Microvascular complications of Diabetes Flashcards
What are the sites of microvascular complications?
Retinal arteries
Renal glomerular arterioles
Vasa nervosum
What are Vasa Nervosum
tiny blood vessels that supply nerve
What is the relationship of risk with rising HbA1c?
Extent of hyperglycaemia (as judged by HbA1c) is strongly associated with the risk of developing microvascular complications
What is the relationship at high HbA1c’s?
At higher HbA1c levels the line gets steeper
For a small increase in HbA1c you get a large increase in risk
What does the large risk increase mean for management?
Huge margins to gains from a small reduction in HbA1c
What is the relationship between hypertension and risk?
Clear relationship between rising systolic BP and risk of MI and microvascular complications in people with T2DM and T1DM
Therefore prevention of complications requires reduction in HbA1c and BP control
What other factors relate to the development of microvascular complications?
Severity of hyperglycaemia
Hypertension
Genetic factors – some people develop complications despite reasonable control
Hyperglycaemic memory – inadequate glucose control early on can result in higher risk of complications LATER, even if HbA1c improved
Duration? Glucose variability?
What is the mechanism of damage?
Oxidative stress
Production of advanced glycated end product which disrupts production of proteins
Local activation of pro-inflammatory cytokines
What are the main features of diabetic retinopathy?
main cause of visual loss in people with diabetes and the main cause of blindness in people of working age
early stages of retinopathy are all asymptomatic
therefore screening is needed to detect retinopathy at a stage at which it can be treated before it causes visual disturbance / loss
How is early detection of retinopathy achieved?
annual retinal screening, which involves retinal imaging: national screening programme.
People with advanced retinopathy are referred to a specialist for treatment and may be seen more frequently
What is the mechanism of diabetic neuropathy?
Hyperglycaemia leads to protein kinase C activation
Disruption of the endothelium
Retinal ischaemia (leaky vessels)
Vascular oedema
Releases factors that lead to retinal neovascularisation
What are the 3 stages of retinopathy?
Background
Pre-proliferative
Proliferative
Maculopathy, which can occur at any stage of retinopathy
What are the features of background retinopathy?
Hard exudates (cheese colour, lipid) Microaneurysms (“dots”) Blot haemorrhages
What are the features of pre-proliferative retinopathy?
Cotton wool spots also called soft exudates
Represent retinal ischaemia
What are the features of proliferative retinopathy?
Visible new vessels
On disk or elsewhere in retina
What are the features of maculopathy?
Hard exudates / oedema near the macula
Same disease as background, but happens to be near macula
This can threaten direct vision
How do you treat background retinopathy?
Continued annual surveillance
Feedback to person living with diabetes
How do you treat pre-proliferative retinopathy?
If left alone will progress to new vessel growth
So, early panretinal photocoagulation
How do you treat proliferative retinopathy?
Panretinal photocoagulation
How do you treat maculopathy?
Oedema: Anti-VEGF injections
Grid photocoagulation
What causes diabetic nephropathy?
Hypertension
Progressively increasing proteinuria
Progressively deteriorating kidney function
Classic histological features
How are people screened for diabetic nephropathy?
Actively screened for and monitored with by measurement of albumin in urine
This can be done in a spot urine sample (rather than a 24-hr collection) and expressed as a ratio to creatinine: Urine albumin creatinine ratio.
Why is nephropathy important?
Associated with progression to end-stage renal failure requiring haemodialysis
Healthcare burden
Associated with increased risk of cardiovascular events
What is the relationship between macro and micro vascular complications?
Microvascular complications increase risk for Macrovascular complications
What are the histological features of diabetic nephropathy?
GLOMERULAR CHANGES
Mesangial expansion
Basement membrane thickening
Glomerulosclerosis
What is the epidemiology of nephropathy?
Type 1 DM : 20-40% after 30-40 years
Type 2 DM : Probably equivalent – BUT
Age at development of disease
Ethnic differences
Age at presentation
How do you diagnose nephropathy?
Progressive proteinuria (urine ACR - Albumin:Creatinine ratio)
Increased blood pressure
Deranged renal function (eGFR)
Advanced: peripheral oedema
What are the ranges for microalbuminuria?
> 2.5 mg/mmol (men)
>3.5 mg/mmol (women)
What is the mechanism of nephropathy?
Diabetes associated with hypertension
High BP at glomerular level
Destruction of glomeruli
Interstitial fibrosis
Decreased GFR
What are the strategies for intervention for nephropathy?
Decreasing HbA1c reduces risk of microvascular complications
Manage blood pressure
Inhibit the renal-angiotensin-aldosterone system
SGLT-2 inhibition
Why does a blockade of RAS work?
Mediation of glomerular hyperfiltration
Increased tubular uptake of proteins
Induction of pro fibrotic cytokines
Stimulation of glomerular and tubular growth
Generation of ROS & NF-kB
Stimulates fibroblast proliferation
Up regulation of adhesion molecules on endothelial cells
Up regulation of lipoprotein receptors
Summarise nephropathy treatment?
- Aim for tighter glycaemic control
- Reduce BP as much as tolertated
- Usually through ACEi or A2RB
- Stop smoking
- Start an SGLT-2 inhibitor if T2DM?
What are the main features of diabetic neuropathy?
Diabetes is the most common cause of neuropathy and therefore lower limb amputation
Small vessels supplying nerves are called vasa nervorum
Neuropathy results when these get blocked
What are the different types of diabetic neuropathy?
Peripheral polyneuropathy Mononeuropathy Mononeuritis multiplex Radiculopathy Autonomic neuropathy Diabetic amyotrophy
Why are people with diabetes at risk of foot issues?
Longest nerves supply feet
Loss of sensation
More common in tall people
Danger is that patients will not sense an injury to the foot (eg. Stepping on a nail)
All people with diabetes: annual foot check with GP
What are the clinical features of peripheral neuropathy?
Loss of sensation (10g monofilament)
Loss of vibration sense
Loss of temperature sensation
Loss of proporioception
Loss of ankle jerks
Classic ‘glove and stocking’ distribution
Danger is no sense an injury to the foot (eg. Stepping on a nail)
How do you manage peripheral neuropathy?
- Regular inspection of feet by affected individual
- Good footwear
- Avoid barefoot walking
Podiatry and chiropody if needed
How do you manage peripheral neuropathy with ulceration?
Multidisciplinary diabetes foot clinic Offload pressure Revascularisation if concomitant Peripheral Vascular Disease Antibiotics if infected Orthotic footwear Amputation if all else fails
What is mononeuropathy?
Usually sudden motor loss
wrist drop, foot drop
Cranial nerve palsy:
double vision due to 3rd nerve palsy
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
What is autonomic neuropathy?
Loss of sympathetic and parasympathetic nerves to GI tract, bladder, cardiovascular system
What are the GI symptoms of autonomic neuropathy?
Difficulty swallowing
Delayed gastric emptying: nausea and vomiting
Constipation / nocturnal diarrhoea
Bladder dysfunction
What are the Cardiovascular symptoms of autonomic neuropathy?
Postural hypotension: can be disabling: collapsing on standing.
Cardiac autonomic supply: case reports of sudden cardiac death
