Module 8

Macroangiopathy
 Objective

• To enumerate the micro-vascular complications of diabetes mellitus and

discuss their pathogenesis.
• To discuss on management of hypertension and dyslipidemia in a diabetic
person.
• To perform clinical examination of foot to detect “high risk foot” and advise
diabetics for appropriate foot care practice.
 Introduction to macro-vascular complications
of diabetes mellitus
• Diabetes mellitus is a disease associated with several macro-vascular complications
in the heart, brain and periphery (lower limb). The pathology that sets in such
complications are called Microangiopathy. According to site of involvement there
are three types of macroangiopathies.
 Introduction to macro-vascular complications
of diabetes mellitus
• Coronary artery disease (CAD)-in the heart
• Cerebrovascular disease (CVD) – in the brain
• Peripheral vascular disease (PVD) – in the lower limb

• Coronary artery disease is • Stoke (cerebrovascular disease) • Peripheral vascular disease

the commonest cause of is the second most common affecting the large arteries
death in persons with macro-vascular problem in particularly of the lower limbs
diabetes. Both of the above are are also common in diabetes.
diabetes. also important causes of • It adds considerably to the
premature mortality in morbidity related to foot
diabetes problems leading to lower
extremity amputations

CAD CVD PVD

Macro-vascular Complications
 Factors affecting Macroangiopathy
1. Duration of diabetes: Like microangiopathy, macroangiopathies of diabetes also increases
with duration of diabetes. T2DM people often present with macroangiopathy.
2. Status of glycemic control (blood glucose or HbA1c): strongly related to both micro and
macroangiopathies of diabetes.
3. Other factors
 Hypertension and dyslipidemia are the two very important modifiable factors in the
development of macroangiopathies.
 Smoking, obesity and lack of exercise are risk factors for Coronary Artery diseases.
 Genetic susceptibility to certain complications may be present.
 Age may be related to some complications.
 Insulin resistance is an indipendent risk factor.

All these factors should be taken into account during prevention and treatment of complications.
 Mechanism of macroangiopathy

 Atherosclerosis is the fundamental mechanism in development of macro vascular disease.

 The blood vessels become thick, hard and less elastic. This makes it difficult for the blood to
flow through.
 People with diabetes have atherogenic dyslipidemia.
 High blood glucose affects the RBCs and makes them less pliable and may produce
hypoxemia.
 There is increase in the factors that favour blood clotting, damage and change in vascular
endothelial lining, increased platelet stickiness etc.
 Atherosclerosis is several-fold more frequent in persons with diabetes. In diabetic people
atheromatuos lesions are more severe and widespread.
 Insulin resistance probably plays an important role.
Micro-vascular complications/ Diabetic micro-angiopathy: proposed mechanisms ( by Hyperglycamia)
 Atherosclerosis
is the fundamental lesion of macroangiopathy
[Findings during histopathology]

a. Tear in the arterial wall;

b. Macrophage cells;
c. Cholesterol deposit;
d. Red Blood Cells;
e. Macrophage Foam cells;
f. Fat cells
 Hypertension and DM
High blood pressure causes damage to large and small blood vessels in the body.
The higher the blood pressure the greater is the risk.
The adverse effect of hypertension mainly involves the blood vessels of heart, brain, eyes and kidneys.

Hypertension contributes to Depending on the severity of Hypertension may cause

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the development and hypertension, the optic fundi proteinuria and progressive
progression of chronic reveal a series of changes renal failure by damaging the
complications of diabetes. (hypertensive retinopathy). renal vasculature.
In patients with type1 Hypertension is also Diabetics are already at risk
diabetes, persistent associated with central of kidney disease and added
hypertension is often a retinal vein thrombosis. hypertension increases the
manifestation of diabetic Hypertension accelerates the risk of kidney disease several
nephropathy. progression as well as folds.
In type2 diabetes, increases the severity of
hypertension is often a part existing diabetic retinopathy.
of metabolic syndrome.
Organ affected by macroangiopathy
• LVH, • Stroke,
• MI, • TIA
• angina,
• heart failure

Heart Brain

Kidney
Limb
Eye
• CKD • PVD
• Retinopathy
 Target of blood pressure in diabetics
Many prospective studies with hypertensive diabetic persons have documented that reduction of
blood pressure is the single most important factor that reduces both renal disease progression and
cardiovascular events.
On the basis of those evidences now it is advised to lower the blood pressure to <140/80 mmHg, in
patients with diabetes, chronic kidney disease or target organ damage due to hypertension.

Target of blood pressure (based on ADA guideline)

In diabetes mellitus <140/90 mm of Hg
In CKD or TOD <140/90 mm of Hg
In general population <140/90 mm of Hg
BP <130/80 mmHg may be appropriate in certain individuals, e.g. young
patients.
 Treatment of hypertension in diabetes
Blood pressure should be measured at the initial visit and subsequently at every follow-up visit.
At initiation of therapy usually a single drug is used but if B.P > 160/100 mmHg two drug regimen
may be considered.
Follow-up monthly or more frequently to adjust medications; then at every follow-up visit.
Drug Therapy:
 Antihypertensive regimens should include ACE inhibitors (ACEI) or angiotensin II receptor
blockers (ARB) in order to provide maximum cardio- and renoprotection in these patients.
But these two must not be combined.
 In virtually all patients with diabetes, combination of antihypertensive medications may be
needed to achieve the desired blood pressure target.
 At least one drug is to be given at bed-time.
 Treatment of hypertension in diabetes
 Glycemic and lipid control must be ensured.
Non-pharmacological interventions
 Weight loss for obese
 Regular exercise
 Medical nutrition therapy-plenty of vegetables and fruits, reduced total and saturated fat
 Restriction of salt intake (<6 g/day)
 Limitation alcohol
Antihypertensive drugs
Antihypertensive drugs
 Dyslipidemia

• Dyslipidemia is defined as an abnormal level of one or more blood lipids-total

cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and/ or
triglyceride (TG). There is strong evidence that elevated LDL and decreased HDL levels
directly contribute to the formation of atherosclerotic plaques and in turn increase the
patient’s risk of cardiovascular disease.
• Though the concentration of total and LDL cholesterol in type2 diabetic patients is
usually not significantly different from non-diabetic individuals, the diabetics may have
elevated levels of non-HDL cholesterol (LDL and VLDL). However, type2 diabetic
patients typically have a preponderance of small and dense LDL particles, which
possibly increase atherogenicity even if the absolute concentration of cholesterol is not
significantly increased
 Dyslipidemia
Key features of diabetic dyslipidemia
 Hypertriglyceridemia
 A reduction in high-density lipoprotein cholesterol (HDL)
 A rise in small dense low-density lipoprotein cholesterol (LDL)

Cholesterol is an essential element of all animal cell membranes and forms the backbone of steroid
1. Cholesterol hormones and bile acides. Although dietary cholesterol found in foods of animal origin contributes to the
plasma cholesterol level, endogenous production is believed to account for most plasma cholesterol.
Triglycerides are simple lipids derived from fatty acids. Vegetable oils, dairy products and animal fast contain
2. Triglycerides triglycerides. VLDL, a precursor of LDL, is involved in the transportation of endogenous triglyceride from the liver
to the peripheral tissues. Chylomicron transports triglyceride from the gut to the peripheral tissues.
The major production of HDL occurs in the liver. Studies have reported that the HDL has a closer inverse
High-density
association with atherosclerosis. HDL shows an inverse relationship with plasma LDL and triglyceride levels.
3. lipoprotein
Insulin treatment in type1 DM restores HDL to normal range. In type DM, HDL concentration is favourably
(HDL)
associated with female sex, weight loss, cessation of smoking, exercise and low intake of alcohol.

Low-density The rate of LDL secretion from the liver is influenced by diet, insulin, degree of adiposity etc; therefore, a wide
4. lipoprotein variability in its level is common. High level of plasma LDL has been shown to be associated with atherosclerosis
(LDL) and macro-vascular complications.
 Target of blood lipids
Target of blood lipids is set to protect cardiovascular risk. It is dependent on:
 Presence of cardiovascular disease, e.g. coronary artery disease (CAD) or equivalent conditions
 Diabetes mellitus (is considered as a CAD risk equivalent)
 Number of CVD risk factors present

Target of blood lipids for people with diabetes mellitus

1. LDL cholesterol <100 mg/dl (<70 mg/dl in overt CVD)
2.Triglyceride <150 mg/dl
3.HDL cholesterol >40 mg/dl (in male), >50 mg/dl (in female)
N.B: based on NCEP-ATP III guideline
 Dyslipidema Management

Studies have shown that LDL cholesterol is the Medical nutrition therapy-
Screening for
dyslipidemia

Treatment strategy of
dyslipidemia in diabetes

Non-pharmacological
interventions
correction of dyslipidemia primary target in plenty of vegetables and
very effectively helps to dyslipidemia treatment. At fruits; reduced total fat,
reduce the risk of initiation, non- saturated fat (<7%) and
developing CVD in persons pharmacological measures dietary cholesterol (<200
with diabetes. A lipid should be followed in all mg/day)
profile examination at diabetic persons with Weight loss for obese
baseline and annually dyslipidemia. After 3
thereafter is therefore months of lifestyle Regular exercise
recommended in all adults measures pharmacological Limitation of alcohol
with diabetes intervention is to be
undertaken
 Pharmacological interventions
Pharmacological interventions can be made with any of the following drug(s) according to the
pattern of dyslipidemia. For dosage schedule follow standard text books.

Groups Drugs Remarks

a. Atorvastatin
b. Fluvastatin a. Lowers LDL
Statin (inhibits HMG-CoA reductase activity) c. Rosuvastatin b. Lowers triglyceride
d. Pitavastatin c. Raises HDL
e. Simvastatin
Fibrate (stimulates lipoprotein lipase activity; a. Fenofibrate a. Lowers triglyceride
increases VLDL breakdown) b. Gemfibrozil b. Raises HDL
a. Lowers LDL
Nicotine acid (inhibits production of VLDL) a. Nicotine acid b. Lowers triglyceride
c. Raises HDL
Cholestyramine (prevents intestinal absorption of
a. Cholestyramine a. Lowers LDL
cholesterol)
Ezetimibe (prevents intestinal absorption of
I. Ezetimibe a. Lowers LDL
cholesterol)
a. Contains omega-3 fatty acids-
a. Lowers triglyceride
Fish oil (inhibits production of VLDL) eicosapentaenoic acid and
b. Raises HDL
docosahexaenoic acid
 Aspirin use in Diabetes

Aspirin (75-150 mg/day) Aspirin (75-150 mg/day) It can also be

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is to be used as is to be used as primary considered in age group
secondary prevention prevention of CVD in less than the above in
strategy of CVD in diabetics with age >50 presence of multiple
those with history of years in male and >60 cardiovascular risk
CVD years in female, with factors
hypertension,
dyslipidemia, family
history of CVD,
albuminuria or smoking

Clopidogrel may be an alternative

 Diabetic Foot
There are several reasons why foot of a diabetic person is vulnerable to lesion.
These include
Loss of Poor Higher

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sensation - circulation - likelihood of
neuropathy peripheral developing
vascular infections
disease
Diabetic foot ulcers are the most common cause for prolonged hospitalization. Lifetime risk of foot ulcer
in diabetes is about 25%.
Diabetes is the most important cause of non-traumatic foot amputations; 50% of these patients have
diabetes. After amputation mortality rate reaches 40-80%.
 Foot lesions in diabetes

Wagner’s grading of diabetic lesions

GradeDescription of lesion
0 No ulcer but high risk foot
1 Superficial ulcer
2 Deep ulcer but no bony involvement, no abscess
3 Deep ulcer with abscess or bony involvement
4 Localized gangrene (at toe, heel)
5 Gangrene of whole foot
Wagner’s grading of diabetic lesions
Pathway of amputation
A foot is labeled as ‘High risk’ if one or more
of the 6 factors is/are present

1. Loss of protective sensation

2. Absent pedal pulses
3. Severe foot deformity
4. Limited joint mobility
5. History of foot ulcer
6. Previous amputation
Screening for high-risk foot in diabetic
person

Screening for high Follow-up of high

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risk foot should risk foot should
be done at initial be done every 3-6
visit and at least months
yearly thereafter
 Clinical assessment of foot

1. Previous history of ulcer or amputation.

2. Presence of thick nails, limited joint mobility and/ or bone deformity.
3. Evidence of infection or increased pressure e.g. erythema, heat, callus formation,
haemorrhage under a callus.
4. Peripheral vascular disease by examining peripheral pulses and by Doppler test (ABI-
Ankle-Brachial Index).
5. Impairment of fine t ouch using Semmes-Weinstein nylon monofilament.
6. Impaired thermal sensation using hot and cold test tubes separately.
7. Raised vibration perception threshold using biothesiometer or graduated tuning fork.
Clinical assessment of foot
 Foot care education for diabetics
• Because of the associated nerve damage,
a person with diabetes cannot sense • the toes, between the toes and the • Cut nails after a bath, when these
temperature changes. So to avoid heat sole, and look and feed for breaks in are soft and pliable.
injury, the following precautions must be the skin, cuts, scratches, bruises, • Cut nails straight, not too deep on
made known to them: blisters, sores and the sides.
• Do not have very hot baths. discolorationInspect feet regularly • Do not use sharp instrument to
• Avoid sitting too close to the heater or (preferably daily)-. clean under the nail, or in the
fire.
• Use a mirror or friend/ relative to aid grooves.
• Do not use hot fomentations.
better viewing. • In case of pain or difficulty in
• Avoid hot water bottles or electric
blankets in the bed at night. cutting, consult nurse or doctor.
• Avoid all possible injuries.
How to avoid
How to How to cut
heat injury to
inspect feet? nails?
the foot?
How to choose footwear for a person with diabetes?
Shoes must provide proper support to the foot.
Following points should be considered:
Components Recommendations
Shoes must be of the correct shape and size for the feet. It is important to draw the outline of the feet by placing them on paper.
Shape and size Then to cut this outline and carry it when buying shoes. The cut paper must fit the inside of the shoe properly without crimping or
folding anywhere. This would be the correct and comfortable shoe size.
Heel & sole Flat shoes should be chose. Thick, sturdy soles protect the feet from sharp objects.
Toe box rounded wide toe box gives more space to the feet.
Material Leather shoes help the feet breathe freely.
Shopping Shopping for shoes should be always in the evening when the feet are the largest.
Woolen/cotton socks are to be used. Knee-high socks, or socks with tight tops or rough seams should be avoided. Check the size of
Socks
the shoes wearing the thickest socks.
Slippers and sandals do not provide adequate support to the feet and should be avoided for full-day-wear. They should be used only
Slippers and sandals
for short periods like night-wear.
 Oral and skin care

• Besides foot lesions, elevated blood glucose increases the risk of dry mouth, gingivitis and periodontitis,
dental caries, tooth loss, oral infections, etc. Diabetics are also prone to develop various dermatological
problems. So it is very important to maintain adequate personal hygiene, regular dental check-up etc.
•
• Other complications and comorbidities
• Diabetes may affect skin, musculo-skeletal system and other tissues to cause a number of lesions.
• Diabetic individuals are very much prone to wide range of infections. Sometimes these are very difficult to
treat.
• Diabetic patients may have some comorbid conditions, e.g. fatty liver, depression and cognitive
impairment, cancer etc.
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