DIABETES AND CARDIOVASCULAR DISEASE - THE CONTINUUM

DIABETES
and
CARDIOVASCULAR DISEASE
The continuum…
Dr.O.Adikesava Naidu M.D.,D.M.,FACC
Assosciate Professor,Dept. of Cardiology,
Osmania General Hospital, Hyderabad.
Consultant, YASHODA HOSPITALS, Somajiguda.

Diabetes…..the CVD equivalent
“From the point of view of cardiovascular disease it is appropriate
to say, Diabetes is a cardiovascular disease.”
- AHA Scientific Statement Diabetes and Cardiovascular disease.
Circulation 1999;100:1134-1146

Discovery of
Insulin*
The Miracle
“Drug ??”
1921
Charles Herbert Best
Sir Frederick Grant Banting
University of Toronto,CANADA
From latin word
Insula
meaning islet/island

Leonard Thompson
First Person to Receive Insulin
Purified by John Clamp in 1922,
for his Type1 Diabetes at the age of 14.

The “unlucky” man – Clark Noble.
Prof.W.J.R Macleod
Professor in Physiology
Awardee of Nobel Prize in Medicine.
“Allowing for experiments in his laboratory”

On his discovery of Insulin….
Insulin is not a cure for diabetes; it is a treatment. It
enables the diabetic to burn sufficient carbohydrates, so
that proteins and fats may be added to the diet in
sufficient quantities to provide energy for the economic
burdens of life.
— Sir Frederick Grant Banting

s
First Insulin Vial
Insulin Syringe used for experiment by Best and Banting
First Manufacturer of Insulin.
Funded the Scientists

Tom Hanks Salma Hayek
Wasim Akram
Halle Berry

Introduction
 Diabetes, is one of the most common noncommunicable
diseases.
 It is an ongoing epidemic in many developing countries.
 Cardiovascular disease is the most common cause of death.
 Management of a Cardiovascular disease in Diabetics is of
great challenge for the physicians and cardiologists.

Contents
 1.Definition
 2.Epidemiology
 3.Types of diabetes
 4.Etiopathogenesis
 5.Special points
 6.Evaluation of patient with diabetes
 7.Management
 8.Prevention
 9.Take home message

Contents
 1.Definition
 2.Epidemiology
 5.Special points with regards to CVD
 6.Evaluation of patient with diabetes for CVD
 7.Management
 8.Prevention

Definition
Diabetes Mellitus is a metabolic disorder, characterized by chronic
hyperglycemia associated with disturbances of carbohydrate, fat and
protein metabolism due to absolute or relative deficiency in Insulin
secretion and/or action.
“Metabolic cum vascular disorder”

Contents
 1.Diabetes Mellitus definition
 2.Epidemiology
 5.Special points
 6.Evaluation of patient with diabetes
 7.Management
 8.Prevention

Epidemiology
 The prevalence of diabetes across the world has tripled during
the last three decades.
 Approx. 382 million people ( 0.05 % of world population)
have diabetes(world population 7.125 billions).
 Approx half of them are undiagnosed (178 million).
 Among adults (>20 yrs of age) 9.6%of population have
diabetes( 10.5% men,8.8%women).

Diabetes is a huge and growing problem, and the costs to
society are high and escalating
382 million people have
diabetes
By 2035, this number will rise
to 592 million
IDF ,Global burden of
diabetes ,2013

IGT to be given equal importance

5-20%
60-70%
20-25%
Most of them are in 40-59 yrs of age
IDF,2013 report

Almost half of all people with
diabetes live in just three
countries
China
India
USA

Across the world 548 billion USD --
11% of total health expenditure on adults.

5.1 million deaths in 2013
Every 6 seconds one person die of diabetes

 More than 79,000 children developed type1 diabetes in
2013.
 More than 21 million live births were affected by diabetes
during pregnancy in 2013.

Statistics in India
 More than 62 million Indians have diabetes. (ICMR-INDIAB)
 65.4 million as per IDF statistics (2013).
Projected to increase to 100 million by 2030.
 Present prevalence rates are 15-20% (2.3% in 1971) in urban areas,
10-12% (1.2% in 1971)in rural areas.
There is overwhelming rise of diabetes in rural areas compared to
urban areas in recent times.

Disease Burden of Diabetes Mellitus
• 2-4x increase in cardiovascular mortality.
• DM responsible for 25% of cardiac surgeries.
• Mortality in DM: 70% due to Cardiovascular disease.
• 2.5x increase risk of stroke
• Leading cause of blindness (12.5% of cases)
• Leading cause of ESRD (42% of cases)
• 50% of all non-traumatic amputations

Types of Diabetes
Type 1 diabetes Type 2 diabetes Gestational diabetes
• Lack of insulin
• Autoimmune
• Usually children
• Insulin resistance
• Lifestyle factors
• Usually adults
• Insulin resistance
• During pregnancy
• Risks to mother and
child
Other specific types
Monogenic – MODY
LADA

Risk Factors
 1.Hyperglycemia
 2.Impaired Glucose Tolerance
 3.Insulin Resistance
 4.Metabolic Syndrome
 5.Dyslipidemia
 6.Obesity (Diabesity)
 7.Hypertension
 8.Smoking,Alcoholism
 9.Genetic predisposition
 10.Environmental factors

What is the effect of hyperglycemia on
CVD ?

Hyperglycemia is toxic at several steps in the atherosclerosis process
Retnakaran R, Zinman B. Lancet 2008;371:1790-99.

There is a clear epidemiologic association between glycemic control and CVD
NEW ENGLAND JOURNAL OF MEDICINE March 4, 2010
Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Non-diabetic
Adults
Elizabeth Selvin, Michael Steffes, Hong Zhu, Kunihiro Matusushita, et al.
Data from 11,092 black and white
subjects in the ARIC trial
(Atherosclerosis Risk in
Communities)
Median follow approximately 14
years.

Despite clear epidemiology, controversy continues regarding the role
of glucose lowering to prevent coronary events
ADA position on glycemia
and macrovascular disease in
2010 Standards of Care
Guideline
ADA Standards of Care.
Diabetes Care 2010;33:S11-62

2011 ADA guideline
appropriately discusses
microvascular benefits of A1C <
7% while acknowledging lack of
proven macrovascular benefits at
the A1C values that were studied.

Three large trials of glycemic control published in 2008 failed to find
CVD benefit
Non-fatal MI significantly reduced 24% (p=0.001)
So hyperglycemia doesn’t matter to the heart?
Sklyer JS, et al. Intentive glycemic control and the prevention of cardiovascular events. A position statement of the
ADA/ACC/AHA. Diabetes Care 2009;32:187-92.

Failure to find benefit may have related to the A1C levels tested:
6.4% vs. 7.5% 6.3% vs. 7.0% 6.9% vs. 8.5%
So hyperglycemia matters to the heart but intense control (A1C < 7%) provides little additional
benefit over moderate control (A1C 7-8%)
Sklyer JS, et al. Intentive glycemic control and the prevention of cardiovascular events. A position
statement of the ADA/ACC/AHA. Diabetes Care 2009;32:187-92.

DECODE: IGT Increases Mortality Risk
Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe

HbA1c Predicts MI in Type 2 Diabetes
UKPDS 35

Fatal and Non-Fatal Myocardial Infarction
p<0.0001
14% decrease per 1% decrement in HbA1c
5
1
0.5
0 5 6 7 8 9 10 11
Updated mean HbA1c
Hazard ratio
UKPDS 35. BMJ 2000; 321: 405-12

Insulin Resistance: Associated
Conditions

The Metabolic Syndrome
Insulin
Resistance
Complex
Dyslipidemia
TG, LDL
HDL
Hypertension
Type 2 Diabetes
Disordered
Fibrinolysis
Endothelial
Dysfunction
Systemic
Inflammation
Athero-sclerosis
Visceral
Obesity
Adapted from the ADA. Diabetes Care. 1998;21:310-314;
Pradhan AD et al. JAMA. 2001;286:327-334.

How all these lead to DIABETES ?

Development of Type 2 Diabetes

Natural History of Type 2 Diabetes
Normal Impaired glucose
tolerance
Glucose
level
Time
Type 2 diabetes
Insulin
resistance
Insulin
production
b-cell
dysfunction

Advanced Glycation Endproducts

The effect of Diabetes on
Atherosclerosis/CAD

How is CAD Different in Diabetes ?
 > CAD extent
 Multi-vessel disease
 Distal disease – more difficult to revascularize
 Silent ischemia/MI
 Younger
 Women
 Worse outcomes despite revascularization
 Increased re-stenosis after PCI even with stents
 worse periop & long-term outcomes

Risk of Cardiovascular Events in Diabetics
Framingham Study
Age-adjusted
Biennial Rate Age-adjusted
Per 1000 Risk Ratio
Cardiovascular Event Men Women Men Women
Coronary Disease 39 21 1.5** 2.2***
Stroke 15 6 2.9*** 2.6***
Peripheral Artery Dis. 18 18 3.4*** 6.4***
Cardiac Failure 23 21 4.4*** 7.8***
All CVD Events 76 65 2.2*** 3.7***
Subjects 35-64 36-year Follow-up **P< .001,***P< .0001

Framingham Heart Study 30-Year Follow-Up:
CVD Events in Patients With Diabetes (Ages 35-64)
10
9
Men Women
20
11
19
38 9 6
3*
30
10
8
6
4
2
0
Age-adjusted annual rate/1,000
Total
CVD
CHD Cardiac
failure
Intermittent
claudication
Stroke
Risk
ratio
P<0.001 for all values except *P<0.05.
Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease. Ruderman N
et al, eds. Oxford; 1992.

Diabetic Cardiomyopathy
 First described by Ruber et al. 1972.
 Term coined by Ludwack.
 Diabetic cardiomyopathy is generally regarded as a unique
pathologic and clinical entity marked by diffuse myocardial
fibrosis and hypertrophy that may result in the emergence of
progressive LV dysfunction and CHF.
 Evidence of LV dysfunction in absence of structural heart
disease ( coronary,HTN,valvular,congenital) or other causes of
secondary cardiomyopathy.

Cont…
 Diastolic dysfunction > Systolic dysfunction.
 Common in both diabetes and prediabetes.
 Presence of microalbuminuria increases the likelihood of diabetic
cardiomyopathy.

Pathogenesis
 Multifaceted,multifactorial
 1.impaired calcium homeostasis
 2.activation of RAAS
 3.Increased oxidative stress.
 4.altered substrate metabolism – metabolic cardiomyopathy.
 5.mitochondrial dysfunction.
 6.increased apoptosis
 7.autonomic neuropathy
 8.microvascular disease and endothelial dysfunction.
 9.disordered copper metabolism

Cardiovascular Autonomic Neuropathy
Indicators
 Resting tachycardia
 Orthostatic hypotension
 Peripheral neuropathy
 Silent myocardial ischemia or MI
 QT prolongation
 HR responses to Valsalva,deep breathing,standing up
 BP responses to sustained handgrip,standing up.

Congenital heart disease in
Newborn of diabetic mothers
 Risk of congenital anomalies is estimated to be between 2.5-12%
 The incidence of malformations is the highest in the group where
mothers were on insulin at the time of conception.
 Respiratory problems >CV problems (structural congenital heart
defect and hypertrophic cardiomyopathy) .
 Congenital heart disease -5%.
 Common are VSD,TGA,Aortic stenosis.
 Truncus Arteriosus and DORV are also more prevalent in IDMs.
Paediatr Cardiol. 2000 Apr-Jun; 2(2): 17–23.

Evaluation of a patient with diabetes for CVD .
 ECG
 2D ECHO
 TMT
 Stress Echocardiography
 CAG
 PTCA - BMS/DES
 CABG
 Carotid stenting
 Peripheral angioplasty

Three points critical to understanding the
evidence base of the ADA guidelines for lipid
management:
1. The etiologic role of lipoproteins in atherosclerosis
2. The etiology of dyslipidemia as seen in patients with diabetes
3. The clinical outcomes literature in patients with diabetes

How unique is the lipid panel in a diabetic patient

1. Atherosclerosis is a lipoprotein driven process
Basic Science for Clinicians
Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis
Update and Therapeutic Implications
Ira Tabas, MD, PhD;
Kevin Jon Williams, MD;
Jan Borén, MD, PhD
Circulation, October 16th, 2007

Lipoproteins share structural homology
Chylomicrons, VLDL, IDL, LDL, HDL all share a basic biochemistry
Liver
T
G
VLDL
IDL
LDL
Lipase
enzymes
Lipase
enzymes
LDLc

Type
(%)
Fredrickson Classification of Dyslipidemia
Appearance of
serum
Elevated
particles
We look at this
Associated clinical disorders TC
T
G
I (~1%) Creamy top layer Chylomicrons,
VLDL
Lipoprotein lipase deficiency,
apolipoprotein C-II deficiency
+ +++
IIa (10%) Clear LDL Familial hypercholesterolemia,
polygenic hypercholesterolemia,
nephrosis, hypothyroidism, familial
combined hyperlipidemia
++ ↔
IIb (40%) Clear LDL, VLDL Familial combined hyperlipidemia ++ +
III (~1%) Turbid IDL Dysbetalipoproteinemia + +
IV (45%) Turbid VLDL Familial hypertriglyceridemia, familial
combined hyperlipidemia, sporadic
hypertriglyceridemia, diabetes
+ ++
V (5%) Creamy top, turbid
bottom
Chylomicrons,
VLDL (remnants)
Diabetes + ++
Artery wall sees these

The primary atherogenic lipoprotein is LDL
lipoproteins of > 70 nm have limited transcytosis past the endothelium
Monocyte Vessel Lumen
LDL
LDL
Endothelium
Macrophage
MCP-1
Adhesion
Molecules
Foam Cell
Steinberg D et al. N Engl J Med 1989;320:915-924.
Modified
LDL Taken
up by
Macrophage
Intima
Nascent
chylomicron
Nascent
VLDL
Χ Χ
Artery wall

2. Dyslipidemia vs. Hyperlipdemia:
Prevalence in NHANES 2008 data: High TG or low HDLc more
common than high LDLc
Am Heart J 2008;156:112-119

Prevalence of Dyslipidemia is high in Type 2 Diabetes
Control of Lipids Patients With
Diabetes, %
Jacobs MJ, et al. Diabetes Res Clin Pract. 2005;70:263-269.
Patients Without
Diabetes, %
P Value
LDL-C
> 100 mg/dL
74.7 75.7 NS
HDL-C
< 40 mg/dL (men)
< 50 mg/dL (women)
63.7 40.0 < .001
Triglycerides
> 150 mg/dL
61.6 25.5 < .001
N = 498 adults (projected to 13.4 million) aged > or = 18 years with diabetes representative of the
US population and surveyed within the cross-sectional National Health and Nutrition Examination
Survey 1999-2000.

‘Dyslipidemia’ is a state of relative insulin resistance resulting in a conversion of adipose tissue
to an exocrine state. Excessive production of free fatty acids (FFA) increases hepatic VLDL
production
VLDL HDL
Hepatic lipase
Fat Cells Liver
Kidney
Insulin
CE
CETP
TG
CETP
Lipoprotein lipase
or hepatic lipase
Small, dense
LDL LDL
ApoA-I
TG
CE
 FFA
CE, cholesteryl esters; FFA, free fatty acids; TG, triglycerides.
Ginsberg HN. J Clin Invest. 2000;106:453–458.
↑ TG
↑ ApoB
↓ HDLc
↔ LDLc
XInsulin
resistance
Liver
IDL
 FFA
While LDLc is similar,
particle burden is heavier

LDL particle count vs. cholesterol content
To carry the same amount of cholesterol, a larger number of particles are needed
if they are smaller
Large, buoyant: 30-35 nm Small, dense: 25-30 nm
LDLc=115 mg/dl LDLc=115 mg/dl
apoB is a measure of number of atherogenic
lipoproteins (essentially VLDL, IDL, LDL).
Non-HDL is measure of cholesterol carried in
these same particles
LDLc measures cholesterol
carried in LDL and IDL

Summary: Patients with diabetes have
elevated TG and lower HDLc but also a
greater number of LDL particles which
confers greater risk at any measured LDLc
value
3. What are the data for LDLc lowering?

ADA guidelines: Major statin trials or sub-studies in diabetic
patients
Lancet 2004;364:685
Diabetes Care 2006;29:1220
Lancet 2003;361:2005
*Num. needed to treat (NNT) for moderate-high risk DM to avoid one death or MI:
3-50
ADA Standards of Care; Diabetes Care, January 2011

Reduction in 10-year CVD events with statin therapy in patients with diabetes:
Event reduction correlates with relative risk –more risk, more benefit
Endpoint: 10-year Fatal CHD/Non-fatal MI and LDL lowering
Relative Risk reduction ARR LDL reduction
 4S-DM 85.7 to 43.2% (50%) 42.5% 186 to 119 mg/dL (36%)
 ASPEN 20 35.1 to 23.2% (34%) 11.9% 112 to 79 mg/dL (29%)
 PS-DM 20 43.8 to 36.3% (17%) 7.5% 123 to 84 mg/dL (31%)
 CARE-DM 40.8 to 35.4% (13%) 5.4% 136 to 99 mg/dL (27%)
 TNT-DM 26.3 to 21.6% (18%) 4.7% 99 to 77 mg/dL (22%)
 HPS-DM 10 17.5 to 11.5% (34%) 6.0% 124 to 86 mg/dL (31%)
 CARDS 11.5 to 7.5% (35%) 4% 118 to 71 mg/dL (40%)
 ASCOT-DM 11.1 to 10.2% (8%) 0.9% 125 to 82 mg/dL (34%)
 ASPEN 10 9.8 to 7.9% (19%) 1.9% 114 to 80 mg/dL (30%)
10: Primary prevention data 20: Secondary prevention
2○
1○

The differential benefit of LDLc lowering in patients with diabetes has
been evident from the earliest statin trials and is more evidence that
higher risk=greater benefit : 4S study: Major Coronary Events
1 2 3 4 5 6
100
90
80
60
50
0
55%
0
Diabetic – simvastatin
Diabetic – placebo
Nondiabetic – simvastatin
Nondiabetic - placebo
Diabetic - simvastatin
Diabetic - placebo
Risk reduction
p=0.002
Coronary Death and non-fatal MI
Years since randomization
Pyörälä K, et al. Diabetes Care. 1997;20:614–620
Percent of patients without
major CV event
70

Within a given population, lower goals do further reduce CVD
events: Risk Curve Concept
Higher risk patients have more to gain from aggressive therapy
CHD + Diabetes
CHD + MS or IFG
CHD - NoMS or IFG
Diabetes - No CVD
Robinson JG, Stone NJ. Am J Cardiol. 2006;98:1405-1408
0
Cardiovascular Event Rate (%)
0 20 40 60 80 100 120 140 160 180 200
LDL (mg/dL)
No CVD - No diabetes
80
70
60
50
40
30
20
10

What aggressive LDL lowering does: reduces atheroma
volume in arterial wall providing plaque ‘stabilization’
Treated: LDLc of 84 mg/dL (47%
reduction)
Untreated: LDLc of 163 mg/dL with
statin+resin
Brown et al. Arter Thromb Vasc Biol 2001;21:1623

LDLc lowering and residual risk – more is needed
The majority of CVD events still occur: CVD events occurring in the on-treatment
100
90
80
70
60
50
40
30
20
10
0
4S LIPID CARE HPS WOS AFCAPS
N 4,444 9,014 4,159 20,536 6,595 6,605
ΔLDL -36% -25% -28% -29% -26% -27%
TxLDL 119 154 98 90 113 112
secondary high risk primary
%
CHD
events
on
statin
J Am Coll Card 2005;46:1225-8
groups in major statin trials

Despite the need beyond LDLc lowering, outcomes
data supporting combination therapy still limited
ADA Standards of Care; Diabetes Care, January 2011

The lipid arm of the ACCORD trial was relatively disappointing for
combination therapy (as was FIELD in 2005)– WHY?
April 29, 2010 N Engl J Med
Conclusion: “The combination of fenofibrate and simvatatin did not reduce the rate of
fatal cardiovascular events, non-fatal MI or non-fatal stroke, as compared with
simvatatin alone.”

ACCORD
LIPID: Lipid
parameters

Statins are safe but nothing is without risk: Review of 35
statin therapy trials
FDA-approved statin* monotherapy vs placebo (N = 74,102)
KashaniA et al. Circulation. 2006;114:2788-97.
Outcome
Statin
(%)
Placebo
(%) RD P value
Myalgias 15.4 18.7 2.7 0.37
CK elevations 0.9 0.4 0.2 0.64
Rhabdomyolysis 0.2 0.1 0.4 0.13
LFT elevation 1.4 1.1 4.2 <0.01
AE discontinuation 5.6 6.1 -0.5 0.80
*Atorvastatin, fluvastatin, lovastatin, pravastatin,
rosuvastatin, simvastatin
CK = creatine kinase
AE = adverse events
Statin better Placebo better
-30 -15 0 15 30
Risk difference per 1000 patients (RD)
(95% CI)

Hypertension
 Diabetes along with Hypertension increases risk of CVD by 5
times.
 Assosciation of SBP with macroand microvascular
complications – UKPDS 36
 Treatment of HTN has beneficial aspects with respect to
diabetes
 SHEP trial – Chlorthalidone
 HOPE trial – Ramipril
 Aggressive BP control has protective effect on CV mortality –
HOT,UKPDS.
 Aggressive BP control > aggressive glucose control -UKPDS.

Historic goal SBP of < 130 mmHg in diabetes is an
extrapolation of data regarding benefits in nephropathy
AJKD 2004;43(suppl 1):S120

Haven’t previous trials found a benefit from tighter BP control in diabetes?
…ended up comparing mean of 154/87 to 144/82

Four trials looked at major CVD outcomes based on randomized BP control;
Two trials (ABCD) were exclusively in patients with diabetes
Cochrane review 2009

April 29th, 2010 N Engl J
Med

ACCORD BP: Results
Conclusions: “In patients with type 2 diabetes at high risk for cardiovascular
events, targeting a systolic blood pressure of less than 120 mmHg, as compared
with less than 140 mmHg, did not reduce the rate of fatal and nonfatal major CVD
events.”

ACCORD BP: Using an average of 3 drugs, the authors
achieved a SBP of 119 mmHg vs. 133 mmHg

Implications on practice
 Summary of the evidence:
 Lower BP goals
Trial Goal (mmHg) Achieved (mmHg)
ABCD (H) DBP 75 vs 80-89 132/78 vs 138/86
ABCD (N) DBP 10 < baseline vs 80-89 128/75 vs 137/81
ACCORD SBP <120 vs <140 119/64 vs 133/70
 Lower BP goals:
 Do not change overall CV outcomes (all 3 trials).
 Do reduce rates of stroke (ABCD (H) and ACCORD, but how clinically sig?).
 Do help to reduce the progression of nephropathy in terms of urinary albumin
excretion and progression of microalbuminuria to overt albuminuria (ABCD (H)
and (N)).

Management of diabetes
 Oral hypoglycemic agents –
Metformin,Sulfonylureas,Glitazones,Incretin based
therapies.
 Insulin
 Insulin analogues

complications
 Poor wound healing
 Aneurysms
 Instent restenosis
 Aspirin intolerance

Precautions
 Adequate control of blood sugars
 S creatinine
 Adequate hydration
 Compliance with drugs – on day of procedure also

Perioperativemanagement
 CAD + Cardiovascular autonomic dysfunction + anaesthesia + surgical
stress + postoperative pain ---------- PERIOPERATIVE RISK
 Modified Goldman risk index .
 Five independent preoperative clinical predictors of postoperative
myocardial ischemia – HTN,LVH on ECG,diabetes mellitus on
Rx,documented CAD,digoxin use.
 Risk of postoperative myocardial ischemia - 22% without any
predictors,31% - one,46% with two ,77% with four predictors.
 Revised cardiac index

Prevention
 Primordial
 Primary
 Secondary
 Rehabilitation
 Primordial – lifestyle changes,healthy diet,exercise.
 Primary - Aspirin ? ,metformin (Met Synd),Statins
 Secondary – Aspirin,ACEI/ARBS,CCBs,Statins

ASA: The benefit of anti-platelet therapy is greater in higher risk patients and quite
low in low risk patients
Carlo Patrono, Barry Coller, Garret A. FitzGerald, Jack Hirsh, and Gerald Roth
CHEST 2004;126: 234S-264S.
2 Events prevented per
1000 treated in healthy
population

While the benefit of aspirin increases as risk increases, bleeding stays constant
Risk vs. benefit in primary vs. secondary prevention with ASA
So the benefits of antiplatelet therapy in low-risk patients is offset by major
bleeding episodes:
NEJM 2005;353:2373-83

Nine trial meta-analysis in
ADA/AHA/ACCF statement:
CHD: RR 0.91 (0.79-1.05)
Stroke: RR 0.85 (0.66-1.11)

What about bleeding in patients with diabetes?
Generic estimate ~ 1/1000 per year for non-stroke bleeding and ~
1/10,000 for hemorrhagic stroke
In patient-level ATT meta-analysis, patients with diabetes examined
separately: 25 GI bleeds with ASA (0.23%) and 22 bleeds with placebo
(0.21%)
Hemorrhagic stroke: 6 events on ASA, 9 on placebo
The Bottom Line
At a 10% 10-year risk of MI and Stroke, aspirin would prevent 1 MI and 1 stroke
and maybe cause 1 major GI bleed. At a 20% 10-year risk, 2 MIs and 2 strokes
would be prevented with no change in bleed risk

ADA Standards of Care, Diabetes Care; January, 2011

We have known for decades that platelets are more “responsive” in
patients with diabetes. Reasons are still not fully understood nor
the impact on use of anti-platelet agents

Take home message
 Diabetes is an ongoing epidemic.
 Diabetes increases risk for virtually all CVD complications and most
notably atherosclerotic vascular disease and HF.
 Gap between the accumulated evidence and its application clinically in
patients with diabetes to be addressed.
 Unraveling the diabetes –CVD conundrum and reversing the current
trend of expanding diabetes and assoaciated complications require
renewed commitments on the parts of patients,doctors,health care
institutions with primary focus on prevention.

WORLD DIABETES DAY
November 14,every year
An International Diabetes Federation initiative
for creating Global awareness on Diabetes.
In memory of Frederick Banting’s birthday
.

Theme for 2014 -2016
Healthy Living
&
Diabetes
Lets Unite for
Diabetes

DIABETES AND CARDIOVASCULAR DISEASE - THE CONTINUUM

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to DIABETES AND CARDIOVASCULAR DISEASE - THE CONTINUUM

Similar to DIABETES AND CARDIOVASCULAR DISEASE - THE CONTINUUM (20)

More from Praveen Nagula

More from Praveen Nagula (20)

Recently uploaded

Recently uploaded (20)

DIABETES AND CARDIOVASCULAR DISEASE - THE CONTINUUM