Vascular Complications

of Diabetes
Are they Preventable???
13th October, 2009

Arab Health Congress

Abu Dhabi, UAE

BY

Dr. Richard Nabhan

Consultant Physician, Cardiologist & Diabetologist
Fellow of the Royal Collage of Physicians (London)

Presentation outline (Macrovascular Complications)

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Presentation outline (Microvascular Complications)

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Presentation
outline
(Prevention)
PRESENTATION
OUTLINE
(Prevention)
Can we
prevent those
dreadful
complication ?

Why?

How?

MACROVASCULAR COMPLICATIONS

THE WEAPON

PATHOPHYSIOLOGY of Atherosclerosis
Atherosclerosis is the leading cause of death & disability in
the world
Key processes in atherosclerosis are the intimal thickening
& lipid accumulation that produce the characteristic
atheromatous plaques
Atherosclerosis is a slow & progressive disease that often
begins as early as infancy

ATHEROSCLEROSIS & PLAQUE FORMATION

CONSEQUENCES OF ATHEROSCLEROTIC LESIONS

Myocardial infraction (MI)
Cerebrovascular accident
Aortic aneurysm
Sudden cardiac death
Chronic ischemic heart disease
Ischemic encephalopathy
Gangrene of the legs
Mesenteric occlusion
9

MACROVASCULAR COMPLICATIONS

CARDIAC COMPLICATIONS

10

CHARACTER OF THE ISCHEMIC CHEST PAIN

Vice like

Constricting pain

Crushing weight or pressure

ACUTE COMPLICATIONS ASSOCIATED WITH HEART ATTACK

Heart Attack with
shock-collapse

Heart Attack
+
Acute heart failure
+
Shock
)Very High death rate (

Acute drop in BP

Heart Attack
Acute
heart
failureSOB
followed
by chest
pain. 11
Chest Pain

Ischemic Chest Pain is Triggered By Effort

and Relieved by Rest
Supply
Demand

Narrowed artery cannot

Loss of balance between

supply blood during effort

demand and supply

12

ACUTE CORONARY SYNDROMES

1. Unstable Angina
2. Non STEMI
3. STEMI

OPENING THE ACUTE OCCLUSION BY THROMBOLYTICS

Dissolving a fresh clot before organizing to open the occlusion.
This has to be done within 12 hours.
This group of drugs have their indications and contraindications.
Special circumstances govern its use like Streptokinase , Urokinase, & tPA.

REVASCULARISATION OF OCCLUSIONS BY PCI OR CABG

Coronary angiogram

Ballooning

Stenting

Before

After

Coronary bypass

Before

After

14

MACROVASCULAR COMPLICATIONS

CEREBROVASCULAR COMPLICATIONS

15

16

HEMORRHAGIC

ISCHEMIC

STENOSIS OR OCCLUSION OF CAROTID ARTERY

17

ISCHEMIA OF INTERNAL CAROTID ARTERY

TERRITORY

18

ISCHEMIA OF VERTEBROBASILAR TERRITORY

19

CARDIAC SOURCES OF CEREBRAL EMBOLI

20

MACROVASCULAR COMPLICATIONS

PERIPHERAL ARTERY DISEASE (PAD)

21

NATURAL HISTORY OF PAD

Initial Clinical Presentation

Asymptomatic
20% to 50%

Atypical leg pain

40% to 50%

Critical leg ischemia*

1% to 2%

Intermittent claudication
10% to 35%

5-Year Outcomes
Cardiovascular
Disease

Limb Morbidity
Stable

Worsening

Critical limb ischemia

1% to 2%

1-Year Outcomes
Alive, no amputation, 50%

Amputation, 25%

Nonfatal
20%

Fatal
15% to 30%

Cardiovascular causes, 75%

Death, 25%

*Chronic ischemic rest pain, ulcers, or gangrene attributable to atherosclerotic occlusive disease.
PAD = peripheral arterial disease.

22

RISK FACTORS FOR PAD

Risk factors for lower extremity PAD, showing range of
RR estimated from epidemiologic studies
Smoking
Diabetes
Hypertension
Hypercholesterolemia
Hyperhomocysteinemia
C-reactive protein (CRP)
.5

5
23

PATHOPHYSIOLOGY OF PAD
Atherosclerotic disease process
becomes symptomatic when
occlusive lesions cause limb
ischemia
In patients with IC, limb blood
flow may be normal during rest
but markedly inadequate during
exercise
In time, ischemia can cause
neurologic and metabolic
changes in skeletal muscle that
lead to functional impairment of In this angiogram, the right
common iliac artery exhibits
the affected limb

a high-grade stenosis, and a

mild stenosis
24 can be seen in
the left common iliac artery.

INTERMITTENT CLAUDICATION
A subset of patients with symptomatic PAD
Leg pain
Produced by exercise
Relieved by rest
Caused by arterial occlusive disease
Dependent on location and extent of occlusion
Leading to deconditioning of muscle
Resulting avoidance of activity leads to
deconditioning of muscle

25

CRITICAL LIMB ISCHEMIA (CLI)

The usual presenting symptom is ischemic pain at rest; patients
may also present with ulceration or gangrene
Risk factors that reduce blood flow
Diabetes
Renal failure
Severely decreased cardiac output
Smoking
Vasospastic disease
Risk factors that increase blood-flow demand
Infection
Skin breakdown or traumatic injury
26

Retinopathy
Proved Evidences

Diabetic Retinopathy is the major cause of visual

blindness in the world.
Diabetes in sole causes blindness in 33% of type
2 diabetes patients.
Increased risk of cataracts in diabetics.
High diastolic BP is a risk factor for macular
Edema.

MICROVASCULAR COMPLICATIONS

R ETINOPATHY

Micro aneurysms

Cercinate Hard Exudates

Dot Hemorrhages

Intraretinal MicroVascular
Abnormalities

Soft Cotton Wool Exudates

Venous Beading

Retinal Ischemia

NVEs

Occluded Vessel

NVD

NVE

NVD

NVD

Subhyaloid Hemorrhages

NVE

Exudative maculopathy

Subhyaloid Hemorrhages

Exudative maculopathy

Exudative Maculopathy

Gliosis of Vessels

Ischemic Retinopathy

Photo Coagulation

Preretinal Hemorrhage Tractional Detachment

Diabetic Retinopathy: A Progressive Disease

Diabetic
Macular
Edema

Proliferative
Diabetic
Retinopathy

Nonproliferative
Diabetic
Retinopathy

Preclinical

None, or blurred
vision

Non, or reduced
vision or floaters

None, or blurred vision

& glare

None

Symptoms

Swelling of
retina due to
leaky capillaries
Increased
capillary leakage
Fluid
accumulation in
retinal layers

Retinal
vasodilatation
Beading
IRMAs
Neovascularization or optic
disc, retina, &/ or
iris

Retinal vasodilatation
Microaneurysms
Nerve fiber layer
infarcts
Intraretinal
hemorrhages
IRMAs
Venous bleeding

Normal
appearing
retina

Clinical
signs
indicating
need for
referral

32

Staging of Diabetic Retinopathy

Observable (Dilated
Ophthalmoscope)

Disease Severity Level

No abnormalities

No apparent retinopathy

Microaneurysm only

Mild Non-Proliferative Diabetic Retinopathy

More that just microaneurysms but less

than severe nonproliferative diabetic
retinopathy

Moderate Non-Proliferative Diabetic

Retinopathy

Any of the following:

More than 20 intraretinal hemorrhages in
each of 4 quadrants
Definitive venous beading in 2+
quadrants
Prominent IRMA in 1+ quadrant & no
signs of proliferative diabetic retinopathy

Severe Non-Proliferative Diabetic

Retinopathy

One or more of the following:

Neovascularization
Vitreous/ peretinal hemorrhage

Proliferative Diabetic Retinopathy

33

Staging of Diabetes Macular Edema

Observable (Dilated
Ophthalmoscope)

Disease Severity Level

No retinal thickening or hard exudates in

posterior pole

No diabetic macular edema present

Mild Diabetic Macular Edema

Some retinal thickening or hard exudates
in posterior pole but distant from the
center of the macula

Moderate Diabetic Macular Edema

Retinal thickening or hard exudates
approaching the center of the macula but
not involving the center

Diabetic macular edema present

Sever Diabetic Macular Edema

Retinal thickening or hard exudates
involving the center of the macula
34

Clinical Guidelines for Early Detection of Diabetic

Retinopathy & Diabetic Macular Edema
Minimum routine
follow-up +

Recommended first
examination *

Yearly

Within 3-5 years after

Type 1 diabetes
diagnosis once patient
is age 10 years or older

Yearly

At time of diagnosis of
diabetes

Type 2 diabetes

Physician discretion
pending results of first
trimester exam

Priority to conception
& during first trimester

Pregnancy in preexisting diabetes

Patient group

Eye exam should be performed through dialed pupils by qualified eye specialist

+ Abnormal findings necessitate more frequent follow-up

35

MICROVASCULAR COMPLICATIONS

DIABETIC NEPHROPATHY

Natural History of Diabetic Nephropathy

DEATH

37

38

38

Five Stages of Kidney Disease

STAGE 1: Hyperfiltration, or an increase in glomerular
filtration rate (GFR) occurs. Kidneys increase in size.
STAGE 2: Glomeruli begin to show damage and
microalbuminurea occurs.
STAGE 3: Albumin excretion rate (AER) exceeds 200
micrograms/minute, and blood levels of creatinine and
urea-nitrogen rise. Blood pressure may rise during this
stage.
STAGE 4: GFR decreases to less than 75 ml/min, large amounts of protein pass
into the urine, and high blood pressure almost always occurs. Levels of creatinine
and urea-nitrogen in the blood rise further.
STAGE 5: Kidney failure, or end stage renal disease (ESRD). GFR is less than 10
ml/min. The average length of time to progress from Stage 1 to Stage 4 kidney
disease is 17 years for a person with type 1 diabetes. The average length of time
to progress to Stage 5, kidney failure, is 23 years.
39

Clinical Guidelines for Early Detection of Diabetic

Nephropathy
Test

When

Normal Range

Blood
pressure

Each office visit

< 130/80 mm Hg

Urinary
albumin

Type 2: Annually
beginning at
diagnosis

< 13 g/mg creatinine

(random spot collection)
Equivalent to:

Type 1: Annually, 5
years post-diagnosis

< 30 mg/day unirary albumin excretion

< 20 g/min urinary albumin excretion (timed
specimen)

40

Can We Prevent Diabetic Nephropathy?

Maintain BP <130/80 mm/Hg

Maintain FBG <100 mg/dl
Maintain PPG <140 mg/dl
Maintain A1C <6.0%
Maintain BP < 120/75 in case of Microalbuminurea

41

MICROVASCULAR COMPLICATIONS

DIABETIC NEUROPATHY

42

Symptoms & Signs of Diabetic Peripheral

Neuropathy

43

Diabetic Peripheral Neuropathy Severity Scale

Rating

Description

No neuropathy

Subclinical diabetic peripheral neuropathy

2a

Clinical diabetic peripheral neuropathy with

symptoms, mild to moderate

2b

Clinical diabetic peripheral neuropathy insensate

foot, loss of feeling/ negative symptoms

Disability/ late stage

44

Diabetic Peripheral Neuropathy

Can Progress Over Time
Symptoms may occur any
time and intermittently
Patients may or may not
have symptoms of diabetic
peripheral neuropathy
Patients frequently do not
report symptoms to their
physicians until the
symptoms are severe
The majority of signs of
diabetic peripheral
neuropathy are not evident
at the onset of diabetes
45

Clinical Guidelines for Early Detection of Diabetic

Peripheral Neuropathy
Stages

Characteristics

Stages 0/1:
No clinical neuropathy

No symptoms or signs

Stage 2a:
Clinical neuropathy

Positive symptomology (increasing pains at night),

burning, stabbing pains, pains & needles; absent
sensation to several modalities & reduced or absent
reflexes
Less common-diabetes poorly controlled, weight loss,
diffuse (trunk), minor sensory signs

Stage 2b:
Clinical neuropathy

No symptoms or numbness of feet, reduced thermal

sensitivity, painless injury

Stage 3:
Disability/ late stage

Foot lesions (eg, ulcers), neuropathic deformity (eg,

Charcot joint), non-traumatic amputation
46

Clinical Guidelines for Management of Diabetic

Peripheral Neuropathy
Stages

Objectives

Referral

Stages 0/1:
No clinical
neuropathy

Education to reduce risk of

progression, glycemic control,
annual assessment

As required

Stage 2a:
Clinical
neuropathy

Stable glycemic control,

symptomatic treatment,

Diabetologist,
neurologist

Stage 2b:
Clinical
neuropathy

Education, especially foot care,

glycemic control according to needs

Foot care team

Stage 3:
Disability/ late
stage

Prevention or new/ recurrent lesions

& ampulation, emergency referral if
lesions present, otherwise referral
within 4 weeks

Diabetologist,
neurologist,
chiropodist,
podiatrist, diabetes
specialist nurse,
diabetic foot clinic
if available
47

Genitourinary Autonomic Neuropathy

Sign/ Symptom

Treatment

Bladder dysfunction

Voluntary urination, catheterization

Retrograde ejaculation

Antihistamine

Erectile dysfunction

Slidenafil, tadalafil

Dyspareunia

Lubricants, estrogen creams

48

Gastrointestinal Autonomic Neuropathy

SYMPTOMS/SIGNS
Gastroparesis resulting in anorexia, nausea,
vomiting, and early satiety
Diabetic enteropathy resulting in diarrhea and
constipation
TREATMENT
Other causes of gastroparesis or enteropathy
should first be ruled out
Gastroparesis - Small, frequent meals,
metoclopramide, erythromycin
Enteropathy - loperamide, antibiotics, stool
softeners or dietary fiber
49

Cardiovascular Autonomic Neuropathy

SYMPTOMS / SIGNS
Exercise intolerance
Postural hypotension
Silent Ischemia
TREATMENT
Discontinue aggravating drugs
Change posture (make postural changes slowly,
elevate bed)
Increase plasma volume
50

MICROVASCULAR COMPLICATIONS

DIABETIC FOOT

51

Examination of PAD in Diabetic Foot :

52

Vascular Complications of PAD

(in Diabetic Foot)

53

54

Deformities

Motor Neuropathy

Autonomic Neuropathy

Pedography

55

56

Parasthesia inspite of
lack of Sensation

Sensory Neuropathy

Ulsers of the Foot

Candidates for Amputation

57

58

Late detection because

of lack of Sensation

Portals of infection

Fungus of the Nails

59

COMPONENTS OF SECONDARY PREVENTION

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

Cigarette smoking cessation

Blood pressure control
Lipid management to goal
Physical activity
Weight management to goal
Diabetes management to goal
Antiplatelet agents / anticoagulants
Renin angiotensin aldosterone system blockers
Beta blockers
Influenza vaccination
60

CIGARETTE SMOKING RECOMMENDATIONS

GOAL: Complete Cessation and No Exposure

to Environmental Tobacco Smoke
1.

Ask about tobacco use status at every visit.

2.

Advise every tobacco user to quit.

3.

Assess the tobacco users willingness to quit.

4.

Assist by counseling and developing a plan for

quitting.

Arrange follow-up, referral to special

5.

programs,
or pharmacotherapy (including nicotine replacement
& bupropion.

6.

Urge avoidance of exposure to environmental

tobacco smoke at work and home.
61

SECONDARY PREVENTION OF CVD

BLOOD PRESSURE CONTROL

62

BLOOD PRESSURE CONTROL

RECOMMENDATIONS
GOAL <140/90 mm Hg
<130/80 if DM or CKD
Blood pressure 120/80 mm Hg or greater:
Initiate or maintain lifestyle modification: weight
control, increased physical activity, alcohol moderation,
sodium reduction, and increased consumption of fresh
fruits vegetables and low fat dairy products
Blood pressure 140/90 mm Hg or greater (or 130/80 or
greater for chronic kidney disease or diabetes)
As tolerated, add blood pressure medication, treating
initially with beta blockers and/or ACE inhibitors with
addition of other drugs such as thiazides as needed to
achieve goal blood pressure
63

JNC VII Lifestyle Modifications for BP Control

Modification

Recommendation

Approximate SBP
Reduction Range

Weight reduction

Maintain normal body weight

(BMI=18.5-24.9)

5-20 mmHg/10 kg
weight lost

Diet rich in fruits, vegetables, low

fat dairy and reduced in fat

8-14 mmHg

Restrict sodium
intake

<2.4 grams of sodium per day

2-8 mmHg

Physical activity

Regular aerobic exercise for at

least 30 minutes on most days of
the week

4-9 mmHg

<2 drinks/day for men and <1

drink/day for women

2-4 mmHg

Adopt DASH
eating plan

Moderate
alcohol
consumption

BMI=Body mass index, SBP=Systolic blood pressure

64

THE RISK OF DYSLIPIDEMIA

65

Lipid Parameter Function:

Latest Commentary

VLDL
Carries triglycerides to peripheral cells
High levels may be associated with increased CHD risk
LDL
Carries cholesterol to cells
High levels linked to increased CHD risk
Primary target of cholesterol-reducing therapy
HDL
Removes cholesterol from cells
High HDL considered protective against CHD
HDL >60 mg/dL decreases CHD risk
Lipoprotein(a)
A complex of LDL and apolipoprotein(a)
Prevents LDL from being taken up by the Liver
Elevated Lp(a) is an independent risk factor for premature CHD
Triglycerides
A neutral fat stored in adipose cells
Positively correlated with risk for CHD
66

New Lab Technology

Berkeley Heart Lab & Lipoprofile
LDL sub-classes- small dense (IIIa & IIIb) vs
large buoyant
HDL sub-classes- HDL2b
Lp(a)
Homocysteine
Insulin
C-reactive protein

67

Current Treatment Methods

1. Exercise & Diet
a. Poor compliance
b. Usually cannot get to target levels

2. Statins
a. Great at lowering LDL levels
b. Not much affect on Lipoprotein(a), HDL,
or small dense LDL, and minor effects
on
Triglycerides
68

The Uniqueness of Niacin

Increases HDL better than ANY other

medication and increases HDL2b the
most
Only drug that has been shown to
switch subclasses of LDL from small
dense (IIIa and IIIb), to large buoyant
(Pattern B to Pattern A)
Decreases Lp (a) the best of any
medication
69

PHYSICAL ACTIVITY RECOMMENDATIONS

GOAL: 30 minutes (7) days/week,
minimum (5) days/week
Assess risk with a physical activity history
and/or an exercise test, to guide prescription
Encourage 30 to 60 minutes of moderate
intensity aerobic activity such as brisk
walking, on most, preferably all, days of the
week, supplemented by an increase in daily
lifestyle activities
Advise medically supervised programs for
high-risk patients (e.g. recent acute coronary
syndrome or revascularization, HF)
70

WEIGHT MANAGEMENT RECOMMENDATIONS

GOAL: BMI 18.5 to 24.9 kg/m2
Waist Circumference: Men: < 40 inches
Women:
< 35 inches

Assess BMI and/or waist circumference on each visit &

consistently encourage weight maintenance/ reduction
through an appropriate balance of physical activity, caloric
intake, and formal behavioral programs when indicated.

If waist circumference (measured at the iliac crest) >35

inches in women and >40 inches in men initiate lifestyle
changes and consider treatment strategies for metabolic
syndrome as indicated.
The initial goal of weight loss therapy should be to reduce
body weight by approximately 10 percent from baseline. With
success, further weight loss can be attempted if indicated.

71
*BMI is calculated as the weight in kilograms divided by the body surface area in meters 2.
Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2.

71

DIABETES MELLITUS RECOMMENDATIONS

GOAL: Hb A1c < 6%
Lifestyle and pharmacotherapy to achieve near
normal HbA1C (< 6%)
Vigorous modification of other risk factors (e.g.,
physical activity, weight management, blood
pressure control, and cholesterol management as
recommended)
Coordinate diabetic care with patients primary
care physician or endocrinologist
HbA1c = Glycosylated hemoglobin
72

ANTICOAGULATION RECOMMENDATIONS

Manage warfarin to international normalized

ratio 2.0 to 3.0 for paroxysmal or chronic
atrial fibrillation or flutter, and in post-MI
patients when clinically indicated (e.g., atrial
fibrillation, LV thrombus.)
Use of warfarin in conjunction with aspirin
and/or clopidogrel is associated with
increased risk of bleeding and should be
monitored closely
73

ASPIRIN RECOMMENDATIONS
Start and continue indefinitely aspirin 75 to
162 mg/d in all patients unless
contraindicated
For patients undergoing CABG, aspirin (100 to
325 mg/d) should be started within 48 hours
after surgery to reduce saphenous vein graft
closure
Post-PCI-stented patients should receive 325
mg per day of aspirin for 1 month for bare
metal stent, 3 months for sirolimus-eluting
stent and 6 months for paclitaxel-eluting stent
74

CLOPIDOGREL RECOMMENDATIONS

Start and continue clopidogrel 75 mg/d in

combination with aspirin

for post ACS or post PCI with stent

placement patients for up to 12 months

for post PCI-stented patients

>1 month for bare metal stent,
>3 months for sirolimus-eluting stent
>6 months for paclitaxel-eluting stent

*Clopidogrel is generally given preference over Ticlopidine because

of a superior safety profile
75

ACE INHIBITOR RECOMMENDATIONS

Use in all patients with LVEF < 40%, and

those with diabetes or chronic kidney
disease indefinitely, unless
contraindicated
Consider for all other patients
Among lower risk patients with normal
LVEF where cardiovascular risk factors
are well controlled and where
revascularization has been performed,
their use may be considered optional
ACE= Angiotensin Converting Enzyme,
LVEF= Left Ventricular Ejection Fraction

76

ANGIOTENSIN RECEPTOR BLOCKER

RECOMMENDATIONS
Use in patients who are intolerant of ACE
inhibitors with HF or post MI with LVEF
less than or equal to 40%.
Consider in other patients who are ACE
inhibitor intolerant.
Consider use in combination with ACE
inhibitors in systolic dysfunction HF.
ACE= Angiotensin Converting Enzyme Inhibitor,
LVEF= Left Ventricular Ejection Fraction,
HF= Heart Failure, MI=Myocardial Infarction
77

LDOSTERONE ANTAGONIST RECOMMENDATION

Use in post MI patients, without significant

renal dysfunction or hyperkalemia, who
are already receiving therapeutic doses of
an ACE inhibitor and beta blocker, have an
LVEF < 40% and either diabetes or heart
failure
*Contraindications include abnormal renal function (creatinine >2.5 mg/dL in
men or >2.0 mg/dL in women) and hyperkalemia (K+ >5.0 meq/L)
ACE= Angiotensin Converting Enzyme Inhibitor,
LVEF= Left Ventricular Ejection Fraction,
MI=Myocardial Infarction

78

B-BLOCKER RECOMMENDATIONS

Start and continue indefinitely in all post

MI, ACS, LV dysfunction with or without
HF symptoms, unless contraindicated.
Consider chronic therapy for all other
patients with coronary or other vascular
disease or diabetes unless
contraindicated.
*Precautions but still indicated include mild to moderate asthma or chronic
obstructive pulmonary disease, insulin dependent diabetes mellitus, severe
peripheral arterial disease, and a PR interval >0.24 seconds.
MI= Myocardial infarction, HF= Heart Failure
79

INFLUENZA VACCINATION

Patients with cardiovascular disease should have influenza

vaccination
80

SECONDARY PREVENTION CONCLUSIONS

1. Evidence confirms that aggressive
comprehensive risk factor management
improves survival, reduces recurrent events
and the need for interventional procedures,
and improves the quality of life for these
patients.
2. Every effort should be made to ensure that
patients are treated with evidence-based,
guideline recommended, life-prolonging
therapies in the absence of contraindications
or intolerance.
81

For a Healthier
Beware
Community
the terrorists of
the Arteries
Diabetes

Hypertension
Cholesterol
Smoking

Obesity over weight

Lack of exercise
Unbalanced diet
Lack of awareness
Stress