Diabetic Complications Flashcards
List the microvascular complications which can develop chronically in diabetes mellitus
Site of Microvascular Complications
- Retinal Arteries (diabetic retinopathy)
- Glomerular Arterioles (nephropathy)
- Vasa Vasorum (tiny blood vessels that supply the nerves 99> leads to neuropathy)
Factors that correlate with risk of microvascular and macrovascular complications
Glycaemic control (HbA1c) (hypoglycaemia)
Hypertension
Other factors such as glycaemic memory and genetics can contribute
Mechanism of glucose damage to blood vessels
Hyperglycaemia leads to oxidative stress and hypoxia
This triggers an inflammatory cascade, which leads to damage
Explain why microvascular complications develop in chronic diabetes mellitus: diabetic retinopathy
Diabetic Retinopathy
- This is the main cause of visual loss in people with diabetes and the main cause of blindness in people of working age
Normal Retina
- You look at the eye using a fundoscope
- When looking at a normal retina you will see the optic disc at the nasal part of the eye and the macula which is more lateral and is involved in colour vision and acuity
- There are various vessels that come out into the back of the retina and they usually have a very regular arrangement
Background Diabetic Retinopathy
- NOTE: there are FOUR different types of retinopathy
- You get hard exudates which appear as cheesy yellow spaces in the retina
- The hard exudates are caused by the leakage of lipid contents which make the back of the eye look a cheesy colour
- There will be microaneurysms
- These can rupture causing blot haemorrhages
Summary of the features of background diabetic retinopathy:
- Hard exudates
- Microaneurysms
- Blot haemorrhages Pre-proliferative Diabetic Retinopathy
- Cotton wool spots called SOFT EXUDATES
- The soft exudates show retinal ischaemia
- This shows several haemorrhages and it shows the soft exudates looking ‘fluffy’
Proliferative Retinopathy
- This involves the formation of new vessels
- This can be on the optic disc or elsewhere in the retina
- The new vessels form as a response to the retinal ischaemia
- If the vessels form in the region of the macula, it can cause problems with acuity and colour vision
- These new vessels are generally more fragile so they can bleed at any time
Maculopathy
- You get hard exudates near the MACULA
- This is the same disease as background diabetic retinopathy, the only difference is that the hard exudates form near the macula
- This can threaten direct vision
Summary of the different types of retinopathy
- Background Diabetic Retionpathy
- Pre-proliferative Retinopathy
- Proliferative Retinopathy
- Maculopathy
Management of diabetic retinopathy
Management of Diabetic Retinopathy
Background
- Improve control of blood glucose
- Warn patient that the warning signs are there
Pre-proliferative
- You see the cotton wool spots (soft exudates) which suggest retinal ischaemia
- If left alone, this will progress to proliferative retinopathy with vessel growth
Treatment: pan-retinal photocoagulation
- You laser the retina and stop the vessels from bleeding
Proliferative
- Also needs pan-retinal photocoagulation
Maculopathy
- There is only a problem around the macula
- This means you only need a GRID of photocoagulation in the affected area
- This is NOT pan-retinal photocoagulation
Discuss diabetic nephropathy
Features of Diabetic Nephropathy
- Hypertension
- Progressively increasing proteinuria
- Progressively deteriorating kidney function
- Classic histological features
Having diabetes and chronic kidney disease increases your risk of cardiovascular events dramatically
Overview of the Histological Features of Nephropathy
- Glomerular
- Vascular
- Tubointerstitial
Glomerular Changes
- Mesangial expansion
- Basement membrane thickening
- Glomerulosclerosis (hardening of the capillaries)
- The glomerulus becomes less flexible and harder
- The absorption of nutrients can change so you get more pressure going through the kidneys
- This can lead to changes in blood pressure control
- Essentially, in diabetic nephropathy there is overproduction of matrix leading to mesangial expansion and to basement membrane thickening
- As this is progressing, you get sclerosis of the glomerulus and secondary effects on the tubulointerstitium
- There are several stimuli for these processes including the effects of prolonged exposure to high glucose or glycosylated proteins in at risk patients
- Also, a rise in the pressure within the glomerular capillaries can stimulate expansion of the matrix
- Angiotensin stimulates pathways that result in overproduction of matrix
- Angiotensin can also cause the constriction of the efferent arterioles, thus increasing transglomerular capillary pressure
Epidemiology of Diabetic Nephropathy
T1DM = 20940% after 30940 years
T2DM = probably equivalent
Epidemiology of Diabetic Nephropathy in T2DM
- Age at development of disease will affect the epidemiology
- Racial factors
- Age at presentation
- Loss due to cardiovascular morbidity
Clinical Features of Diabetic Nephropathy
- Progressive proteinuria
- Increased blood pressure
- Deranged renal function Proteinuria
It is measured using urine dipsticks
As the urinary excretion of albumin is increased, their serum albumin will be low and so they tend to be quite oedematous
This is because, with less protein in the serum, there is less osmotic potential drawing water into the circulation out of the cells
Management of diabetic nephropathy
Strategies for Intervention
- Diabetic control
- The lower the HbA1c the lower the risk of microvascular complications
- Blood pressure control
- Control of blood pressure will slow down the deterioration in kidney function
- Inhibition of the activity of the renin-angiotensin system
- ACE inhibitors reduce the rate of decline of creatinine thus reducing the rate of deterioration of kidney function
- Stopping smoking
Angiotensin II
- All of these changes make the endothelial cells more rigid
Renin Angiotensin System
- Renin is produced by the juxtaglomerular apparatus
- If you have low perfusion (i.e. low blood pressure) then the renin levels will increase
- ACE is found in the lungs
- There are various places where this system can be targeted:
- Drugs blocking renin activity
- ACE inhibitors
- AT1 antagonists
- NOTE: Irbesartan is an angiotensin II receptor antagonist
Diabetic Neuropathy
Diabetic Neuropathy
- Diabetes is the most common cause of neuropathy and, therefore, lower limb amputation
- The small vessels supplying the nerves are called the vasa vasorum
- Neuropathy results when the vasa vasorum gets blocked
Types of Diabetic Neuropathy:
- Peripheral polyneuropathy
- Mononeuropathy
- Mononeuritis multiplex
- Radiculopathy
- Autonomic neuropathy
- Diabetic amyotrophy
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NOTE: there is an interplay between genetics and the inflammatory cascade which then causes the diabetic neuropathy to occur
Peripheral Neuropathy
- This affects their hands and feet 9 ‘gloves and stockings distribution’
- Peripheral neuropathy is most likely to occur in:
- Tall patients
- Patients with poor glucose control
- You can test this with the monofilament examination (where you prick the patient’s foot with a filament)
- Peripheral neuropathy also leads to the loss of ankle jerks and loss of vibrational sense (using a tuning fork)
- There may be multiple fractures on the foot X-ray (Charcot’s joints)
Mononeuropathy
- Usually sudden motor loss
- Can get wrist drop or foot drop
- Cranial nerve palsy
E.g. double vision due to cranial nerve palsy
- Pupil sparing third nerve palsy
- The eye is usually down and out because of the unopposed action of lateral rectus and superior oblique
- The pupil DOES respond to light
- The parasympathetic fibres are on the outside -> So they do NOT lose blood supply in diabetes
- Aneurysm causing third nerve palsy - It will press on the parasympathetic fibres first
- This causes a fixed dilated pupil
- So a fixed dilated pupil with 3rd nerve palsy is NOT DUE TO DIABETES
Mononeuritis Multiplex
- A random combination of peripheral nerve lesions
- Radiculopathy
- Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall
Autonomic Neuropathy
- Loss of sympathetic and parasympathetic nerves to the GI tract, bladder and cardiovascular system
- Effects of autonomic neuropathy on the GI tract:
- Difficulty swallowing
- Delayed gastric emptying
- Constipation/nocturnal diarrhoea
- Bladder dysfunction
- Effects of autonomic neuropathy on the cardiovascular system:Postural hypotension
- Can be disabling 9 collapsing on standing
- Cardiac autonomic supply
- Case reports of sudden cardiac death
- Checking for autonomic neuropathy:Measure changes in heart rate in response to the Valsalva manouevre
- You make them blow into a tube and this normally causes a change in heart rate
- Look at ECG and compare the RKR intervals
Hyperglycaemia is a risk factor for arterial disease
Development of Atheroma
- This is a life long issue
- Small accumulations of extracellular lipid will lead to atheroma which then leads to fibroatheroma
- It could then lead to a complicated lesion which can ulcerate, exposing the fat underneath and this can either thrombose entirely or send emboli further down the circulation
- Initially, this process begins with accumulation of lipid but progresses to involve smooth muscle
- This can lead to smooth muscle hypertrophy, fibrosis and calcification
Hyperglycaemia is part of a spectrum of arterial disease that significantly reduces life expectancy
- Metabolic syndrome has been associated with hyperglycaemia
- NOTE: area under curve (AUC) insulin is a marker of insulin resistance
- The more insulin resistant you are, the shorter the lifespan
- The relative risk of cardiovascular events in women with diabetes tend to be increased but this is because women tend to be protected from atheroma in general in their reproductive years, but with diabetes, this relative benefit is lost
- This is why the relative risk in women appears to be much worse than in men
- The risk of microvascular disease is very much related to sugar so people without diabetes have virtually no risk of microvascular disease
- The risk associated with HbA1c and macrovascular disease is more linear 9 the higher the HbA1c, the greater the risk of macrovascular disease
- Even people without diabetes have a relatively high risk of macrovascular disease
Cardiovascular mortality in people with diabetes is elevated
Patients with diabetes die from diseases of big arteries
Microvascular disease causes morbidity
Macrovascular disease causes morbidity AND mortality
Cause of Death
In diabetes, the age9adjusted mortality from ischaemic heart disease gives a risk of about 60%
Malignancy appears to be decreased in diabetes but this is because diabetic patients are likely to have died before the age at which patients tend to get cancer
Diabetes mortality over time compared to those with known coronary artery disease
If people have had one heart attack, they are more likely to have another
People with diabetes who have NOT had a heart attack, have the same mortality as someone without diabetes who has had a heart attack
Even someone with diabetes who appears well is likely to have ischaemic heart disease
NOTE: the Framingham risk score is a gender9specific algorithm used to estimate the 109year cardiovascular risk of an individual
NOTE: for a given cholesterol, South Asians have an increased risk of coronary heart disease mortality
Management of glucose alone does not address vascular risk
Treatment targeted to blood glucose alone does NOT significantly offset the increased risk of cardiovascular disease
- Intensive glucose control does improve coronary heart disease risk
- But it did not translate to much of a change in mortality
Aggressive management of all modifiable risk factors is required
Prevention of macrovascular disease requires aggressive management of multiple risk factors
Risk factors for macrovascular disease
So blood pressure and cholesterol also need to be managed in the treatment of diabetes and the prevention of macrovascular complications
It was found that taking a statin had a significant reduction in macrovascular disease risk
The patients were less likely to have a stroke/heart attack by nearly a half
So if we treat cholesterol AND blood pressure, you can achieve a dramatic reduction in macrovascular disease risk
Glycated Haemoglobin
Series of Hb components formed by adduction of glucose or glucose9derived products to normal adult HbA
Associated with risk of complications
Blood Pressure Management
Macrovascular disease is a systemic disease of multiple arterial beds
Macrovascular disease is a systemic disease and is commonly present in multiple arterial beds
Ischaemic Heart Disease
- The major cause of morbidity and mortality in diabetes
- The mechanisms are similar with or without diabetes
Cerebrovascular Disease
- Earlier than without diabetes
- More widespread
- This is uncommon in people younger than 60
Peripheral Vascular Disease
- Contributes to diabetic foot problems with neuropathy
Renal Artery Stenosis
- May contribute to hypertension in some
