Endo 18: Microvascular complications of diabetes Flashcards
3 sites of microvascular complication
Retinal arteries
Glomerular arterioles (kidney)
Vasa nervorum (tiny blood vessels that supply nerves)
What determines microvascular complications
- Severity of hyperglycaemia
- Affects retinopathy the most, then nephropathy then neuropathy - HTN
- Genetic
- Hyperglycaemia memory
What causes microvascular complications, generally
Tissue damage through originally reversible and later irreversible alterations in proteins
What is hyperglycaemia memory
The fact that previous glucose control affects microvascular outcomes at a given time
How does hyperglycaemia cause microvascular damage?
High glucose levels cause many changes in the inflammatory cascades.
This then leads to inflammation, causing problems in the eyes, kidneys and nerves.
There are pathways that make this damage worse:
- Polyol pathway
- AGEs
- Protein kinase C
- Hexosamine
What is the main cause of blindness in people of working age
Diabetic retinopathy is the main cause of visual loss in people with diabetes and the main cause of blindness in people of working age
Outline the cause of proliferative diabetic retinopathy
Hyperglycaemia leads to inflammation (polyol, AGEs, PKC, hexosamine etc)
This leads to vascular endothelial dysfunction. Hypertension also leads to this.
This all leads to retinal ischaemia, promoting VEGF and erythropoietin.
There is increased vascular permeability, leading to diabetic macular oedema, and RETINAL NEOVASCULARISATION, leading to PDR compliations
What will be see in background diabetic retinopathy
Hard exudates (cheese colour, lipid)
Microaneurysms (“dots”)
Blot haemorrhages
What is seen in pre-proliferative diabetic retinopathy
Cotton wool spots also called soft exudates
Represent retinal ischaemia
What is seen in proliferative retinopathy
Visible new vessels
On disk or elsewhere in retina
What is maculopathy
Hard exudates near the macula
T/F maculopathy has a distinct pathological process to background diabetic retinopathy
NO!
It’s background diabetic retinopathy, but happens to be near macula
Can threaten direct vision
Management of background diabetic retinopathy
Background:
- improve control of blood glucose
- warn patient that warning signs are present
Management of pre-proliferative diabetic retinopathy
If left alone, new vessels WILL grow
Needs: Pan retinal photocoagulation
Management of proliferative diabetic retinopathy
Also needs:
-Pan retinal photocoagulation
In which case would you need to use photocoagulation when you only have background retinopathy
Maculopathy
Only have problem around macula
Needs only a GRID of photocoagulation
(NOT pan retinal photocoagulation)
What is diabetic nephropathy
Hypertension
Progressively increasing proteinuria
Progressively deteriorating kidney function
Classic histological features
T/f diabetic nephropathy is associated with morbidity not mortality
F… both
What is the most significant set of risk factors for cardiovascular disease
Diabetes and CKD
Histological features at the glomerulus in nephropathy
Mesangial expansion
Basement membrane thickening
Glomerulosclerosis
What might indicate that a patient’s kidney problems are not due to diabetes
If retinopathy has not already been detected
What is the proportion of diabetics getting nephropathy
Type 1 DM: 20-40% will have nephropathy after 30-40 years
• Type 2 DM: Probably equivalent – BUT there are a few caveats
What affects the likelihood of a T2DM patient getting nephropathy
Age at development of disease
Racial Factors
Age at presentation
Loss due to cardiovascular morbidity
Clinical features of diabetic nephropathy
Progressive proteinuria
Increased BP
Deranged renal function
What are the ranges of proteinuria
Normal Range <30mg/24hrs
Microalbuminuric Range 30 - 300mg/24hrs
Assymptomatic Range 300 - 3000mg/24hrs
Nephrotic Range >3000mg/24hr
Strategies for control of diabetic nephropathy
- Diabetic control (37% decrease in risk of microvascular complications per 1% decrement in HbA1c)
- BP control
- Control of the RAS
- Smoking cessation
How does BP control affect GFR
It reduces the rate of deterioration of GFR in patients with diabetic nephropathy
Which antihypertensive is used in diabetic retinopathy
ACEi
Effects of angiotensin II
Vasoactive effects Mediation of glomerular hyperfiltration Increased tubular uptake of proteins Induction of pro fibrotic cytokines Stimulation of glomerular and tubular growth Podocyte effects Induction of pro inflammatory cytokines Generation of ROS & NF-kB Stimulates fibroblast proliferation Up regulation of adhesion molecules on endothelial cells Up regulation of lipoprotein receptors
Which parts of the RAS are targets in diabetic nephropathy
Renin
ACE
AT1
What is the name of small arteries supplying nerves
Vasa nervorum
What is the problem with the nerves in diabetes
The small blood vessels to the nerves (vasa nervorum) are blocked= neuropathy
What is the most common cause of limb amputation
Diabetes
What types of neuropathy can you get in diabetic neuropathy
Peripheral polyneuropathy Mononeuropathy Mononeuritis multiplex Radiculopathy Autonomic neuropathy Diabetic amyotrophy
Which peripheral nerves are longest
Longest nerves supply feet
What does peripheral nephropathy result in and who is it most common in
Loss of sensation
More common in tall people and patients with poor glucose control
What is the danger with peripherla neuropathy
Danger is that patients will not sense an injury to the foot (eg. Stepping on a nail)
What signs can be seen on peripheral neuropathy
Loss of ankle jerks
loss of vibration sense (using tuning fork)
multiple fractures on foot X-ray (Charcot’s joint)
What signs are seen in mononeuropahty
Usually sudden motor loss
wrist drop, foot drop
Cranial nerve palsy:
double vision due to 3rd nerve palsy
What eye sign is seen in mononeuropathy
Eye is usually “down and out”.
(6th nerve pulls eye out and 4th nerve pulls it down).
Pupil DOES respond to light.
Why does mononeuropathy not involve the pupil
parasympathetic fibres on outside.
Thus they do not easily lose blood supply in diabetes
Signs of aneurysm causing 3rd nerve palsy
Will press on parasympathetic fibres first causing fixed dilated pupil
In diabetes this is NOT the case
What is mononeuritis multiplex
A random combination of peripheral nerve lesions
What is radiculopathy
Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall.
What is autonomic neuropathy
Loss of sympathetic and parasympathetic nerves to GI tract, bladder, cardiovascular system.
How might autonomic neuropathy affect GI tract
GI tract: difficulty swallowing delayed gastric emptying constipation / nocturnal diarrhoea Bladder dysfunction
What is worrying with autonomic neuroapathy
Postural hypotension
can be disabling: collapsing on standing.
Cardiac autonomic supply
case reports of sudden cardiac death
How can autonomic neuropathy be detected
Measure changes in heart rate in response to Valsalva manoevre
Normally there is a change in heart rate
Look at ECG and compare R-R intervals
