Microvascular complications of diabetes mellitus Flashcards
State the three main sites of microvascular complications.
Retinal arteries (retinopathy) Glomerular arterioles (nephropathy) Vasa vasorum (neuropathy)
What factors correlate with risk of microvascular complications?
- Poor glycaemic control (HbA1c) => hyperglycaemia
- Hypertension
- Genetics
- Hyperglycaemic memory
- Tissue damage through originally reversible and later irreversible alterations in proteins
Describe the overarching mechanism of glucose damage to blood vessels.
Hyperglycaemia leads to oxidative stress and hypoxia
This triggers an inflammatory cascade, which leads to damage
What instrument is used to look into the eye?
Fundoscope
Where is the optic disc relative to the macula on the back of the eye?
The optic disc (optic nerve head) is nasal to the macula/fovea (functional center of the retina = light sensitive tissue)
What are the 4 types of diabetic retinopathy?
- Background
- Pre-proliferative
- Proliferative
- Maculopathy
What three features do you see in background diabetic retinopathy?
Hard exudates ('cheese' colour, lipid)
Microaneurysms ('dots')
Blot haemorrhagesWhat are hard exudates caused by?
Leakage of lipid contents makes the back of the eye look a cheesy colour
Why is background diabetic retinopathy considered a warning sign that blood glucose control overall is poor? What must you convey to the patient (in terms of management)?
Patients have normal vision, and will have no idea that they have a problem.
If not improved more complications will occur so patients should be informed that they have background retinopathy, and a real effort to improve glucose control must be made.
Describe pre-proliferative diabetic retinopathy.
- Soft exudates (cotton wool spots) which represent retinal ischaemia
- The ischaemia is associated with the release of angiogenic factors which will stimulate the formation of new blood vessels to improve blood flow (but this is problematic)
Describe proliferative diabetic retinopathy.
- If the ischaemia is not treated, or not noticed, then new blood vessels may grow. If new vessels are observed, this is known as proliferative retinopathy.
- The new vessels are generally more fragile so that minimal trauma can cause bleeding into the vitreous humour of the eye => instantaneous blindness
Describe maculopathy.
Presence of hard exudates in the macula
Note that this is the same disease as background diabetic retinopathy, it’s just that the hard exudates are in the macula; this can threaten direct vision.
What is the treatment for pre-proliferative and proliferative diabetic retinopathy?
Pan-retinal photocoagulation (laser treatment to sacrifice peripheral retina that is not essential for normal vision thus preventing bleeds)
Describe the treatment of maculopathy.
Localised laser/photocoagulation grid therapy (aim to limit damage to the macula)
State 3 clinical features of diabetic nephropathy.
- Hypertension
- Progressively increasing proteinuria
- Progressively deteriorating kidney function
State some histological features of diabetic nephropathy.
- Mesangial expansion (the mesangium is a structure associated with the capillaries in the glomerulus)
- Basement membrane thickening
- Glomerulosclerosis (hardening of the capillaries)
In diabetic nephropathy you get over production of matrix. What can this be caused by?
Effects of prolonged exposure to high glucose or glycosylated proteins
A rise in pressure within the glomerular capillaries
Angiotensin II
What is the normal range and nephrotic range for proteinuria?
< 30 mg/24hr
> 3000mg/24hr
Why do patients with diabetic nephropathy get oedematous?
Increased proteinuria/albuminuria => decreased serum albumin hence decreasing the osmotic potential of the plasma so less fluid is drawn back into the circulation
State some strategies for intervention of patients with diabetic nephropathy.
- Improve blood glucose control
- Improve blood pressure control
- Inhibition of the activity of the renin-angiotensin system
- Stopping smoking
State some drug target sites in the renin-angiotensin system.
- Drugs blocking renin activity
- ACE inhibitors
- Angiotensin II receptor blockers (ARBs)
What causes diabetic neuropathy?
Occlusion of the vasa vasorum (Small vessels supplying nerves)
State 6 different types of diabetic neuropathy.
Peripheral polyneuropathy Mononeuropathy Mononeuritis multiplex Radiculopathy Autonomic neuropathy Diabetic amyotrophy
What can peripheral neuropathy lead to? Who are most susceptible?
- Loss of sensation in feet (since longest nerves supply feet); danger is that patients will not sense an injury to the foot
- Loss of ankle jerks
- Loss of vibration sense (using tuning fork)
- Multiple fractures on foot X-ray (described as Charcot’s joint/foot)
More likely to occur in:
- tall patients
- patients with poor glucose control
How can peripheral neuropathy be tested?
Monofilament examination
What is mononeuropathy?
Usually sudden motor loss e.g. wrist drop or foot drop
- Can also cause cranial nerve palsy (e.g. double vision due to 3rd nerve palsy)
Why is the pupil spared in pupil sparing third nerve palsy?
- Eye is usually “down and out” (6th nerve pulls eye out and 4th nerve pulls it down).
- But since the parasympathetic fibres, responsible for controlling the diameter of the pupil, run on the outside of the main nerve, they don’t easily lose their blood supply in diabetes
How would an aneurysm causing third nerve palsy present differently to third nerve palsy caused by diabetes?
The aneurysm will press on parasympathetic fibres first causing a fixed dilated pupil
What is mononeuritis multiplex?
A term used to describe a distinctive clinical presentation of progressive, random motor and sensory deficits in the distribution of specific peripheral nerves.
What is radiculopathy?
Compressed spinal nerve causing pain and other symptoms
What are the effects of autonomic neuropathy on the GI tract (and bladder)?
Difficulty swallowing
Delayed gastric emptying
Constipation/nocturnal diarrhoea
Bladder dysfunction
What are the effects of autonomic neuropathy on the CVS?
- Postural hypotension
- Affected cardiac autonomic supply (case reports of sudden cardiac death)
How can you check for autonomic neuropathy?
- Measure changes in heart rate in response to Valsalva manoevre (should be a change)
- Look at ECG and compare R-R intervals
