

3. MicroangiopathyMicroangiopathy refers to damage to the smallblood vessels and capillaries, and is largelyrestricted to people with diabetes. It is a directresult of chronic hyperglycaemia. Other factorssuch as hypertension and dyslipidaemia alsocontribute.

The causal link between hyperglycaemia andmicroangiopathy has been emphasized by anumber of recent clinical trials, all of which showthat the microangiopathic complications ofdiabetes are the most readily preventable withgood glycaemic control. The largest of thesestudies are the Diabetes Control and ComplicationsTrial (DCCT) in type 1 diabetes and the UnitedKingdom Prospective Diabetes Study (UKPDS) in type2 diabetes.

Microangiopathy adversely affects capillaryfunction leading to a shortage of supply of oxygenand nutrients to the tissues, and a leakage ofproteins into the tissue spaces. Capillaries

Neuropathy

Kidney disease

Total cardiovascular disease Acute complicationsOther

United Kingdom

Eye disorders

Figure 15: Proportion of hospital bed days used for the treatment of diabetic complicationsSource: International Diabetes Federation (1999)

Argentina

All microvascular Other acuteCardiovascular diseaseInfections

Other

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throughout the body are affected, but damage tothe microcirculation of the eyes, kidneys andnerves is responsible for the major clinicalmanifestations – retinopathy, nephropathy,neuropathy and the diabetic foot.

4. Autonomic NeuropathyDiabetes can affect different components of thenervous system. One component, known as theautonomic nervous system, provides a nervesupply to the internal organs of the body, includingthe heart and blood vessels. Damage to thissystem is known as autonomic neuropathy.

Damage to the autonomic nervous system can bea direct result of chronic hyperglycaemia or, inturn, can follow microangiopathy involving thesmall vessels which supply blood to the nervesthemselves, thereby causing a vicious cycle ofnerve and blood vessel damage. Damage to thenerve supply of the heart affects the regulation ofthe pulse rate. In the blood vessels, manifestationssuch as a fall in blood pressure on standing orexercising can produce disabling symptoms andcan affect measures aimed at treatinghypertension. Loss of the nerve supply to smallblood vessels can also impair the regulation ofblood flow. This is an important contributoryfactor to the development of diabetic footulcers. Autonomic neuropathy is an importantcause of impotence in men with diabetes. It canalso affect the function of the bladder, stomachand intestine.

Autonomic neuropathy Microangiopathy

Nephropathy

Heart ratedisturbances

Posturalfall inblood

pressure

Diabetic foot

Retinopathy

Neuropathy

Gastro-intestinal

dysfunction

Impotence

Dysfunctionof bladder

Figure 16: Clinical outcomes of microangiopathyand autonomic neuropathy

Microangiopathy Autonomic neuropathy Other blood vessel damage

• Damage to small • Damage to the nerve • Damage to the innerblood vessels and supply of the internal or outer lining of bloodcapillary 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

WH

AT

IS I

T?

CL

INIC

AL

OU

TC

OM

E

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5. Other Abnormalities of Blood VesselsDiabetes can also damage blood vessel walls inother ways, which can interact with bothatherosclerosis/macroangiopathy andmicroangiopathy to aggravate the situation.

The inner lining of blood vessels known as theendothelium can be damaged, for exampleaffecting the ability of the blood vessels torelax or dilate. This may impair the regulationof the blood flow. Endothelial dysfunction is animportant component of both macroangiopathyand microangiopathy, but can also appear earlyin the course of diabetes before the onset ofdetectable vascular disease.

The outer layers of the vessel wall, composedof muscle or elastic tissue, can also bedamaged. This can impair the regulation of theblood flow and may weaken the vessel wall.

Outer lining

Middle muscle layer

Inner lining(endothelium)

Figure 17: Blood vessel

To complicate matters further, commonchronic diabetes complications such asneuropathy and nephropathy can themselveshave adverse effects on the heart andcirculation. As a result, as diabetes progressesthe heart and blood vessels are exposed tomultiple attacks, all of which can interact witheach other to produce severe consequences.

The Cardiovascular DiseaseTriad in Diabetes

In practice the most important clinicalmanifestations of diabetic vascular disease canbe divided into the same three groupsdescribed in Chapter 2: those affecting thecoronary circulation, those affecting thecerebral circulation and those affecting thelower limbs. The clinical manifestationsdescribed in Chapter 2 still apply but areparticularly severe and may be modified by thepresence of additional factors or complicationsrelated to diabetes.

Coronary Heart Disease

Angina (see page 20): When autonomicneuropathy is present,the typical pain of anginawhich is usuallyassociated withischaemia may not beexperienced, leading tosilent ischaemia. Thismay manifest itself justwith 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

CL

INIC

AL

MA

NIF

ES

TA

TIO

NS

People with type 2diabetes have thesame risk of heartattack as peoplewithout diabeteswho have alreadyhad a heart attack.

Fact

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or other more vague symptoms such as nauseaor sweating.

Heart attack (see page 20): People with type 2diabetes with no prior history of heart attackshave as great a risk of having a heart attack inthe future as people without diabetes who havealready experienced a heart attack (Figure 18).

Also, since people withdiabetes often havewidespread vasculardisease, theconsequences of aheart attack are oftenmore severe than inpeople without

diabetes, resulting in greater difficulty withemergency treatments.

When autonomic neuropathy is present, heartattacks can be ‘silent’, with an absence of chestpain and presentation with less specificsymptoms. This means that the diagnosis can

easily be overlooked and, in effect, people withdiabetes can have aheart attack withouteven realizing it.

For these and otherreasons, people withtype 2 diabetes have ahigher risk of deathfollowing a heart attack(Figure 19).

Sudden death (see page20): In diabetes, suddendeath can also resultfrom abnormalities in the heart’s rhythmprovoked by autonomic neuropathy. Men withdiabetes are subject tosudden death 50% moreoften and women withdiabetes 300% moreoften than theircounterparts withoutdiabetes of the sameage.

0

10

20

30

40

50

Inci

denc

e (%

)

People without diabetes People with diabetes

No prior heart attack Prior heart attack

Figure 18: Heart attacks in people with andwithout diabetes over a period of seven yearsAdapted from: Haffner SM, et al (1998)

0

10

20

30

40

50

Mor

talit

y (%

)

People with diabetesPeople without diabetes

Men Women

Figure 19: Deaths in people with and withoutdiabetes in the year following a first heart attackAdapted from: Miettinen H, et al (1998)

People with diabetescan have a heartattack without evenrealizing it.

Fact

People with diabeteshave a two to three-fold greater risk ofheart failurecompared to peoplewithout diabetes.

Fact

Men with diabetesare subject tosudden death 50%more often andwomen withdiabetes 300%more often thantheir counterpartswithout diabetes ofthe same age.

Fact

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Heart failure (see page 20): Heart failure is acommon complication of diabetes and againcarries a high short-term mortality rate. Indiabetes, heart failure may also occur as aconsequence of microangiopathy. People withdiabetes have a two to three-fold greater riskof heart failure compared to people withoutdiabetes.

Fainting attacks: Autonomic neuropathy can leadto fainting attacks by causing eitherdisturbances of the heart rhythm or a fall inblood pressure on standing or exertion.

Cerebrovascular Disease

Stroke (see page 21):Strokes occur twice asoften in people withdiabetes andhypertension as inthose withhypertension alone.The clinical featuresare generally similar to

those seen in people without diabetes.However the additional involvement ofmicroangiopathy in diabetes can lead to aworse outcome.

Transient ischaemicattack (see page 21):Transient ischaemicattacks (mini-strokes)occur between twoand six times morefrequently in peoplewith diabetes.

Dementia (see page 21): The additive effects ofmultiple small strokes, together withmicroangiopathy affecting the small bloodvessels to the brain, lead to an increasedlikelihood of dementia in people with diabetes.

Peripheral Vascular Disease

People with diabetes account for the majorityof cases of lower-limb amputation resultingfrom vascular disease. In fact they are 15-40times more likely to require such an

amputation compared tothe general population.The factors whichpredispose to thisgreater risk aredescribed below.

Gangrene (see page 22):Although lower-limbgangrene also occurs inpeople without diabetes, the vascular diseasewhich is particular to diabetes makes it muchmore common. Diabetic gangrene can alsoresult from disease of the smaller blood vesselsproducing localized damage, for example in thetoes. People with diabetes over the age of 70have a 70-fold increased risk of lower-limbgangrene compared topeople without diabetesof the same age.

Intermittent claudication(see page 22):Intermittent claudication(calf pain) occurs threetimes more often in menwith diabetes and almostnine times more often inwomen with diabetesthan in theircounterparts without diabetes. The presence ofextensive, severe vascular disease in diabetesmay influence the type of treatment chosenand may hamper its success (in particularsurgical treatment).

Foot ulcers: Foot ulcers can occur as a result ofeither localized gangrene (usually affecting thetoes) or diabetic neuropathy (usually arising atpressure points or weight-bearing areas of thefeet). The underlying predisposing factors aremany and complicated but the vascularcomplications of diabetes, particularlymicroangiopathy and autonomic neuropathy,are very important.

Strokes occur twiceas often in peoplewith diabetes andhypertension as inthose withhypertension alone.

Fact

Transient ischaemicattacks occurbetween two and sixtimes morefrequently in peoplewith diabetes.

Fact

People with diabetesare 15-40 timesmore likely torequire a lower-limbamputationcompared to thegeneral population.

Fact

People withdiabetes over theage of 70 have a70-fold increasedrisk of lower-limbgangrene comparedto people withoutdiabetes of thesame age.

Fact

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Figure 20: Causes of death in people with diabetes in the USAdapted from: Geiss LS, et al (1995)

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The Vicious Cycle

As we have seen, diabetes can lead tocardiovascular 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 diabetesdevelop for example a heart attack or stroke,the prognosis is worse than for people withoutdiabetes because of the vicious cycle caused bythe combined vascular abnormalities associatedwith diabetes.

Indeed, cardiovascular disease is the leadingcause of death in people with diabetes indeveloped countries (Figure 20).

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Risk Factors

Risk FactorsC H A P T E R 4

What is a Risk Factor?

A risk factor is a condition that places anindividual at risk of developing a health-relatedproblem. The term has become widely used toaddress the causes of chronic, multifactorialdiseases such as diabetes and cardiovasculardisease. A risk factor can be genetic oracquired. It may be identified as a singlemeasurement (eg a physical feature such asweight), a disease (eg hypertension) or alifestyle characteristic (eg smoking). In order tobe considered a risk factor for a disease, thecondition must be associated with that diseasein a manner which is beyond chance alone. Acausal link is therefore implied. However, a riskfactor will not necessarily always lead to thedevelopment of the disease.

A risk factor must be distinguished from a riskmarker and a disease marker. A risk marker is acondition which is associated with a higher riskof developing a disease, but the association hasnot yet proven to be causal. A disease markeris a condition which indicates that a disease isalready present.

The ultimate purpose of identifying a riskfactor is to modify it in order to prevent thedisease. If the modification of the risk factorresults in a significant reduction of the diseaseoutcome, that risk factor is a main target forintervention. If the risk factor cannot bemodified but its association with the disease isstrong (eg gender or age), it may be used toselect high-risk subjects who could benefitfrom special preventive interventions.

Cardiovascular Risk Factors

• Advancing age• Diabetes and other high blood

glucose conditions• Dyslipidaemia• Genetic background• High alcohol consumption• Hypertension• Insulin resistance• Left ventricular hypertrophy• Male gender• Menopause• Obesity• Sedentary lifestyle• Smoking

Table 12: Risk factors for cardiovascular disease inthe general population

The risk factors for cardiovascular disease inthe general population are listed in alphabeticalorder below:

Advancing age: The risk of cardiovascular diseasegrows with age. It is significantly higher in menover 45 years of age and in women over 55years of age.

Diabetes and other high blood glucose conditions: Asdescribed in Chapter 3, diabetes is closelyassociated with a greater risk of the prematureonset of cardiovascular disease.

Dyslipidaemia: Elevated blood levels of totalcholesterol and of low-density lipoprotein(LDL) cholesterol, as well as low levels ofhigh-density lipoprotein (HDL) cholesterolare risk factors for cardiovascular disease.There is a continuous relationship between thelevels and the risk. In some cases raised

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triglyceride levels in the blood are also anindependent risk factor.

Genetic background: Although the responsiblegenes have not been identified, a high risk ofcardiovascular disease may be hereditary and canbe identified in people with parents or siblingswho have a history of cardiovascular disease at apremature age (ie before 55 years of age in menand 65 years of age in women).

High alcohol consumption: Excess alcohol intakecan worsen other risk factors such ashypertension.

Hypertension: Arterial pressure above the normalrange (135mm Hg systolic and 85mm Hgdiastolic) constitutes a risk factor forcardiovascular disease. As with lipids, there is acontinuous relationship between the levels andrisk. Risk may commence at lower levels of bloodpressure in some susceptible individuals.

Insulin resistance: Recently it has been shown thatpeople with resistance to the action of insulin atthe cellular level have a greater risk ofcardiovascular disease.

Left ventricular hypertrophy: The increasedthickness of the heart’s left ventricular muscle isalso a risk factor for cardiovascular disease.Initially it is a silent condition which has to beinvestigated by cardiac tests. It is mainly presentin people with hypertension.

Male gender: Men have a higher risk ofcardiovascular disease than women of the sameage.

Menopause: Pre-menopausal women areprotected from developing cardiovascular diseasebecause the oestrogen made in their ovariesprotects their hearts. The risk of cardiovasculardisease increases in women after the menopausebecause the protective effect of oestrogen is lost.

Obesity: Excess body fat has a marked adverseinfluence on risk factors such as hypertension,dyslipidaemia, diabetes and other forms ofimpaired glucose regulation. It can be identifiedby a high body mass index (BMI). The adverse

effect of excess weight is more pronouncedwhen the fat is concentrated mainly in theabdomen (central obesity), as often happens inmen. This can be identified by a high waist/hipratio.

Sedentary lifestyle: Diminished physical activity hasbeen shown in the population at large to beassociated with an intensified risk ofcardiovascular disease.

Smoking: Cigarette smoking in particular is a riskfactor for cardiovascular disease. The risk startswith any daily amount and can be rapidlyabolished by stopping the habit.

It is important to emphasize that the presence ofmultiple cardiovascular risk factors has amultiplicative and not an additive effect upon theincidence of coronary heart disease in thegeneral population (Figure 21).

Diabetes and Other HighBlood Glucose Conditions:A Major Risk FactorBecause of the soaring prevalence of diabetesworldwide, it now rivals smoking, hypertensionand cholesterol disorders as a major risk factorfor cardiovascular disease. Diabetes alsobelongs to a special risk category as it somarkedly increases the risk of cardiovasculardisease (Figure 22).

Other Cardiovascular Risk Factorsin People with Diabetes

A Higher PrevalenceAll cardiovascular risk factors apply to peoplewith diabetes. Indeed they are even strongerdeterminants in this group (Figures 23 to 26and Table 13). This may be partly explained bythe fact that people with diabetes have a higherprevalence of many cardiovascular risk factors,notably lipid disorders, hypertension, obesityand insulin resistance. These risk factors areinterrelated and are more prominent in type 2diabetes than type 1.

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Figure 21: Estimated coronary heart disease rate according to various combinations of risk factors over 10 yearsAdapted from: Kannel WB (1996)

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Figure 22: Relative risk* of cardiovascular events in people with diabetesAdapted from: Wilson PWF, et al (1992)* The relative risk is the relation between the cardiovascular risk of people with diabetes and thecardiovascular risk of the general population (which equals one). Therefore a relative risk ratio of two forpeople 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 .

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Figure 26: Prevalence of cigarette smoking in people with diabetes

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Figures 23 to 26: Cardiovascular risk factors in people with diabetes in different populationsAdapted from: Keen H, et al (1985)

Figure 23: Prevalence of high cholesterol levels (≥ 4.65 mmol/l) in people with diabetes

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people with diabetes, along with the treatmentof diabetes itself.

But even when other risk factors are taken intoaccount, people with diabetes are still morelikely to die as a resultof cardiovasculardisease. This implies thatsome other factor isresponsible. This factorcould be related todiabetes itself. Since themain characteristic ofdiabetes is high bloodglucose, it is tempting toassume thathyperglycaemia is themain cardiovascular riskfactor in this group. TheUnited KingdomProspective Diabetes Study (UKPDS) hasshown that there is a significant linearcorrelation between haemoglobin A1c(which reflects mean blood glucose levels overthe past three months) and macrovascularevents in type 2 diabetes.

It appears however that any increase in glucoselevels above normal is associated with a higherrisk of coronary heart disease (Figure 27). This

A Stronger ImpactIt has also been demonstrated that mostcardiovascular risk factors have a more harmfulimpact in the presence of diabetes. Forexample, having diabetes lowers by ten yearsthe risk attributed to age in both men andpost-menopausal women. As regards the riskattributed to gender, women with diabetes losethe pre-menopausal protective effect ofoestrogen and therefore have the same age-related risk as men. This implies that thereshould be a higher relative priority given to thepublic health and clinical management ofcardiovascular risk in women with diabetesthan in the general population, where femalesare relatively protected from at least thecoronary heart component of cardiovasculardisease. Also, although prevalence rates aresimilar, the cardiovascular risk attributed tohigh blood cholesterol is doubled in thepresence of diabetes.

The Role of HyperglycaemiaAbout 50% of the excess risk of cardiovasculardisease in type 2 diabetes can be explained bythe higher incidence and/or the strongerimpact of conventional risk factors. Theimplication of this is that the lowering of theseother 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 highblood pressure, but is also seen in the absence of elevatedblood pressure in people with diabetes.

Obesity • Prevalence is stronger in people with diabetes.Weight distribution is also usually different, with morecentral obesity which is linked with a tendency to developcoronary heart disease.

Smoking • People with diabetes smoke less (presumably due tomedical advice).

Table 13: Prevalence of cardiovascular risk factors in people with diabetes compared to people without diabetes

About 50% of theexcess risk ofcardiovasculardisease in type 2diabetes can beexplained by thehigher incidenceand/or higherimpact ofconventional riskfactors.

Fact

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includes impaired fasting glycaemia (IFG) andimpaired glucose tolerance (IGT). It isimportant to note that the risk associated withIGT is approximately double that seen inpeople with normal glucose levels, and alreadyapproaches the level of risk of people withnewly-diagnosed diabetes. As the relationshipbetween glucose levels and risk is continuous,the risk becomes even higher with establisheddiabetes, particularly if it is poorly controlledor of long duration. Although proof of a directcausal relationship is still missing and the exactmechanisms are not fully understood, there isno doubt that raised glucose levels constitute arisk factor for cardiovascular disease in bothpeople with and without diabetes.

Multiple Risk FactorsMany people with diabetes have several riskfactors. As we saw in Figure 21, the presence

of several risk factorshas a multiplicative andnot just an additiveeffect. The situation iseven more serious inpeople with diabetesas, for each risk factorpresent, cardiovascularmortality is about

three times greater than in the generalpopulation (Figure 28).

Type 1 Diabetes

People with type 1 diabetes also have anincreased risk of coronary heart disease,although few studieshave been carried out toattest this. It seemsprudent on the basis ofclinical judgment toconsider that peoplewith type 1 diabetesover the age of 30 yearsare similar to peoplewith type 2 diabetes asregards coronary heartdisease risk. People withtype 1 diabetes who suffer from diabeticnephropathy, regardless of age, should betreated as being at particularly high risk.

New Cardiovascular Risk Factorsand Diabetes

Microalmubinuria, which is a well-knowndisease marker for early diabetic nephropathy,has also been shown to be a risk factor forcardiovascular disease in people with diabetes.The explanation seems to be related to the

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Figure 27: Mean coronary heart disease mortality rates by degree of glucose toleranceAdapted from: Eschwège E, et al (1985)

For each risk factorpresent, the risk ofcardiovascular deathis about three timesgreater in peoplewith diabetes ascompared to peoplewithout thecondition.

Fact

People with type 1diabetes over theage of 30 yearshave a coronaryheart disease risksimilar to peoplewith type 2diabetes.

Fact

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fact that microalbuminuria indicates thepresence of vascular damage.

A number of other new cardiovascular riskfactors have also been identified, although mostof them are still considered as risk markers.The more noteworthy of these arehomocysteine, lipoprotein (a) and C-reactive protein. At the present time there isinsufficient evidence available to justifyincluding them as part of a routine riskassessment.

Conclusion

Due to the higher prevalence and impact ofcardiovascular risk factors, as well as the roleof hyperglycaemia, people with diabeteswithout overt cardiovascular complicationsmerit an intervention against risk factors whichis as aggressive as that which would normallybe provided for individuals with establishedcardiovascular disease.

Figure 28: Impact of multiple risk factors in thepresence of diabetesAdapted from: Stamler J, et al (1993)

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Reducing the Risks

Reducing the RisksC H A P T E R 5

Management of Risk Factorsin the General Population

Many cardiovascular deaths are potentiallypreventable if we can modify known riskfactors. While some risk factors are fixed (suchas age, gender and genetic background), manyothers are modifiable (Table 14). Given thatrisk factors often occur together, all should betreated to gain the most benefit in terms ofreducing cardiovascular disease.

• Diabetes and other high bloodglucose conditions

• Dyslipidaemia• High alcohol consumption• Hypertension• Insulin resistance• Obesity• Sedentary lifestyle• Smoking

Table 14: Modifiable cardiovascular risk factors inthe general population

Modifiable cardiovascular risk factors in thegeneral population are listed in alphabeticalorder below:

Diabetes and other high blood glucose conditions:Although, as stated in Chapter 4, high glucoselevels constitute a cardiovascular risk factor inpeople with and without diabetes, there is atpresent no evidence that the treatment ofminor increases in blood glucose (which fallshort of overt diabetes) decreases thesubsequent development of cardiovasculardisease. At the very least however, the findingof any rise in glucose levels should promote acareful search for and treatment of othercardiovascular risk factors.

Dyslipidaemia (see page 45): There is strongevidence that reducing elevated levels of LDLcholesterol diminishes the risk of coronaryheart disease. High levels of HDL cholesterolare also known to decrease the risk ofcoronary heart disease. Therefore raising HDLcholesterol in people with low HDLcholesterol levels may provide benefit. It is alsolikely that lowering high triglycerides has asimilar effect. Reducing lipid levels may also bebeneficial in the prevention of stroke andperipheral vascular disease.

The first line of treatment is lifestylemodification by improving diet, taking morephysical exercise and losing excess body weight.If these measures fail then drug treatment canalso be prescribed. A group of drugs calledstatins are particularly useful for lowering LDLcholesterol. Another group known as fibratescan be used to target triglycerides.Combinations of these can be used if required.

Hypertension (see page 46): The lowering ofelevated blood pressure substantially cuts therisk of stroke and coronary heart disease. Iflifestyle measures including salt restriction areinsufficient then antihypertensive drugs (egangiotensin converting enzyme (ACE)inhibitors, beta blockers, calcium channelblockers, diuretics) should also beadministered. It is worth noting that manypeople will require more than one drug.

Insulin resistance (see page 46): Insulinresistance is usually either caused oraggravated by obesity, particularly abdominalobesity. Hence diet to promote the loss ofexcess weight, together with exercise toimprove muscle metabolism and aid weight losscan improve insulin sensitivity. When diabetes ispresent, tight glucose control can also enhance

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insulin sensitivity. Drugs which specificallytarget insulin resistance are now becomingavailable, but it is not yet known whetherdecreasing insulin resistance will in itself slowor prevent the development of cardiovasculardisease.

Obesity (see page 46): Sustained weight loss inthe overweight is of benefit for allcardiovascular diseases. It is also instrumentalin decreasing other risk factors such as raisedblood pressure and high lipids.

Risk factor Treatment Results of treatment

Diabetes and other • Lifestyle modifications Although it prevents coronaryhigh blood glucose • Drugs: oral hypoglycaemic heart disease, at present the effectconditions agents, insulin. of blood glucose lowering alone

may not be as strong as themodification of other majorrisk factors.

Dyslipidaemia • Lifestyle modifications: eg diet, Decreases the risk of coronaryphysical exercise and lowering heart disease. May also be beneficialexcess 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 andconsumption drink in moderation. coronary heart disease.

Hypertension • Lifestyle modifications: Reduces the risk of stroke andeg salt restriction. coronary heart disease.

• Drugs: beta blockers, calciumchannel blockers, ACE inhibitors,diuretics, etc.

Insulin resistance • Lifestyle modifications: It is not yet known whetherdiet, exercise. decreasing insulin resistance will

• Tight glucose control in in itself slow or prevent thediabetes. development of cardiovascular

disease.

Obesity • Lifestyle modifications: Prevents all cardiovascularachieving normal body weight, diseases. Decreases other riskincreasing physical activity. factors such as blood pressure,

high glucose and high lipids.

Sedentary lifestyle • Lifestyle modifications: Reduces body fat, raises HDLincreasing in particular cholesterol levels, lowers LDLaerobic physical activity. cholesterol and triglyceride levels,

increases insulin sensitivity, andlowers blood glucose and bloodpressure.

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

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Sedentary lifestyle (see page 46): There iscompelling evidence that aerobic physicalactivity reduces the risk of coronary heartdisease. People who exercise regularly have lessbody fat, higher HDL cholesterol levels, lowerLDL cholesterol and triglyceride levels, greaterinsulin sensitivity, lower blood glucose andblood pressure, and usually have an improvedsense of well-being.

Smoking (see page 46): Stopping smoking is ofmajor benefit in the prevention of coronaryheart disease, stroke and peripheral vasculardisease, even in those who have smoked for avery long time.

Some risk factors cannot be easily measuredand others may remain to be identified. For thisreason, certain interventions may be found tobe very effective even though they do nottarget a specific measured risk factor. A goodexample of this is aspirin, which has proved ofmajor benefit in preventing coronary heartdisease.

Management of Risk Factorsin People with CardiovascularDisease

Even greater attention should be paid to riskfactors in people who have already developedcardiovascular disease. For instance smokingmust be avoided, and all people with coronaryheart disease should be taking aspirin (unless aspecific contraindication to its use is present).Meticulous attention to blood pressure andlipid control is also vital.

Management of Risk Factorsin People with Diabetes

As many people with diabetes who experiencea first coronary event die prior to getting tohospital, they cannot benefit from secondaryprevention strategies. In view of this, as well asthe increased overall risk associated withdiabetes, the management of risk factors inpeople with diabetes should precede the onsetof heart or other vascular disease and should

be pursued as aggressively as it would be inindividuals with established vascular disease.

As is the case for the general population, thefirst line of action in managing risk factors inpeople with diabetes should be lifestylemodifications. If this is not sufficient then drugscan also be prescribed. The lifestyle and drugmeasures summarized in Table 15 also apply topeople with diabetes. In addition, screening formicroalbuminuria (see page 50) is important,and specific interventions can help delay itsprogression.

Although people with diabetes and theirphysicians may be reluctant to add anotherdrug to an already overwhelming regimen ofmedication, a number of recent studies haveshown the extent to which some risk factorscan be modified by medication in people withthe condition. The results of these studies aresummarized below and in Table 16.

Dyslipidaemia

A subgroup analysis of the ScandinavianSimvastatin Survival Study (4S) showed thebenefits of decreasing LDL cholesterol levelswith a statin in people with diabetes andcoronary heart disease. This produced an evengreater reduction in the rate of coronaryevents than in people without diabetes (55%versus 32%). In the diabetes group there was asaving of one life for every four patientstreated, as opposed to one in 13 in the groupof people without the condition.

In the Cholesterol and Recurrent Events Trial(CARE) the people studied also had coronaryheart disease, but had lower cholesterol levels.Statin therapy in this study cut the risk ofcoronary events by a similar degree in peoplewith and without diabetes.

The aim of the Veterans Affairs HDL InterventionTrial (VA-HIT) was to use fibrate therapy toraise HDL cholesterol and lower triglyceridesin men with documented coronary heartdisease and low HDL cholesterol. In thediabetic group there was a 22% relative riskreduction of a first non-fatal heart attack or

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coronary heart disease death, and a significantdecline in cerebrovascular events.

It is thus clear that lipid lowering with eitherstatins or fibrates is beneficial in people withtype 2 diabetes, particularly if they already havecoronary heart disease. Although there isevidence to suggest the same benefit forpeople with diabetes but without coronaryheart disease, this remains to be confirmed.

Hypertension

In the part of the UKPDS that dealt withhypertension, people with type 2 diabetes wererandomized to intensive or conventionaltreatment using either a beta blocker or anACE inhibitor. The average blood pressure wasimproved by 10 mm Hg systolic and 5 mm Hgdiastolic. This resulted in a reduction of therisks for heart failure (56%), stroke (44%) anddeaths related to diabetes (32%). Currentpractice is to aim for normal blood pressurevalues, particularly in those with other riskfactors and those who have alreadyexperienced a cardiovascular event.

Strategy Complication Reduction of complication

Lipid control • Coronary heart disease mortality Ô 36%1

• Major coronary heart disease event Ô 55%1

• Any atherosclerotic event Ô 37%1

• Cerebrovascular disease event Ô 62%1

Blood pressure control • Cardiovascular disease Ô 51%2

• Heart failure Ô 56%3

• Stroke Ô 44%3

• Diabetes-related deaths Ô 32%3

Blood glucose control • Heart attack Ô 37%3

1 The 4S Study2 Hypertension Optimal Treatment (HOT) Randomised Trial3 UKPDS

Table 16: Highest percentage reduction of the risk of diabetic complications in people with type 2 diabetesshown in recent studiesAdapted from: International Diabetes Federation (1999)

Hyperglycaemia

Data from the UKPDS suggest that there isbenefit in tightly controlling blood glucose inpeople with diabetes. This was particularlyevident in a group of overweight subjects whowere treated with an oral hypoglycaemic agent(metformin), in whoma 37% reduction in heartattacks was recorded,and also when bloodglucose lowering andblood pressure controlwere combined. Thelatter finding emphasizesthe importance oftreatment strategiesaimed at multiple riskfactors.

It is worth noting that,over time, a combinationof different oral agentsand insulin is requiredfor blood glucosecontrol in type 2 diabetes. In type 1 diabetesthere was also a hint in the DCCT that tightcontrol of blood glucose improvescardiovascular outcomes.

Whilecardiovasculardeaths havedeclined in thosewithout diabetes indeveloped countries,in men withdiabetes thedecrease has beenmodest, while inwomen withdiabetes the rateshave actuallyincreased.

Fact

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Putting the Theory into Practice

These positive results call for aggressive actionto be taken to treat the cardiovascular riskfactors that are common in people withdiabetes.

Despite these findings, a recent US studyrevealed that while cardiovascular diseasemortality and particularly coronary heartdisease related deaths have declined in thosewithout diabetes, in men with diabetes thedecrease has been a modest 13%, while inwomen with diabetes the rates have actuallyincreased by 23% (Figure 29).

This suggests that approaches proven toreduce cardiovascular disease in people withdiabetes are frequently not implemented inclinical practice. There is therefore a clear needfor improved awareness of treatmentpossibilities among healthcare professionals.

Guidelines with specific targets forcardiovascular risk factors in people with type 1and type 2 diabetes have been published by theEuropean and Western Pacific Regions of IDF.Many other national and regional guidelines also

exist. However it should be noted that therelationship between risk factors and disease isgenerally continuous and additional benefits maybe obtained by lowering risk factors even further.

Risk factors Targets

Dyslipidaemia • Decrease LDL cholesterollevels(<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 riskfactors in people with diabetes*These levels are based on IDF Europe’s guidelines.Other guidelines, for example those from the USAor Latin America, may give slightly different targetvalues.

Other Risk Factors

In people with diabetes other factors are alsoassociated with cardiovascular disease, such asincreased ‘stickiness’ of the blood andhardening of arteries. It is not known at thisstage whether treatment of such factors isbeneficial.

National Approachesto Prevention: Lifestyle

Preventing Diabetes andCardiovascular Disease

The global changes in lifestyle – such as ahigher intake of fat, salt and calories, as well asdecreased physical activity – have led to anupsurge in cardiovascular disease and type 2diabetes. In many countries specificmanifestations of lifestyle changes include anincrease in the amount of junk food consumedand the replacement of physical activity by

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television, video games and internet browsing.Increasing urbanization and mechanization arealso responsible for the general decline inphysical activity levels.

It is obvious that lifestyle modification can beof major benefit in preventing non-communicable diseases such as cardiovasculardisease and diabetes. Although they may bechallenging for the individual to implement,lifestyle changes are cheap, effective and free ofside effects.

On the national level, a broad population-basedapproach to prevention is probably more cost-effective than merely targeting high-riskindividuals, although both methods can beeffectively combined. Ideally a population-basedapproach should begin in childhood whenhealth-risk behaviour begins. Parents, teachersand peer groups should be involved inimparting health education to children, as asharp rise in the prevalence of childhoodobesity and young-onset type 2 diabetes hasbeen recently reported from several countries.

Healthy eating habits should be encouraged,emphasizing a reduction in total calories, fatand sugar, and an increase in the intake of fibre,fruit and vegetables. The ‘healthy option’ shouldbe made more accessible and affordable for all.In the UK for example free fruit is now beinggiven to school children and wide publicity isbeing given to the message that everybodyshould eat five portions of fruit and vegetablesa day.

Regular physical exercise, eg aerobic exerciseslike walking, jogging, swimming or cycling, canhelp to prevent diabetes and reducecardiovascular disease risk factors. Relaxationtechniques can also play a role in theprevention of cardiovascular disease. Exercisecan be promoted by initiatives such asproviding public sports facilities in thecommunity.

Cigarette smoking rates have already startedfalling in the Western world but unfortunatelythey are on the increase in developingcountries. Some of the successful measures to

curb smoking include raising government taxes,restricting smoking in the workplace and publicplaces, and banning advertising and sponsorshipby tobacco companies.

The implementation of national programmeswhich focus upon primary prevention isessential. Economies of scale can potentially beachieved by linking or integrating programmes.Examples include programmes relating toenvironmental pollution, public transportservices, urban planning and architecture. TheWHO concept of the ‘Healthy City’ applieswith great force to primary preventionprogrammes.

Factors which hamper success include thehostile modern environment (particularly inurbanized settings), the impact of consumerism,the interest of multinational companies andsocio-economic pressures.

✓ A healthy, balanced diet (less fat, salt, refinedsugar, alcohol and calories; more fibre, fruitand vegetables)

✓ Regular physical activity (eg aerobicexercises)

✓ A healthy social life and relaxationtechniques to combat stress

✓ Smoking cessation✓ Sustained weight loss in the overweight

Table 18: Lifestyle behaviour to be promoted

Preventing Cardiovascular Diseasein People with Diabetes

Cardiovascular disease prevention in peoplewith diabetes should in the first place be partof a comprehensive approach to prevention inthe whole community. It is inevitably easier forpeople with diabetes to change lifestylebehaviour if this is occurring in the populationat large. There should be national guidelines onlifestyle modification leading to an overallhealthier population, with particular emphasison people with diabetes. These kinds ofactivities tend to be more successful whenbased on local initiatives (ie the bottom-upapproach). Such initiatives are being promotedby IDF and WHO.

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Treatment

Treatment of CardiovascularDisease in Diabetes

C H A P T E R 6

This chapter deals in general terms with themain issues relating to the treatment ofcardiovascular disease in diabetes. Specificdetails with regard to the exact implementationand choice of treatment regimes is beyond thescope of this publication.

Many of the treatment modalities forcardiovascular disease are similar irrespective ofwhether diabetes is present or not. Howeverspecific issues related to diabetes include thedifficulty of diagnosing silent cardiovasculardisease, the need for the aggressive managementof all risk factors, and the use of insulin therapyto achieve blood glucose control when a heartattack occurs.

Treatment of CoronaryHeart Disease

Assessment

An electrocardiogram (ECG) may behelpful for screening people at risk, particularlyCaucasians and south Asians over the age of 40.The first step is to screen patients with anginaor any other coronary heart disease symptoms.However, in view of the often silent,asymptomatic nature of coronary heart diseasein people with type 2 diabetes, the diagnosisoften needs to be made by exercise cardiacstress testing. If the symptoms and/or thetest findings are highly suggestive of coronaryheart disease, the person will require furtherinvestigation. In these patients allcardiovascular risk factors must be re-examined and treated aggressively.

Treatment

People with stable angina are usually treatedby tight control of cardiovascular risk factors

and by prescribing drugs (eg aspirin, beta-blockers, nitrates and long-acting calciumchannel blockers). When unstable anginadevelops, the risk of heart attack is very highand rapid preventive treatment in an intensiveor coronary care unit may be required.

People with diabetes who have experienced anacute heart attack benefit to the same degree,and in some cases even more, from therapeuticinterventions that are used in people withoutdiabetes (Table 19).

Treatment Effectiveness in peoplewith diabetes

Aspirin • Equally effective

Beta-blockers • Equally effective

ACE inhibitors • Particularly advantageousif started within 24 hours

Statins • Equally effective

Clot dissolving • Useful within the firstagents (thrombo- 12 hours, although slightlylytic therapy) less effective in diabetes

Table 19: Treatments for patients who haveexperienced an acute heart attack and theireffectiveness in people with diabetes compared tothe general population

Intensive insulin therapy for tight blood glucosecontrol when the patient is in hospital has alsoproven to decrease death rates, and may bebeneficial for at least three months followinghospitalization. The DIGAMI Study from Swedenstresses the importance of controlling bloodglucose levels during the acute phase anddemonstrates that intensive insulin treatmentalso improves survival over the longer term,

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with a 24% reduction in death rates after threeand a half years. This means a saving of one lifefor every nine patients on intensive insulin

treatment.

If people withdiabetes requirerevascularization –a procedure to eitheropen up blocked bloodvessels (angioplasty)or to bypass themusing implanted vesselsfrom other parts of thebody (bypasssurgery) - bypass hasproven to be ajudicious choice,

particularly when several coronary vessels areinvolved, which is frequently the case indiabetes. The use of tiny metal devices calledstents to keep arteries open has also improvedthe prognosis of some patients with diabetesand coronary heart disease.

Heart failure is a complication of coronaryheart disease which occurs more frequently inpeople with diabetes. It is usually treated withdrugs such as ‘water tablets’ (diuretics), ACEinhibitors, beta-blockers and digitalis.

Treatment of CerebrovascularDisease

As well as being a risk factor for stroke,diabetes and other high blood glucoseconditions have adverse effects on both theshort and long-term prognosis for strokevictims. Hyperglycaemia in the acute phase ofstroke has been associated with high deathrates, regardless of the presence or absence ofdiabetes. Tight glucose control improves thetime of recovery.

The standard therapies of intervention instroke in people without diabetes are alsohelpful in people with diabetes. Indeed, theeffect of aspirin on cardiovascular eventsincluding stroke in people with diabetes has

been suggested to be even stronger than inpeople without diabetes.

Resources need to be made available for therehabilitation of stroke patients, which may beparticularly complicated in people withdiabetes due to the presence of othercomplications.

Treatment of PeripheralVascular Disease

Almost all people with diabetes who haveestablished vascular disease (including diabeticfoot problems, microvascular disease,macrovascular disease, neuropathy and a historyof amputations) present a higher risk ofamputation in another limb as well as a greaterrisk of heart attack and cardiovascular death.

In people with both diabetes and peripheralvascular disease, revascularization performed byan expert team can be a good alternative toamputation. The use of pharmacologicalinterventions depends on the nature of theunderlying disease. However the benefit ofdrugs is unproven.

The best treatment of the diabetic foot isprevention. This can only be achieved byeducating people with diabetes about foot care.Although not all foot complications can beprevented, dramatic reductions in theirfrequency can be achieved through theimplementation of diabetic foot programmes bya multidisciplinary team involving primaryhealthcare professionals, community carers andthe diabetes team. There should also be betteraccess to amputation, rehabilitation, prosthesesand chiropody facilities for all patients.

ConclusionSince there are many risk factors involved, thetreatment and follow-up of cardiovasculardisease in people with diabetes can be acomplicated, time-consuming and expensiveprocess. Therefore the value of the preventivemeasures outlined in Chapter 5 cannot beoveremphasized.

Intensive insulintreatment in thosewho haveexperienced anacute heart attackimproves survivalover the short andlong term with a24% reduction indeaths after threeand a half years.

Fact

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ConclusionThe contents of this publication can leave thereader in no doubt as to the magnitude of theproblems posed by diabetes and itscardiovascular complications, which are a major

cause of illness, deathand healthcare costs. Itis also manifest thatthese problems areglobal in perspectiveand are rapidlyworsening.

The good news is thatit is possible to takeaction to slow or stopthe consequences of

cardiovascular disease in diabetes. But therecan be no doubt that now is the time to act.

Action must be taken on four levels:1. Prevention2. Treatment3. Education/Awareness4. Research

Prevention

Investment in primary and secondaryprevention strategies is potentially the mosteffective measure in the long term, in bothhuman and economic terms.

It is necessary to adopt an uncompromisingmultifactorial approach to prevent or slow theprogression of cardiovascular disease in peoplewith diabetes. Fundamental aspects ofprevention include:

• Promoting a healthy lifestyle. Primaryprevention of diabetes by lifestylemodification has the advantage that it will

simultaneously help to reduce othercardiovascular risk factors such ashypertension, obesity and dyslipidaemia. Thelifestyle changes required can besummarized very simply by the IDF slogan‘Eat Less, Walk More’.

• Early screening for diabetes and itscomplications. This will enable interventionin the early stages of cardiovascularcomplications. However it must berecognized that this may lead to a short-term rise in the use of resources as a resultof an increased identification of new cases.This should be viewed as an advantagerather than a disadvantage, since earlydetection has obvious long-term benefits.

• Investment in national programmes aimed atprimary and secondary prevention ofdiabetes and its cardiovascularcomplications. These programmes can beintegrated or linked with other health orenvironmental programmes.

Treatment

Adequate healthcare resources need to bemade available not only for prevention, but alsofor the treatment of established diabetes andits cardiovascular complications. This means theprovision of essential medical treatment, sothat the best possible prognosis can beensured. At the very least we should aim for asimilar decline in cardiovascular diseasemortality for people with diabetes around theworld as that which has been witnessed inpeople without diabetes in many developedcountries in recent years.

The Way ForwardC O N C L U S I O N

It is possible to takeaction to slow orstop theconsequences ofcardiovasculardisease in diabetes.Now is the time toact.

Fact

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Education/Awareness

Education and awareness at all levels and strataof society is the key to success.• Governments: Decision makers need to be

made aware of the close link betweendiabetes and cardiovascular disease and that,if measures are not taken to preventdiabetes in the first place, a global explosionof cardiovascular disease is waiting tohappen. Given that there is a lot of overlapin the prevention techniques for the twodiseases, investment in prevention can yielda high return.

• Healthcare professionals: As reported in thisbook, the cardiovascular risk factors indiabetes have been identified by many recentstudies. A number of these risk factors aremodifiable and it has been proven possibleto reduce their impact dramatically.Healthcare professionals must be madeaware of the importance of systematicallyand aggressively implementing these findingsin clinical practice.

• Public: People with diabetes in particularneed to be aware of the commoncardiovascular risk factors and the lifestyleand other measures that can be taken todecrease or delay their chance of developingcardiovascular disease.

Research

Expanded basic and clinical research is neededin order to gain a better understanding of thefactors that contribute to the excess risk ofpremature cardiovascular disease in peoplewith diabetes. In the future new therapiesshould aim to decrease the cardiovascular riskof people with diabetes to the same level asthat of people without diabetes.

Conclusion

It is hoped that Diabetes and CardiovascularDisease: Time to Act will prompt action on all theseplanes. Success can only be achieved throughteamwork and collaboration. IDF and its member

associations must work together with other non-governmental organizations and WHO to put ahalt to the double scourge of diabetes andcardiovascular disease, and to make governmentsaware that action must be taken urgently.

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The good news is that it is possible to take action to slow or stop the consequencesof cardiovascular disease in diabetes. Now is the time to act.

Ten facts and figures about diabetes and cardiovascular disease:

1. It is estimated that there are at least 150 million people in the world withdiabetes now. This figure is expected to double over the next 25 years.

2. Cardiovascular disease is the number one cause of death in industrializedcountries. It is also set to overtake infectious diseases as the most common causeof death in many parts of the less developed world.

3. People with diabetes are two to four times more likely to develop cardiovasculardisease than people without diabetes, making it the most common complication ofdiabetes.

4. People with type 2 diabetes have the same risk of heart attack as people withoutdiabetes who have already had a heart attack.

5. People with diabetes can have a heart attack without even realizing it.

6. Strokes occur twice as often in people with diabetes and high blood pressure as inthose with high blood pressure alone.

7. Transient ischaemic attacks (mini-strokes) occur between two and six times morefrequently in people with diabetes.

8. People with diabetes are 15 to 40 times more likely to require a lower-limbamputation compared to the general population.

9. For each risk factor present, the risk of cardiovascular death is about three timesgreater in people with diabetes as compared to people without the condition.

10. While cardiovascular disease mortality and in particular coronary heart diseaserelated deaths have declined in those without diabetes in developed countries, inmen with diabetes the decrease has been a modest 13%, while in women withdiabetes the rates have actually increased by 23%.

Fact File

The good news is that it is possible to take action to slow or stop the consequencesof cardiovascular disease in diabetes. Now is the time to act.

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Diagnostic Criteria

Diagnostic Criteria for Diabetesand its Risk States

A N N E X 1

In the majority of affected individuals thediagnosis of diabetes is straightforward.However it may cause problems for those withminor degrees of hyperglycaemia. If someonehas typical symptoms of diabetes and a clearlyraised plasma glucose level, the diagnosis isclear. A person with ketones in the urine andhigh glucose does not present a problem either.However in the person without symptoms, twoabnormal results on separate occasions areneeded.

Diagnostic values are shown in Table 20. Thecut-off points are based on the risk ofsubsequently developing the specificcomplications of diabetes: retinopathy,nephropathy and neuropathy. To distinguishbetween different types of diabetes, furthertests may be needed, but this is usually notrequired in the clinical setting.

Venousplasma*glucoseconcentration,mmol l-1 (mg dl–1)

Diabetes mellitus

Fasting ≥ 7.0 (≥ 126)or

2–h post glucose load ≥ 11.1 (≥ 200)

Impaired glucose tolerance (IGT)

Fasting (if measured) < 7.0 (< 126)and

2–h post glucose load ≥ 7.8 (≥ 140)

Impaired fasting glycaemia (IFG)

Fasting ≥ 6.1 (≥ 110) and< 7.0 (< 126)

and (if measured)2-h post glucose load < 7.8 (< 140)

Table 20: Diagnostic values for diabetes and itsrisk states*Please note that these values refer to venousplasma glucose. Values for whole venous blood andcapillary blood are slightly different. For moreinformation on this and the diagnosis andclassification of diabetes in general, see AlbertiKGMM (1999).

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Diabetes Prevalence

Diabetes PrevalenceA N N E X 2

Prevalence (20-79 age group)

0% 2% 4% 6% 8% 10% 12% 14% 16%

Albania✗ (all age groups)Dominican Republic

CroatiaPortugal

MacedoniaFinland✗ (45-64 age group)

PolandIndia

GreeceAustralia

Korea, Republic of Spain✗ (10-74 age group)

Denmark✗ (60-74 age group)Jordan

Malaysia✗ (35 age group)Sweden✗ (all age groups)

HungaryLebanon

KuwaitItaly

SyriaIsrael

Georgia, Republic of✗ (all age groups)Japan

Qatar

New Zealand

USA (20 age group)

Jamaica

Slovenia✗ (all age groups)

Bahamas

CubaSlovakia✗ (all age groups)

Puerto Rico

FijiTaiwan✗

Egypt✗ (20 age group)Saudi Arabia

Malta (35-69 age group)Netherlands Antilles

Macao SAR, PRCSingapore, Republic of

Tonga✗

Czech Republic✗ (all age groups)Pakistan

Hong Kong SAR, PRCSt Kitts and Nevis✗

Grenada✗

Cayman Islands✗

British Virgin Islands✗

Bermuda✗

Aruba✗

BarbadosTrinidad and Tobago (35-69 age group)

Mexico (35-64 age group)Bahrain

MauritiusDominica, Commonwealth of✗ (65 age group)

Papua New Guinea

Estimated diabetes prevalence

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Prevalence (20-79 age group)

0% 2% 4% 6% 8% 10% 12% 14% 16%

Romania✗ (all age groups)Gambia

GhanaMali

Nigeria

TogoCôte d’Ivoire

Congo, Republic of Senegal

GabonCameroon

Tanzania

Ethiopia

ZimbabweMadagascar

UgandaZambia

Congo, Dem Republic of Mozambique

Chile (over 20 age group)Kazakhstan Republic✗ (all age groups)

Kenya

IcelandBangladesh✗ (15 age group)

MoroccoLibya

China, People’s Republic of Sri Lanka

PanamaGuatemala

EcuadorPhilippines

GuyanaTunisia

BrazilIreland, Republic of

Lithuania✗ (all age groups)

Argentina

Costa RicaBelize

Sudan✗ (25 age group)

United KingdomUkraine✗ (all age groups)

NetherlandsThailand

PeruSwitzerland

Kyrgyz RepublicNorway

Luxembourg

AustriaIran

ColombiaBolivia

FranceSouth Africa

Venezuela

Honduras

BelgiumBulgaria✗ (all age groups)

Iraq

SurinameGermanyUruguay

ParaguayTurkey

EstoniaIndonesia (15-74 age group)

El SalvadorHaiti

CyprusCanada (18-74 age group)

Estimated diabetes prevalence (continued)

✗ = crude valueSource: International Diabetes Federation (2000)

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Mortality Rates

Coronary Heart Disease andCerebrovascular DiseaseMortality Rates

A N N E X 3

AustraliaGreece

Puerto RicoGuam*

SloveniaColombia

IsraelNetherlands

GuyanaMongolia*

UruguayCanadaBahrain

BahamasMacedonia

GermanySweden

SurinameAustria

CubaVenezuela

United States of AmericaMalta

CroatiaSingapore, Republic of

NorwayPoland

Tajikistan*United Kingdom

New ZealandFinland

Yugoslavia*Romania

KuwaitIreland, Republic of

MauritiusTrinidad and TobagoGeorgia, Republic of

Kyrgyz RepublicCzech Republic

HungaryArmenia*

Uzbekistan*

UkraineLithuania

Moldova, Republic of*Belarus*Estonia

Kazakhstan RepublicAzerbaijan Republic

Turkmenistan*RussiaLatvia*

Fiji

BulgariaAmerican Samoa*

Palau*

Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Coronary heart disease in males

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TurkeyZimbabwe

São Tomé and Príncipe*Peru

EcuadorKorea, Republic of

GuatemalaJapan

TaiwanDominican Republic

NicaraguaEgypt

El SalvadorChina, Peoples' Republic of

Hong Kong SAR, PRCSouth Africa

FranceJamaica

SpainSri Lanka

PanamaAntigua and Barbuda*

Dominica, Commonwealth ofBarbados

Northern Mariana Islands*

Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Coronary heart disease in males (continued)

Albania

PortugalSeychelles*

ChileParaguay

PhilippinesMexico

St Lucia*Belize

BelgiumArgentina

ItalyCosta Rica

LuxembourgCook Islands*

Brazil

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ParaguayCanada

BarbadosSwedenUruguayMexico

Puerto RicoGuam*

Germany

AustraliaAustria

NorwayPoland

IsraelBahamas

Costa RicaFinland

MacedoniaCroatia

United States of AmericaMongolia*ColombiaSuriname

United KingdomBelize

VenezuelaKuwait

MaltaSingapore, Republic of

New ZealandBulgariaBahrain

Ireland, Republic ofYugoslavia*

CubaRomania

Czech RepublicHungary

Tajikistan*

MauritiusLithuania

Georgia, Republic ofKyrgyz Republic

EstoniaArmenia*

UkraineTrinidad and Tobago

Latvia*Belarus*

RussiaKazakhstan RepublicAzerbaijan Republic

Uzbekistan*Turkmenistan*

Moldova, Republic of*

Fiji

Cook Islands*

Brazil

Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Coronary heart disease in females

BelgiumLuxembourg

GuyanaGreece

ChileChina, Peoples' Republic of

Antigua and Barbuda*Jamaica

Seychelles*PanamaSlovenia

PhilippinesNetherlands

St Lucia*

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Northern Mariana Islands*

PeruKorea, Republic of

JapanEcuador

FranceEgypt

Sri LankaDominica, Commonwealth of

TaiwanGuatemala

São Tomé and Príncipe*Spain

Dominican RepublicAlbania

Hong Kong SAR, PRC

ArgentinaItaly

NicaraguaEl Salvador

South AfricaPortugal

American Samoa*

Palau*

ZimbabweTurkey

Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Coronary heart disease in females (continued)

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Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

ColombiaCuba

South AfricaSuriname

Martinique*Venezuela

Chile

Singapore, Republic ofUruguay

PolandDominica, Commonwealth of

AlbaniaPhilippines

SloveniaBelize

Paraguay

BarbadosArgentina

TaiwanArmenia*Bahamas

Tajikistan*Portugal

Lithuania

Mongolia*Czech Republic

Seychelles*Azerbaijan Republic

Tanzania

Antigua and Barbuda*JamaicaCroatia

St Lucia*Trinidad and Tobago

Korea, Republic ofMacedonia

Uzbekistan*Hungary

Georgia, Republic ofTurkmenistan*

China, Peoples' Republic ofBelarus*

EstoniaMauritius

Yugoslavia*Kazakhstan Republic

RomaniaMoldova, Republic of*

BulgariaLatvia*

GuyanaRussia

Kyrgyz RepublicUkraine

Cook Islands*

Northern Mariana Islands*

American Samoa*

Brazil

Fiji

Cerebrovascular disease in males

São Tomé and Príncipe*

IsraelEl Salvador

United KingdomItaly

New ZealandNicaraguaGermany

MaltaIreland, Republic of

AustriaHong Kong SAR, PRC

JapanPanamaFinlandGreece

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Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

PeruGuatemalaBotswana*

CanadaAustralia

KuwaitBahrainTurkeyFrance

United States of AmericaPuerto Rico

Sri LankaDominican Republic

NetherlandsSweden

EgyptBelgium

LuxembourgCosta Rica

NorwayEcuadorGuam*

SpainMexico

Zimbabwe

Palau*

Cerebrovascular disease in males (continued)

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NicaraguaBarbados

GreeceChile

PhilippinesAntigua and Barbuda*

Poland

SloveniaArgentina

AlbaniaSão Tomé and Príncipe*

Uruguay

VenezuelaColombiaBahamas

CubaTaiwan

SurinameSouth Africa

PortugalSingapore, Republic of

Seychelles*Czech Republic

ParaguayBelize

LithuaniaMongolia*

HungaryKorea, Republic of

CroatiaTajikistan*

Trinidad and TobagoArmenia*

Azerbaijan RepublicDominica, Commonwealth of

MauritiusTanzaniaEstonia

China, Peoples' Republic ofUzbekistan*

Georgia, Republic ofMacedonia

JamaicaBelarus*Bulgaria

Turkmenistan*Latvia*

GuyanaSt Lucia*Romania

Kazakhstan RepublicYugoslavia*

RussiaMoldova, Republic of*

Kyrgyz Republic

UkraineAmerican Samoa*

Brazil

Fiji

Northern Mariana Islands*

Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Cerebrovascular disease in females

Dominican RepublicEcuador

JapanGuam*

United KingdomEl Salvador

Hong Kong SAR, PRCFinlandPanama

MaltaNew Zealand

Martinique*Luxembourg

MexicoIreland, Republic of

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For information on sources and methodology, see page 25

Cook Islands*

PeruKuwaitFrance

Puerto RicoCanada

Sri LankaAustraliaSweden

GuatemalaUnited States of America

SpainTurkey

NetherlandsBelgium

EgyptNorway

ItalyIsrael

ZimbabweGermany

AustriaCosta Rica

Palau*

BahrainBotswana*

Mortality (per 100,000 population per year)

0 100 200 300 400 500 600 700 800

Cerebrovascular disease in females (continued)

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Studies

Studies of Diabetes andHeart Disease

A N N E X 4

� Cholesterol and RecurrentEvents Trial (CARE)

The objective of the CARE study was to assessthe effect of a statin on the risk of fatal or non-fatal heart attacks in people with coronaryheart disease and high cholesterol levels. 14%of the participants had diabetes.

The study demonstrated a 25% reduction ofmajor coronary events in people with diabeteson statin therapy. Total cholesterol levels werecut by 19%, LDL cholesterol by 27%, andtriglycerides by 13%. HDL cholesterol wasincreased by 4%.

� Diabetes Control andComplications Trial (DCCT)

The DCCT was a clinical study conducted from1983 to 1993 by the US National Institute ofDiabetes and Digestive and Kidney Diseases(NIDDK). The DCCT involved 1440volunteers who had type 1 diabetes for at leastone year but no longer than 15 years. They alsowere required to have no, or only early signs of,diabetic eye disease.

The study compared the effects of twotreatment regimens - standard therapy andintensive control - on the complications ofdiabetes. Volunteers were randomly assignedto each treatment group. The study showedthat keeping blood glucose levels as close tonormal as possible slowed the onset andprogression of diabetic eye, kidney and nervediseases.

� Diabetes Mellitus, InsulinGlucose Infusion in AcuteMyocardial Infarction Study(DIGAMI)

The objective of the DIGAMI study was todetermine the long-term effect of intensiveinsulin treatment initiated at the time of anacute heart attack on 620 people with diabetes.

Patients were randomly assigned to eitherintensive insulin treatment or standardtreatment. During an average follow-up of overthree years a significant mortality riskreduction (24%) was recorded in theintensively treated group.

� Hypertension OptimalTreatment Randomized Trial(HOT)

The HOT study is the largest trial everconducted of the results of treatinghypertension. Almost 18,800 patients from 26countries were followed up for an average ofjust under four years. 8% of the patients haddiabetes. HOT’s objective was to find out howfar blood pressure should be lowered usingantihypertensive drugs in order to achieve themaximum decreases in strokes and heartattacks in people with hypertension.

Compared to the people with diabetes in thegroup with diastolic blood pressure kept at 90or below, those in the group 80 or below had a51% reduction in major cardiovascular eventsand a 30% reduction in strokes.

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� MONICA Project

The WHO MONICA Project is the largestcommunity-based study on heart disease everundertaken. The results show that heartdisease rates are related to changes in majorcoronary risk factors and to the introductionof new medical treatments.

The MONICA Project studied more than 30populations (mainly from Europe) from themid-1980s to the mid-1990s. More than sevenmillion men and women aged between 35 and64 years of age were monitored to examine ifand how certain coronary risk factors and newtreatments for heart disease contribute to therise or fall of heart disease rates in thesecommunities.

Risk factors such as cigarette smoking, bloodpressure, blood cholesterol and body weightwere studied. Treatments taken intoconsideration included aspirin, beta blockers,ACE inhibitors, clot dissolving agents andcoronary artery surgery.

Heart disease rates fell in most of thepopulations studied, as did cigarette smoking inmen, blood pressure and blood cholesterol.Smoking in women showed a mixed picture andweight rose in both men and women in mostpopulations.

Taking all populations as a whole, the decline insmoking seems to have contributed most tothe reduction in the risk of heart disease inmen. In women, the decrease in blood pressureemerged as the strongest determinant. Overall,it was found that the relation between the fallin heart disease rates and the change in riskfactors was more apparent in men than inwomen.

� Scandinavian SimvastatinSurvival Study (4S)

The objective of the diabetes sub-study of the4S was to assess the effect of a statin onmortality and the risk of a major coronaryevent in people with coronary heart diseaseand high cholesterol levels. 5% of the totalparticipants had diabetes.

The study found that major coronary eventswere halved in people with diabetes on statintherapy. Total cholesterol was reduced by 27%,LDL cholesterol by 36%, triglycerides by 11%,and HDL cholesterol was increased by 7%.

� United Kingdom ProspectiveDiabetes Study (UKPDS)

The UKPDS recruited over 5000 patients withnewly-diagnosed type 2 diabetes between 1977and 1991 and followed them for 10 years.

The study confirmed that when people withtype 2 diabetes aggressively lowered bloodglucose (maintaining HbA1c levels around 7%),their risk of blindness and kidney failure fell by25%. In a group of overweight people treatedwith an oral hypoglycaemic agent (metformin)the impact on microvascular complications wasnot as strong, but there was a significantreduction in the risk of a fatal or non-fatalheart attack (37%) and all-cause mortality(36%). When high blood pressure wasaggressively tackled, major reductions in therisk of stroke (44%) and heart failure (56%)were achieved in addition to the eye andkidney benefits.

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� Veterans Affairs High-DensityLipoprotein CholesterolIntervention Trial (VA-HIT)

The objective of the VA-HIT study was toassess the effect of fibrate therapy on mortalityand the risk of a major coronary event inpeople with coronary heart disease and near-normal LDL cholesterol but low HDLcholesterol. 25% of the participants haddiabetes.

The study found that by increasing HDLcholesterol by just under 8% and decreasingtriglycerides by 25%, the risk of a majorcardiovascular event was cut by 22% in peoplewith diabetes. This was the first trial todemonstrate a diminished risk of cardiac eventsfrom an intervention that raised HDL levels butdid not reduce LDL levels.

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Glossary

Glossary

ALBUMINURIA

A condition where too much protein (albumin)is secreted in the urine, usually an indication ofkidney disease. When only tiny amounts ofalbumin are excreted this is calledmicroalbuminuria.

ANGINA

Discomfort in the chest caused by aninadequate supply of blood to the heartmuscles. Can be stable or unstable.

ANGIOPLASTY

Surgery whereby a balloon is inflated inside ablocked artery to open it up.

ANGIOTENSIN CONVERTING ENZYME (ACE)

INHIBITOR

A type of drug used for blood pressurecontrol and heart failure. Studies indicatethat it may also help prevent or slow theprogression of kidney disease in people withdiabetes.

ARTERY

A vessel carrying blood from the heart tovarious parts of the body.

ATHEROMA

Fatty material that can build up within the wallsof the arteries.

ATHEROSCLEROSIS

Hardening and thickening of the walls of thearteries as a result of deposits of atheromaon their inner lining. This build-up of atheromamay slow down or stop blood flow.

AUTONOMIC NEUROPATHY

Disease of the nerves affecting mostly internalorgans such as the bladder, the cardiovascularsystem, the digestive tract and the genital

organs. These nerves are not under a person’sconscious control and function automatically.

BETA BLOCKER

Drugs that block the action of the hormoneadrenaline that makes the heart beat faster andmore vigorously, thereby relieving stress to theheart muscle. Beta blockers are often used toslow the heart rate, lower blood pressure,prevent angina attacks, prevent irregularheartbeats and reduce the risk of heartattacks in people who have already had one.

BETA CELL

Beta cells are found in the Islets of Langerhansin the pancreas. They produce and releaseinsulin.

BLOOD PRESSURE

A measure of the force of the blood beingpushed by the heart through the arteries. Thispressure is created when the heart beats,forcing blood around the body and also by theelastic resistance of the arteries themselves.Blood pressure is written as two numbers. Thehigher number (systolic) shows the pressurecreated by the heart contracting or pumpingout the blood. The lower number (diastolic)indicates the pressure when the heart isrelaxing between beats. The pressure ismeasured on a blood pressure gauge inmillimetres of mercury (mm Hg).

BLOOD VESSEL

An artery, vein or capillary.

BODY MASS INDEX (BMI)

A key index for assessing body weight inrelation to height. The BMI is a person’s weightin kilograms (kg) divided by their height inmeters (m) squared. In the West a person isconsidered overweight when his/her BMI is

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above 25, obese when it is above 30 andseverely obese when it is above 35. In Asia therecently-recommended corresponding BMIs are23, 25 and 30 respectively.

BYPASS SURGERY

An operation whereby a blood vessel is takenfrom another part of the body and is used toredirect the flow of blood around a blocked ornarrowed part of a heart vessel.

CALCIUM CHANNEL BLOCKER

A drug used to treat angina and to lowerblood pressure.

CAPILLARY

Capillaries are the smallest of the bloodvessels. They join the arteries to the veins.

CARDIOVASCULAR DISEASE

Cardiovascular diseases are defined as diseasesand injuries of the circulatory system: theheart, the blood vessels of the heart, and thesystem of blood vessels throughout the bodyand to (and in) the brain. Stroke is the resultof a blood flow problem within, or leading to,the brain and is considered a form ofcardiovascular disease.

CAROTID ARTERY

The two carotid arteries are located on eachside of the front of the neck. These arteriesprovide the principal blood supply from theheart to the head and neck.

CENTRAL OBESITY

An abnormal accumulation of fat around theabdomen which can be assessed by measuringthe ratio of the waist to the hip circumference.This form of obesity is strongly associated withcardiovascular and diabetes risk. Also known asvisceral or abdominal obesity.

CEREBROVASCULAR DISEASE

Damage to the blood vessels in the brain,which may result in a stroke.

CHOLESTEROL

A waxy, fat-like substance used by the body tobuild cell walls. It is either produced in the liveror absorbed from the animal fats we eat.

Cholesterol is carried in the blood stream byparticles called lipoproteins. When totalcholesterol is measured in the blood, itincludes cholesterol carried by low-densitylipoproteins (LDL) and high-densitylipoproteins (HDL).

CIRCULATORY SYSTEM

The system composed of the heart and bloodvessel tree.

CORONARY ARTERY

The coronary arteries are blood vessels thatdeliver oxygenated blood to the muscle of theheart.

CORONARY ARTERY DISEASE

Coronary artery disease begins whenatheroma is deposited within a coronaryartery.

CORONARY HEART DISEASE

Any disease of the heart caused by coronaryartery disease, although it usually refers toheart attack and angina.

C-REACTIVE PROTEIN

C-reactive protein is a protein whose plasmaconcentrations increase (or decrease) by 25%or more during inflammatory disorders.

DEMENTIA

Significant loss of intellectual abilities such asmemory and judgement, severe enough tointerfere with social or occupationalfunctioning.

DIABETES MELLITUS

Diabetes mellitus is a chronic condition thatarises when the pancreas does not produceenough insulin or when the body cannoteffectively use the insulin produced. This causeshyperglycaemia which seriously damagesmany of the body’s systems, especially theblood vessels and nerves. There are two maintypes of diabetes: type 1 diabetes and type 2diabetes.

DIGITALIS

A plant-based drug used to treat heart failureand certain abnormalities of the heart rhythm.

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DIURETIC

Diuretics increase the output of water and saltin the urine. They are used to treat heartfailure and to lower blood pressure.

DYSLIPIDAEMIA

Abnormal levels of lipids (fats) in the blood.

ELECTROCARDIOGRAM (ECG)

A test using electrodes placed on the chest,arms and legs to record the rhythm andelectrical activity of the heart.

ENDOTHELIUM

The layer of flat cells that lines the cavities ofthe heart and of the blood and lymph vessels.

EXERCISE CARDIAC STRESS TESTING

The most widely used screening test for heartdisease. The patient exercises on a treadmill,whose speed and elevation increasesprogressively. During this test the heart rate,heart rhythm, electrocardiogram and bloodpressure are monitored.

FEMORAL ARTERY

The femoral arteries provide the blood supplyto the lower limbs.

FIBRATE

Fibrates are cholesterol-lowering drugs thatare primarily effective in loweringtriglycerides and, to a lesser extent, inincreasing high-density lipoproteincholesterol levels.

FOOT ULCER

A break in the skin or a deep sore that canoccur in people with diabetes because of nerveand/or vessel damage to the foot.

GANGRENE

The death of body tissue due to the loss ofblood supply to that tissue, sometimespermitting bacteria to invade it and accelerateits decay.

GESTATIONAL DIABETES

A carbohydrate intolerance of varying degreesof severity with onset or first recognitionduring pregnancy. Gestational diabetes develops

during some cases of pregnancy but usuallydisappears when pregnancy is over. Howeverwomen who have had gestational diabetes areat a much greater risk of developing type 2diabetes at a later stage in their lives.

HAEMOGLOBIN A1C (HBA1C)

Haemoglobin (Hb) is the protein in the redblood cells which carries oxygen to the cells.HbA1c corresponds to a small part of Hb(normally less than 6%) which joins with theglucose present in the blood. Because theglucose stays attached to it throughout the lifeof the red cell (about three months), a test tomeasure HbA1c reflects what the person’saverage blood glucose level was for that periodof time.

HEART ATTACK

Also called myocardial infarction; results frompermanent damage to an area of the heartmuscle. This happens when the blood supply tothe area of the heart is interrupted because ofnarrowed or blocked blood vessels. In themajority of cases this is due to coronaryartery disease.

HEART FAILURE

Heart failure occurs when the heart musclesbecome overworked from the strain of pushingblood through narrow, hard blood vessels.

HIGH-DENSITY LIPOPROTEIN (HDL)

Cholesterol is carried in the blood stream bylipoproteins. The high-density lipoprotein(HDL) recovers cholesterol from cells, vesselwalls and other lipoproteins and thus tends toprevent or reverse the build-up of plaque inthe arteries. That is why HDL cholesterol isconsidered ‘good’ or ‘protective’.

HOMOCYSTEINE

Researchers believe that homocysteine maycontribute to the build-up of fatty substancesin the arteries, increase the stickiness ofblood platelets (clotting), and make bloodvessels less flexible and less able to widen topermit increased blood flow.

HYPERGLYCAEMIA

A raised level of glucose in the blood.

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HYPERTENSION

Persistently elevated blood pressure.

IMPAIRED FASTING GLYCAEMIA (IFG)

Raised fasting levels of glucose.

IMPAIRED GLUCOSE TOLERANCE (IGT)

Blood glucose levels that are higher thannormal but below the level of a person withdiabetes.

IMPOTENCE

The loss of a man’s ability to have an erectpenis, often referred to as erectile dysfunction.

INSULIN

A hormone whose main action is to enable thebody cells to absorb glucose from the bloodand use it for energy. It also regulates lipid andprotein metabolism. Insulin is produced by thebeta cells in the pancreas.

INSULIN RESISTANCE

A state in which a given level of insulinproduces a less than expected biological effect.

INTERMITTENT CLAUDICATION

A cramp-like pain due to ischaemia mostly inthe calf and leg muscles, brought on by walkingand relieved by rest.

ISCHAEMIA

Ischaemia is a usually temporary shortage ofoxygen in a part of the body.

KETONE

Ketones are chemicals that the body produceswhen there is not enough insulin in the bloodand it must break down fat for its energy.When ketones build up in the blood, the bodydisposes of them via the urine.

LEFT VENTRICULAR HYPERTROPHY

When the heart muscle of the left ventriclebecomes abnormally thickened.

LIPOPROTEIN

A lipoprotein is a particle composed of proteinand lipids that transports the lipids in thebloodstream and lymph system. Lipoproteinsare of varying size and density and contain

different amounts of lipids and proteins. Seehigh-density lipoprotein and low-densitylipoprotein.

LIPOPROTEIN (A)

High levels of Lipoprotein (a) or Lp(a), arethought to increase the risk of coronary heartdisease by preventing the breakdown of clotsthat may form on atherosclerotic plaques.

LOW-DENSITY LIPOPROTEIN (LDL)

Cholesterol is carried in the blood stream bylipoproteins. The low-density lipoprotein(LDL) carries most of the cholesterol from theliver to the cells. If there is an excess ofcholesterol or it cannot be properly deliveredto the cells, LDL cholesterol tends toaccumulate in the vessel walls, where it canlead to damage and contribute to thedevelopment of atherosclerosis. ThereforeLDL cholesterol is considered ‘bad’ cholesterol.

MACROANGIOPATHY

Disease of the large blood vessels. Usuallyrefers to the complications of diabetesresulting from atherosclerosis.

METABOLIC SYNDROME

A condition whereby a series of clinicalproblems such as central obesity, abnormalglucose tolerance, lipid abnormalities,hypertension, insulin resistance andmicroalbuminuria tend to be present in thesame subject. This syndrome is considered avery important risk factor for cardiovasculardisease.

METFORMIN

An oral hypoglycaemic agent that decreasesglucose production from the liver and glucoseabsorption from the gut. It also slightlydecreases insulin resistance.

MICROALBUMINURIA

See albuminuria.

MICROANGIOPATHY

Disease of the very small blood vessels.Usually refers to the chronic complications ofdiabetes resulting from damage to the

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capillaries (such as retinopathy ornephropathy).

NEPHROPATHY

Diabetic nephropathy (kidney damage) resultsin large amounts of urine protein andhypertension, and is slowly progressiveleading to kidney failure. It usually does notoccur until many years of diabetes and can bedelayed by tight control of blood glucose.

NEUROPATHY

Diabetic neuropathy refers to damage to thenerve fibres caused by diabetes. Long nervesare most affected and so the process is usuallyfirst noticed in the feet with a numbness andloss of sensation.

NITRATES

Drugs that dilate blood vessels. They areeffective in treating angina.

ORAL HYPOGLYCAEMIC AGENTS

Drugs that lower the level of glucose in theblood. They work for some people with type 2diabetes if their pancreas still producessome insulin. They can help the body in severalways such as causing the cells in the pancreasto release more insulin.

PANCREAS

The pancreas is an organ situated behind thelower part of the stomach which producesinsulin.

PERIPHERAL VASCULAR DISEASE

Peripheral vascular disease refers to diseases ofblood vessels outside the heart and brain. Itoften involves a narrowing of the vessels thatcarry blood to leg muscles.

RETINOPATHY

Retinopathy is a disease of the retina of the eyewhich may cause visual impairment andblindness.

REVASCULARIZATION

The procedure by which a blocked vessel canbe either dilated (angioplasty) or bypassed(bypass surgery).

SILENT ISCHAEMIA

Silent ischaemia occurs when someoneexperiences an episode of ischaemia withoutknowing it as no pain is involved.

STABLE ANGINA

Stable angina occurs when individualsexperience angina on a regular basis and canbe given medication to treat it.

STATIN

A class of drug that lowers cholesterol.

STROKE

A sudden loss of function in part of the brainas a result of the interruption of its bloodsupply by a blocked or burst artery.

SUDDEN DEATH

This term refers to the death of a personresulting from an abrupt loss of heart function.

TRANSIENT ISCHAEMIC ATTACK

‘Mini-strokes’ that produce stroke-likesymptoms and signs which clear completelywithin 24 hours. Transient ischaemic attacks arestrong predictors of stroke.

TRIGLYCERIDE

The major form of fat made in the liver. Atriglyceride consists of three molecules of fattyacid combined with a molecule of the alcoholglycerol. Most of the fat we eat is composed oftriglycerides. The rest is cholesterol.

TYPE 1 DIABETES

Type 1 diabetes occurs most frequently inchildren and adolescents, but is now alsoincreasingly found in adults. About 10% ofpeople with diabetes have type 1. Thesymptoms vary in intensity and includeexcessive thirst, excessive passing of urine,weight loss and lack of energy. Insulin is a life-sustaining medication for people with type 1diabetes, who require daily insulin injections forsurvival.

TYPE 2 DIABETES

About 90% of people with diabetes have type 2,which occurs mainly in adults. Some peoplewith type 2 diabetes have no early symptoms

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and are only diagnosed several years after theonset of the condition, when various diabeticcomplications are already present. Type 2diabetes is usually controlled by diet, exerciseand oral hypoglycaemic agents. Insulininjections may also be required.

UNSTABLE ANGINA

If an attack of angina differs from a person’sregular pattern (stable angina), appearingsuddenly, with greater intensity or when at rest,it is considered unstable. It may warn of animpending heart attack.

VEIN

A vessel carrying blood back from variousparts of the body to the heart.

VERTEBRAL ARTERY

The two vertebral arteries follow the vertebralcolumn at the back of the neck. They carryblood from the heart to the brain.

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