SC Diabetes and Cardiovascular Disease V1

Short Course:
Diabetes and Cardiovascular Disease
IDF Short Course

Diabetes and Cardiovascular Disease 1
www.idfdiabeteschool.org
Learning Objectives
After completing this module, you should be able to:

 Discuss the overview of diabetes and cardiovascular disease
 Review the different types of cardiovascular complications
 Describe the pathophysiology of cardiovascular complications in
diabetes
 Discuss the epidemiology of coronary heart disease,
cerebrovascular disease and peripheral vascular disease
 List the potential risk factors associated with cardiovascular
complications
 Identify the screening and diagnostic tests for detecting
cardiovascular complications in people with diabetes
 Discuss the management strategies for cardiovascular
complications
T1DM, Type 1 diabetes mellitus; T2DM, Type 2 diabetes mellitus
IDF Short Course

Overview of Diabetes and Cardiovascular
Disease
IDF Short Course

Introduction
Cardiovascular Disease Triad1
Cerebrovascular Coronary Peripheral Clinical manifestations of CVD in

disease heart disease vascular disease diabetes2
Angina (stable and

unstable)
Silent ischaemia
Myocardial infarction
Sudden death
Heart failure
CVD complications are more prevalent in people

with T2D.1
CHD: coronary heart disease; CVD: cardiovascular disease; PVD: peripheral vascular
disease; T1D: type 1 diabetes mellitus; T2D: type 2 diabetes mellitus.
IDF Short Course

Diabetes and heart failure
Diabetes is an important risk factor for heart failure. People with diabetes have a 2-to 5-fold
higher risk of developing heart failure 1
Risk factors for heart failure2 Heart failure is associated with

multiple risk factors3
Diabetes confers 60–80% greater probability of CV death and all‑cause mortality in those with
established HF4,5
CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; HFpEF, heart failure with preserved ejection
fraction; HFrEF, heart failure with reduced ejection fraction; IL, interleukin, LV, left ventricular; TNF, tumor necrosis factor
IDF Short Course

Diabetes and heart failure
Age-associated incidence of heart failure increase in patients with diabetes.
HF incidence by age group1 CV death or HHF in patients with or without

diabetes based on ejection fraction2
HRs refer to the risk of CV death or HHF in

patients with diabetes versus non-diabetes
CV, cardiovascular; EF, ejection fraction; HHF, hospitalisations for heart failure HF, heart failure; rEF, reduced ejection fraction
IDF Short Course

Pathophysiology of Macrovascular
Complications in Diabetes
IDF Short Course

Atherosclerosis – A Potential Risk Factor
for Diabetic Complications
Pathophysiology of Cardiovascular Disease and Diabetes1,2
T2D is a major and independent risk factor for both microvascular and macrovascular
complications1
Endothelial dysfunction is common to
microvascular and macrovascular events2
IDF Short Course

Atherosclerosis – A Potential Risk Factor
for Diabetic Complications
Pathophysiology of Cardiovascular Disease and Diabetes1
Endothelial dysfunction drives atherosclerotic progression

Visceral adiposity is related to inflammation, insulin resistance, dyslipidaemia and atherosclerosis
Atherosclerosis is accelerated in T2D by hyperglycaemia, insulin resistance, inflammation and diabetic dyslipidaemia 2
Hypertension is a strong driver of CV outcomes in diabetes
Altered lipid profile in T2D is most likely to be due to insulin resistance 3
IL-6: Interleukin 6; IRS-1: Insulin receptor substrate 1; LDL: low-density lipoproteinPI3K: Phosphoinositide 3-kinase; TNF-: Tumor
necrosis factor alpha T2D, type 2 diabetes mellitus
IDF Short Course
Inhibition of Protective Factors
Glucose and Lipid Metabolites1
Inhibit
Anti-
inflammatory Antioxidants Insulin PDGF VEGF APC
factors
APC: activated protein C;

PDGF: platelet-derived
growth factor; VEGF:
vascular endothelial growth Vascular Injury and Disease
factor.
IDF Short Course
Pathophysiology of heart failure
• Hyperglycaemia and insulin resistance are important contributing factors which cause HF in
patients with T2D1
Pathophysiology of HF in T2D 1
RAS: renin angiotensin system.

IDF Short Course
Epidemiology of CVD in People With Diabetes
IDF Short Course

Incidence and Prevalence of CHD
• Cardiovascular diseases are the most prevalent cause of mortality and morbidity among people with T1D and
T2D
• Two to four fold increase in the risk of developing CHD 1
• 41% of the middle-aged people with diabetes living in high- and middle-income countries have CHD 2
Life expectancy is reduced by ~12 years in diabetes Diabetes confers significant CV risk; combination of
patients with previous CVD 3 diabetes and history of MI further increases risk 4
No diabetes, no prior MI
Prior MI
A person living with T2D and CVD may Despite improved standard of care, patients
die 12 years younger than someone with T2D remain at increased risk of CV
without T2D and CVD3 mortality5
CHD: coronary heart disease; MI, myocardial infarction; T1D: type 1 diabetes
mellitus; T2D: type 2 diabetes mellitus.
IDF Short Course

Incidence and Prevalence of
Cerebrovascular Diseases
Diabetes increases the risk of stroke by 150% to 400% 1
10-fold higher risk of stroke in population <55 years of

age2
Diabetes increases the risk of
 Stroke-related dementia by more than three folds

 Recurrent stroke by two folds
 Total and stroke-related mortality1
IDF Short Course

• Diabetes increases the risk of PVD by two to four folds

• Intermittent claudication and amputation are commonly seen symptomatic forms of PVD 1
Estimated annual direct costs of diabetic limb complications in comparison to the annual
direct costs of the five most costly cancers in the United States
Estimated annual direct costs of diabetic

limb complications are higher than the
annual costs of cancers2
Adapted from: Barshes NR, et al. 2013.2
Presence of diabetes increased the risk of intermittent claudication by 3.5 folds in men and 8.6 folds in
women1
PVD: peripheral vascular disease.

IDF Short Course
Risk Factors
IDF Short Course

Risk Factors for CVD
Non-modifiable Risk Factors1
Age Sex
 Significantly higher risk in men >45 years and • Men are at a higher risk than women of the
women >55 years same age
• Higher risk in women post menopause
Family history
Ethnicity
 People with parents or siblings with a history of
premature development of cardiovascular disease  African Americans are at a higher risk than
Europeans
IDF Short Course

Risk Factors for CVD (Cont’d)
Modifiable Risk Factors1-3
 Major risk factor for  Abnormal lipid profile  Causes insulin  Increases the risk of
cardiovascular disease consisting of high resistance early development of
levels of total cardiovascular diseases
cholesterol,
triglycerides and LDL-
C and/or low levels of
HDL-C
Hypertension Dyslipidaemia Obesity Hyperglycaemia
 Increases the risk of  Diet rich in saturated  Increases the risk of

heart disease and fats increases the risk heart disease and
stroke by 50% of heart disease and stroke
stroke
Physical Unhealthy diet Cigarette

inactivity smoking
LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol.

IDF Short Course
Prevalence of Risk Factors for CVD
Prevalence of Modifiable Risk Factors for Cardiovascular Disease in People With Diabetes 1
HDL: high-density lipoprotein; T2D: type 2 diabetes mellitus.
IDF Short Course

Screening and Diagnostic Tests
IDF Short Course

Cardiovascular Risk Calculator – UKPDS
Risk Engine
• The IDF recommends calculating cardiovascular risk in people with T2D using prediction models that can
be applied to the diabetes population
• Includes the use of UKPDS risk engine 1 Uses equations to calculate2
• Incidence rates
• Probability of developing CHD complications
• Relative and absolute risk factors
• Multiple risk factors, which provide the overall
rate of the event
Provides an estimation of the risk and 95%

confidence interval in people with diabetes
without any incidence of non-fatal and fatal CHD
or stroke
Characteristics considered include2

• Age and sex
• Ethnicity
• Diabetes duration
• Presence of atrial fibrillation
• Smoking status
• Glycated haemoglobin (HbA1c) levels
• Systolic blood pressure
• Levels of total cholesterol and HDL-C
CHD, coronary heart disease; HbA1c, glycated haemoglobin; HDL-C, high-density lipoprotein-cholesterol; IDF, International Diabetes
Federation; T2D, type 2 diabetes mellitus; UKPDS, United Kingdom Prospective Diabetes Study.
IDF Short Course
Testing for CVD in People With Diabetes
Factors considered before selection of a particular modality for testing 1
• Gender
• Mobility Sensitivity and specificity of different tests in people with diabetes
• Exercise tolerance
• Availability
• Sensitivity
• Specificity
• Associated risk
 Helps identify  Less sensitive in asymptomatic people with

people with left lower pretest probability, in people with
Exercise ECG main or diabetes who are unable to reach the expected
significant multi- exercise capacity due to obesity, peripheral
vessel CHD neuropathy, decreased physical conditioning or
other co-morbidities and in women
 Provides additional  Poor specificity and  Limitations include high

Stress information regarding negative predictive value cost and lack of operator
Echocardiography any prior infarcts and in population with expertise
ventricular dysfunction diabetes
CVD: cardiovascular disease; CHD: coronary heart disease; CT: computed tomography; ECG: electrocardiogram.
IDF Short Course
Testing for CVD in People With Diabetes
(Cont’d)
Stress Nuclear • Most widely used modality for diagnosing CHD in people with diabetes.
Imaging1 • Provides information regarding coronary flow at rest detected with exercise
or stimulated stress and regional wall motion
 Provides useful information  Shown reduced sensitivity and specificity

CTCA about the lumen of the in people with diabetes due to
vasculature and the arterial calcifications
wall
Coronary Artery  The American Heart Association (AHA) considers the measurement of the
Calcium Score coronary artery calcium score as a good predictor of CV events in asymptomatic
individuals more than 40 years of age
Sensitivity and specificity of provocative tests in women with diabetes
SPECT and stress echocardiography have better sensitivity and specificity than exercise ECG in women
AHA: American Heart Association; CHD: coronary heart disease; CTCA: computed tomography coronary angiogram; ECG:
electrocardiogram; SPECT: stress single photon emission computed tomography.
IDF Short Course
CVD Risk Stratification and Test Selection
Suggested Algorithm for Investigation of CVD in People With Diabetes 1
Advanced renal dysfunction
CABG: coronary artery

bypass graft surgery;
CMR: cardiac magnetic
resonance; CTCA:
computed tomography
coronary angiogram;
CVD: cardiovascular
disease; ECG:
Perfusion CMR Perfusion CMR Perfusion CMR echocardiogram; LBBB:
left bundle branch
block; UKPDS: United
Kingdom Prospective
+ CABG Diabetes Study.
IDF Short Course

Additional Vascular Markers
Additional Vascular Markers1
– ABI
– Carotid IMT
– Detection of carotid plaques
– Arterial stiffness measured by pulse wave velocity
– CAN
Recommendations for cardiovascular risk assessment in diabetes 1
Adapted from: ESC

guidelines on diabetes,
pre-diabetes, and
cardiovascular diseases
developed in
collaboration with the
EASD – summary, 2014.
ABI: ankle-brachial index; CAN: cardiac autonomic neuropathy; CVD: cardiovascular

disease; DM: diabetes mellitus; IMT: intima media thickness.
IDF Short Course

Treatment and Management
IDF Short Course

Multifactorial approach
A multifactorial approach is very important in patients with T2D
Lifestyle Blood pressure Control of

interventions management hyperglycaemia
Control of
Platelet stabilisation
dyslipidaemia
Adapted from: ESC guidelines on cardiovascular disease prevention in clinical

practice, 2016.
IDF Short Course

Lifestyle interventions
ESC Guidelines on cardiovascular disease prevention-Diabetes 1
Weight control is an important component.
A predominance of fruits, vegetables, wholegrain cereals and low-fat protein sources along with salt
restriction in essential.
Limit saturated and trans fats and alcohol intake, monitor carbohydrate consumption and increase
dietary fibre.
A Mediterranean-type diet is recommended, where fat sources are derived primarily from
monounsaturated oils.
Smoking should be strongly discouraged.
A combination of aerobic and resistance exercise training is effective in the prevention of the
progression of DM
Adapted from: ESC guidelines on cardiovascular disease prevention in clinical practice, 2016.
IDF Short Course

Management of Hypertension
Presence of hypertension in people with diabetes increases the CVD risk by four folds1
BP targets should be considered regardless of overall CV risk score in patients with T2D. 2
• A systolic target of <140 mmHg should be considered to lessen the risk of overall
mortality
• In people >80 years of age, targets should be set higher, aiming for <150/90 mmHg,
unless renal impairment is present.
• An ACE-I or an angiotensin receptor blocker (ARB), where tolerated, should always be
included as first-line therapy
• Combination treatment is commonly needed to lower BP effectively in DM
In the UKPDS, intensive blood pressure reduction was associated with a significant reduction in stroke and
death3
ACE-I: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blockers; DM: diabetes mellitus
IDF Short Course

Lipid-lowering therapy
Besides LDL, elevated triglyceride levels and lower HDL-C levels increase the CVD risk 1,2
• Treatment with simvastatin 40 mg reduced the risk of CAD and stroke in people with DM
and individuals without DM who had no prior AMI or angina pectoris (Heart Protection
Study)
• Stain therapy along with ezetimibe has been shown to have a benefit in people with T2D.
• PCSK9 inhibitors are also equally efficacious in lowering LDL-C in people with T2D.
• Special consideration is required while prescribing lipid-lowering agents in older people
with DM (>85 years)3
AMI, acute myocardial infarction; CVD: cardiovascular disease; DM: diabetes mellitus; HDL-C: high-density lipoprotein cholesterol;
LDL-C: low-density lipoprotein cholesterol; T2D: type 2 diabetes mellitus.
IDF Short Course

Management of Hyperglycaemia
Adequate control of blood glucose levels helps in reducing

CVD risk1
• Metformin is considered the first line therapy

• Meta-analyses have shown that intensive glucose control achieved significant
reductions in non-fatal AMI and CAD events.
• SGLT2 inhibitor empagliflozin demonstrated substantial reductions in CVD death
by 38% and all-cause mortality by 32% as well as in hospitalisation for HF by
35%, as compared with standard care, suggesting an early intervention with
SGLT2 inhibitor in the course of management of patients with DM and CVD.
AMI, acute myocardial infarction; CAD, coronary artery disease; CVD: cardiovascular disease;
DM: diabetes mellitus; T2D: type 2 diabetes mellitus.
IDF Short Course

Antiplatelet Therapy in People With
Diabetes
Platelet aggregation is the major causative factor in the development of ACS 1
• Benefits of antithrombotic therapy (mainly aspirin) has been

demonstrated inin people with T2D with clinically established CAD,
cerebrovascular disease or other forms of thrombotic disease, with a
25% reduction in risk of CV events (Antiplatelet Trialists’
Collaboration meta-analysis)1
Studies conducted in people without diabetes post-ACS showed more efficacy with prasugrel and
ticagrelor than clopidogrel2-4
ACS: acute coronary syndrome; CVD: cardiovascular disease; DM: diabetes mellitus; RCT, randomized controlled
trails
IDF Short Course

Management of Cerebrovascular Disease
 Prevent risk factors such as hyperglycaemia from developing complications in
Level 1 the brain vasculature
 Aggressive glycaemic control and reduction of blood pressure to the normal

range
Level 2
 Improve the cerebral blood flow to reduce the risk of mortality after a stroke
Level 3 event in people with diabetes
• Lifestyle modifications, use of glucose-lowering agents and insulin, and antihypertensive agents can prevent
recurrences
• Atherosclerotic progression can be slowed with the use of antiplatelet therapy such as aspirin or clopidogrel
and aggressive statin use
• Combination therapy with aspirin and clopidogrel should be avoided due to the increased risk of adverse
events
• Carotid endarterectomy should be considered in people who had an ischaemic stroke and have ≥70% carotid
stenosis1,2
IDF Short Course

Management of Peripheral Vascular Disease
People with diabetes have a two to four fold
higher risk of LEAD1
IDF recommends revascularisation as an

alternative to limb amputation2
ABI: ankle-brachial index; DM: diabetes

mellitus; LDL-C: low-density lipoprotein
cholesterol; LEAD: lower extremity artery
disease; PAD: peripheral artery disease.
IDF Short Course

Summary
 Macrovascular complications in diabetes result in the development of

cardiovascular complications such as CHD, cerebrovascular disease and
PVD.
 Diabetes is associated with a
o Two to four-fold increase in the risk of developing CHD
o 150% to 400% increase in the risk of stroke
o Two to four- fold increase in the risk of PVD
 CVDs are the most prevalent cause of mortality and morbidity among people
with T1D and T2D.
 The non-modifiable risk factors include age, sex, family history and ethnicity.
 The modifiable risk factors include hypertension, dyslipidaemia, obesity,
hyperglycaemia, physical inactivity, unhealthy diet and smoking.
 IDF recommends calculating cardiovascular risk in people with T2D using
prediction models that can be applied to the diabetes population, including
the use of UKPDS risk engine.
IDF Short Course

Summary (cont.)
 The provocative tests for screening of underlying CVD in people with diabetes
include:
o Exercise ECG
o Stress echocardiography
o Stress nuclear imaging or perfusion CMR
o CTCA
o Coronary artery calcium score
 A multifactorial approach consisting of aggressive management of blood
pressure, hyperglycaemia, dyslipidaemia, platelet stabilisation and lifestyle
interventions should be implemented in people with T2D.
 Use of pharmacotherapeutic drugs such as ACE-I, ARBs, statins and
antiplatelet agents should be considered when appropriate.
IDF Short Course


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Short Course:

Diabetes and Cardiovascular Disease

IDF Short Course

After completing this module, you should be able to:

IDF Short Course

IDF Short Course

Cardiovascular Disease Triad1

Cerebrovascular Coronary Peripheral Clinical manifestations of CVD in

Angina (stable and

CVD complications are more prevalent in people

IDF Short Course

Risk factors for heart failure2 Heart failure is associated with

IDF Short Course

HF incidence by age group1 CV death or HHF in patients with or without

HRs refer to the risk of CV death or HHF in

IDF Short Course

IDF Short Course

IDF Short Course

Endothelial dysfunction drives atherosclerotic progression

Glucose and Lipid Metabolites1

APC: activated protein C;

RAS: renin angiotensin system.

IDF Short Course

IDF Short Course

Diabetes increases the risk of stroke by 150% to 400% 1

10-fold higher risk of stroke in population <55 years of

Diabetes increases the risk of

 Stroke-related dementia by more than three folds

IDF Short Course

Incidence and Prevalence of CHD

• Diabetes increases the risk of PVD by two to four folds

Estimated annual direct costs of diabetic

Adapted from: Barshes NR, et al. 2013.2

PVD: peripheral vascular disease.

IDF Short Course

IDF Short Course

Hypertension Dyslipidaemia Obesity Hyperglycaemia

 Increases the risk of  Diet rich in saturated  Increases the risk of

Physical Unhealthy diet Cigarette

LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol.

HDL: high-density lipoprotein; T2D: type 2 diabetes mellitus.

IDF Short Course

IDF Short Course

Provides an estimation of the risk and 95%

Characteristics considered include2

 Helps identify  Less sensitive in asymptomatic people with

 Provides additional  Poor specificity and  Limitations include high

 Provides useful information  Shown reduced sensitivity and specificity

Sensitivity and specificity of provocative tests in women with diabetes

Advanced renal dysfunction

CABG: coronary artery

IDF Short Course

Recommendations for cardiovascular risk assessment in diabetes 1

Adapted from: ESC

ABI: ankle-brachial index; CAN: cardiac autonomic neuropathy; CVD: cardiovascular

IDF Short Course

IDF Short Course

A multifactorial approach is very important in patients with T2D

Lifestyle Blood pressure Control of

Adapted from: ESC guidelines on cardiovascular disease prevention in clinical

IDF Short Course

ESC Guidelines on cardiovascular disease prevention-Diabetes 1

Weight control is an important component.