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

First Manufacturer of Insulin.

Funded the Scientists

Insulin Syringe used for experiment by Best and Banting

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

3.Types of diabetes

4.Etiopathogenesis

5.Special points with regards to CVD

6.Evaluation of patient with diabetes for CVD

7.Management

8.Prevention

9.Take home message

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

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

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

Contents


2.Epidemiology

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

• Lack of insulin

• Autoimmune

• Usually children

Types of Diabetes

Type 1 diabetes Type 2 diabetes Gestational diabetes

• Insulin resistance

• Lifestyle factors

• Usually adults

• Insulin resistance

• During pregnancy

• Risks to mother and

child

Other specific types

Monogenic – MODY

LADA

Contents


2.Epidemiology

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

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 ?

Retnakaran R, Zinman B. Lancet 2008;371:1790-99.

Hyperglycemia is toxic at several steps in the atherosclerosis process

NEW ENGLAND JOURNAL OF MEDICINE March 4, 2010

Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Non-

diabetic AdultsElizabeth Selvin, Michael Steffes, Hong Zhu, Kunihiro Matusushita, et al.

There is a clear epidemiologic association between glycemic control and CVD

Data from 11,092 black and white

subjects in the ARIC trial

(Atherosclerosis Risk in

Communities)

Median follow approximately 14

years.

ADA position on glycemia

and macrovascular disease in

2010 Standards of Care

Guideline

ADA Standards of Care.

Diabetes Care 2010;33:S11-62

Despite clear epidemiology, controversy continues regarding the role

of glucose lowering to prevent coronary events

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

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.

So hyperglycemia doesn’t matter to the heart?

Non-fatal MI significantly reduced 24% (p=0.001)

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%

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.

So hyperglycemia matters to the heart but intense control (A1C < 7%) provides little additional

benefit over moderate control (A1C 7-8%)

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

14% decrease per 1% decrement in HbA1c

p<0.0001

0.5

1

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

InsulinResistance

Hypertension

Type 2 Diabetes

Disordered

Fibrinolysis

Complex

Dyslipidemia

TG, LDL

HDL

Endothelial

DysfunctionSystemic

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

Type 2 diabetes

Time

Insulin

resistance

Insulin

production

Glucose

level

b-cell

dysfunction

Endothelial 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 DiabeticsFramingham 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)

109

20

11

9 63819

3*

30

0

2

4

6

8

10

Age-adjusted annual rate/1,000

Men Women

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.

Contents

1.Definition

2.Epidemiology

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

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

Sleep apnea

CVD

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.

Diabetes in pregnancy

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.

Contents

1.Definition

2.Epidemiology

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

Evaluation of a patient with diabetes for CVD .

ECG

2D ECHO

TMT

Stress Echocardiography

CAG

PTCA - BMS/DES

CABG

Carotid stenting

Peripheral angioplasty

Exercise stress testing

Contents

1.Definition

2.Epidemiology

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

Management of comorbidities

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 processBasic 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

VLDL

T

G

IDL

LDL

Lipase

enzymes

Lipase

enzymes

LDLc

Type

(%)

Appearance of

serum

Elevated

particles

Associated clinical disorders TC

T

GI (~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 + ++

Fredrickson Classification of Dyslipidemia

We look at thisArtery wall sees these

LDL

LDL

Endothelium

Vessel LumenMonocyte

Macrophage

MCP-1

Adhesion

Molecules

Steinberg D et al. N Engl J Med 1989;320:915-924.

The primary atherogenic lipoprotein is LDLlipoproteins of > 70 nm have limited transcytosis past the endothelium

Foam Cell

Modified

LDL Taken

up by

Macrophage

Intima

Nascent

chylomicronNascent

VLDL

ΧΧ

Artery wall

Proatherogenic LDL

Am Heart J 2008;156:112-119

2. Dyslipidemia vs. Hyperlipdemia: Prevalence in NHANES 2008 data: High TG or low HDLc more

common than high LDLc

Prevalence of Dyslipidemia is high in Type 2 Diabetes

Jacobs MJ, et al. Diabetes Res Clin Pract. 2005;70:263-269.

Control of Lipids Patients With

Diabetes, %

Patients Without

Diabetes, %

P Value

LDL-C

> 100 mg/dL74.7 75.7 NS

HDL-C

< 40 mg/dL (men)

< 50 mg/dL (women)63.7 40.0 < .001

Triglycerides

> 150 mg/dL61.6 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.

Hepatic lipase

Fat Cells Liver

Kidney

Insulin

CETP

CE

VLDL HDL

Lipoprotein lipase

or hepatic lipase

Small, dense

LDLLDL

TG

ApoA-ITG

CE

FFA

‘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

CE, cholesteryl esters; FFA, free fatty acids; TG, triglycerides.

Ginsberg HN. J Clin Invest. 2000;106:453–458.

CETP

↑ TG

↑ ApoB

↓ HDLc

↔ LDLc

XInsulin

resistance

Liver

IDL

FFA

While LDLc is similar,

particle burden is heavier

LDL particle count vs. cholesterol contentTo carry the same amount of cholesterol, a larger number of particles are needed

if they are smaller

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

Small, dense: 25-30 nmLarge, buoyant: 30-35 nm

LDLc=115 mg/dl LDLc=115 mg/dl

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

0

50

60

80

90

100

55%

0

Diabetic – simvastatin

Diabetic – placebo

Nondiabetic – simvastatin

Nondiabetic - placebo

Diabetic - simvastatin

Diabetic - placebop=0.002

Risk reduction

Coronary Death and non-fatal MI

Years since randomization

Pyörälä K, et al. Diabetes Care. 1997;20:614–620

Per

cent

of

pat

ients

wit

hout

maj

or

CV

even

t

70

Within a given population, lower goals do further reduce CVD

events: Risk Curve ConceptHigher risk patients have more to gain from aggressive therapy

Robinson JG, Stone NJ. Am J Cardiol. 2006;98:1405-1408

0Car

dio

vas

cula

r E

ven

t R

ate

(%)

0 20 40 60 80 100 120 140 160 180 200

LDL (mg/dL)

No CVD - No diabetes

Diabetes - No CVD

CHD - NoMS or IFG

CHD + MS or IFG

CHD + Diabetes

80

70

60

50

40

30

20

10

What aggressive LDL lowering does: reduces atheroma

volume in arterial wall providing plaque ‘stabilization’

Brown et al. Arter Thromb Vasc Biol 2001;21:1623

Treated: LDLc of 84 mg/dL (47%

reduction)

Untreated: LDLc of 163 mg/dL with

statin+resin

0

10

20

30

40

50

60

70

80

90

100

4S LIPID CARE HPS WOS AFCAPS

N 4,444 9,014 4,159 20,536 6,595 6,605

∆LDL -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

LDLc lowering and residual risk – more is neededThe majority of CVD events still occur: CVD events occurring in the on-

treatment 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

Kashani A et al. Circulation. 2006;114:2788-97.

FDA-approved statin* monotherapy vs placebo (N = 74,102)

*Atorvastatin, fluvastatin, lovastatin, pravastatin,

rosuvastatin, simvastatin

CK = creatine kinase

AE = adverse events

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

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.

AJKD 2004;43(suppl 1):S120

Historic goal SBP of < 130 mmHg in diabetes is an

extrapolation of data regarding benefits in nephropathy

Haven’t previous trials found a benefit from tighter BP control in diabetes?

…ended up comparing mean of 154/87 to 144/82

Cochrane review 2009

Four trials looked at major CVD outcomes based on randomized BP control;

Two trials (ABCD) were exclusively in patients with diabetes

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

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)).

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

Exercise prescribing

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

Perioperative management

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

Contents

1.Definition

2.Epidemiology

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

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 patientsCarlo 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

Risk vs. benefit in primary vs. secondary prevention with ASAWhile the benefit of aspirin increases as risk increases, bleeding stays constant

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

Contents

1.Definition

2.Epidemiology

3.Types of diabetes

4.Etiopathogenesis

5.Special points


7.Management

8.Prevention

9.Take home message

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

Thank You

DIABETES AND CARDIOVASCULAR DISEASE - THE CONTINUUM

Education

Transcript of DIABETES AND CARDIOVASCULAR DISEASE - THE CONTINUUM