Microvascular Diabetic Complications Flashcards
What are the sites for microvascular complications?
- Retinal arteries
- Renal glomerular arterioles
- Vasa nervorum - tiny blood vessels that supply nerve
Is there a risk between rising HbA1c and risk of developing microvascular complications?
Extent of hyperglycaemia (as judged by HbA1c) is strongly associated with the risk of developing microvascular complications - line gets steeper, and still always risk of complications
Is there a risk between rising systolic BP and risk of developing microvascular complications and MI?
Clear relationship between rising systolic BP and risk of MI and microvascular complications in people with T2DM and T1DM
What do you need to reduce to prevent complications?
BP and HbA1c
What are other factors related 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 diabetic retinopathy?
main cause of visual loss in people with diabetes and the main cause of blindness in people of working age
Why do you need to screen for diabetic retinopathy?
- early stages of retinopathy are all asymptomatic
- screening is needed to detect retinopathy at a stage at which it can be treated before it causes visual disturbance / loss
What happens if there is advanced retinopathy?
referred to a specialist for treatment and may be seen more frequently
What are the stages of retinopathy?
- Background retinopathy
- Pre-proliferative retinopathy
- Proliferative retinopathy
- Also maculopathy, which can occur at any stage of retinopathy
What is background retinopathy?
- Hard exudates (cheese colour, lipid)
- Microaneurysms (“dots”)
- Blot haemorrhages
What is pre-proliferative retinopathy?
- Cotton wool spots also called soft exudates (not as crisp as hard exudates)
- Represent retinal ischaemia
What is proliferative retinopathy?
- Visible new vessels
2. On disc or elsewhere in retina
What is maculopathy?
- Hard exudates near the macula
- Same disease as background, but happens to be near macula
- This can threaten direct vision
What is the treatment of background retinopathy?
- Improve HbA1c
- Good BP control
- Continued annual surveillance
- Feedback to person living with diabetes
What is the treatment of pre-proliferative retinopathy?
- Improve HbA1c
- Good BP control
- If left alone will progress to new vessel growth
- S early pan retinal photocoagulation (burns vessels off to stop new vessel forming)
What is the treatment of proliferative retinotherapy?
- Improve HbA1c
- Good BP control
- Panretinal photocoagulation
How do you treat diabetic maculopathy?
- Improve HbA1c
- Good BP control
- Odema: Anti-VEGF injections
- Grid photocoagulation. (burns vessels off to stop new vessel forming - more localised than pan)
What is diabetic nephropathy characterised by?
- Hypertension
- Progressively increasing proteinuria
- Progressively deteriorating kidney function
- Classic histological features
Is everyone at risk of developing diabetic nephropathy?
-People with any type of diabetes is at risk of developing diabetic nephropathy
How do you screen and monitor diabetic nephropathy?
measurement of albumin in urine
How do you measure albumin in urine?
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 are the glomerular changes in nephropathy?
- Mesangial expansion
- Basement membrane thickening
- Glomerulosclerosis
What is the epidemiology of developing 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
•Loss due to cardiovascular morbidity
What is the diagnosis of diabetic nephropathy?
- Progressive proteinuria (urine ACR)
- Increased blood pressure
- Deranged renal function (eGFR)
- Advanced: peripheral oedema
How do. you intervene for diabetic nephropathy?
1) Decreasing HbA1c reduces risk of microvascular complications
2) Manage blood pressure
3) Inhibit the renal-angiotensin-aldosterone system (ACE inihibtor)
4. SGLT-2 inhibition (not yet.)
Why does the blockade of RAS work?
- Stops effect of ANGIOTENSIN at. glomerular level 2 proinflammtory
1. Mediation of glomerular hyperfiltration
2. Increased tubular uptake of proteins
3. Induction of pro fibrotic cytokines
4. Stimulation of glomerular and tubular growth
5. Generation of ROS + NF-kB
6. Stimulates fibroblast proliferation
7. Up regulation of adhesion molecules on endothelial cells
6. Up regulation of lipoprotein receptors
What is the treatment summary for nephropathy?
- 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 is 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
When is diabetic neuropathy most common?
- Longest nerves supply feet so starts in feet
- Loss of sensation
- More common in tall people
Why can diabetic neuropathy be dangerous?
- 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 -Glove and stocking distribution
What is the management of peripheral neuropathy with no ulceration?
- Regular inspection of feet by affected individual
- Good footwear
- Avoid barefoot walking
- Podiatry and chiropody if needed
What is the management of peripheral neuropathy with ulceration?
- Multidisciplinary diabetes foot clinic
- Offloading
- Revascularisation if concomitant PVD
- Antibiotics if infected
- Orthotic footwear
- Amputation if all else fails
What are other types of neuropathies?
- Peripheral polyneuropathy
- Mononeuropathy
- Mononeuritis multiplex
- Radiculopathy
- Autonomic neuropathy
- Diabetic amyotrophy
What is mononeuropathy?
1. Usually sudden motor loss wrist drop, foot drop 2. Cranial nerve palsy: double vision due to 3rd nerve palsy 3. Pupil sparing, as parasympathetic fibres not comprised (not pressure on third nerve as in other causes of third nerve)
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 are the effects of autonomic neuropathy to the GI tract?
- Difficulty swallowing
- Delayed gastric emptying: nausea and vomiting
- Constipation / nocturnal diarrhoea
- Bladder dysfunction
What are the effects of autonomic neuropathy to the cardiovascular system?
- Postural hypotension: can be disabling: collapsing on standing.
- Cardiac autonomic supply: case reports of sudden cardiac death
How do you diagnose autonomic neuropathy?
- Diagnose on R-R interval changes
- Or no change in heart rate on Valsalva manourvre
- Gastric emptying studies
What is the mechanism of damage?
- Hyperglycaemia and hyperlipodemia
- Oxidative stress, AGE rage (proteins become glycated and disrupt function) and hypoxia
- Inflammatory signalling cascades
- Local activation of pro-inflammatory cytokines
- Inflammation
- Nephropathy/ Retinopathy/Neuropathy
What is the mechanism for diabetic retinopathy?
- Hyperglycaemia
- Oxidative stress, AGE, PKC activation, Inflammation, RAS
- Vascular endothelial dysfunction
- Retinal ischaemia
- Produces CA, VEGF, GH-IGF and Erythropeitn that increases permeability of vascular so leakiness out of blood vessels into tissues where they shouldn’t be
- Result in macular oedema, and from retinal neovascularation to PDR complication
What are the microalbuminuria levels in nephropathy?
> 2.5 mg/mmol (men)
3.5 mg/mmol (women)
if album >30mg/mmol protein uria
What is the mechanism for diabetic nephropathy?
- Hyperglycaemia and associated hypertension
- Glomerular hypertension
- Proteinuria
- Glomerular and interstilital fibrosis
- Glomerular filtration rate. decline
- Renal failure
