Microvascular Diabetic Complications Flashcards
What are the 3 major sites of damage from hyperglycaemia?
Retinal arteries
Renal glomerular arterioles
Vasa nervorum - tiny blood vessels that supply nerves
Which of the following is associated with the development of microvascular complications?
Lower HbA1c
High cholesterol level
Hypertension
Shorter duration of diabetes
Hypertension
What is the relationship between risk of developing microvascular complications and HbA1c?
Rising HbA1c = increasing risk of microvascular complications
Exponential curve, normal HbA1c = still slight risk of microvascular complications
How does increased microvascular complications relate to development of MI?
Increased microvascular complications = increased risk of MI
So increased HbA1c = increased microvascular complications = increased risk of MI
Exponential curve
Using what increases microvascular complications, what else would you control in T2DM patients?
HbA1c
BP (particularly hypertension)
What other factors contribute to the development of microvascular complications?
Severity of hyperglycaemia
Hypertension
Genetic factors - some people develop the complications despite reasonable control
Hyperglycaemic memory - inadequate glucose control early on can result in higher risk of complications later, even is HbA1c has improved
Longer duration of high HbA1c = higher risk of microvascular complications
What is the mechanism of damage to the rising of the microvascular complications?
There is oxidative stress due to hyperglycaemia and hyperlipidemia
Advanced glycated end-products (i.e. glucose combined with lipids or proteins) - affects proteins
Then leads to activation of pro-inflammatory cytokines = causes inflammation
Leads to the 3 microvascular complications
What are the 3 microvascular complications?
The 3 pathies:
Nephropathy
Retinopathy
Neuropathy
What is diabetic retinopathy?
Main cause of visual loss in people with diabetes
Early stages of retinopathy are all asymptomatic, therefore screening is needed to detect retinopathy at a stage which can be treated before visual loss
How does diabetic retinopathy develop?
Activation of multiple factors that should not be activated
Leads to vascular endothelial dysfunction - can lead to retinal ischaemia
This can increase leakiness (vascular permeability) of vessels
Factors can leak out of the vessels, including erythropoeitin (stuff RBCs are made out of)
This can lead to formation of new blood vessels on the retina - retinal neovascularisation
What are the stages of retinopathy?
What do they look like on retina screens / images?
Background retinopathy - present on the retina as: hard exudates (yellow dots), microaneurysms (red dots), blot haemmorhages
Pre-proliferative retinopathy - present on the retina as: soft exudates (fuzzy, cotton wool spots) - represent retinal ischaemia
Proliferative retinopathy - present on the retina as: neovascularisation (formation of new vessels) due to ischaemia - squiggly vessels as they are fragile
Maculopathy can attack at any of these stages - present on the retina specifically over the macula
What is the treatment of retinopathy?
For all stages: improve HbA1c and BP control
Background: Annual checks, feedback to person with diabetes
Pre-proliferative and proliferative:
Pan-retinal photocoagulation - burn off new vessel formation using laser (across the retina)
Grid laser therapy - treat new blood vessel formation (across macula)
What is diabetic nephropathy? How is it diagnosed?
Due to hypertension
Progressively increasing proteinuria
Progressively deteriorating kidney function
Actively screened for
How is it diagnosed?
Random urine sample
Measure albumin and creatinine and look at the ratio between them
Why is nephropathy important?
Diabetic kidney disease = biggest reason for dialysis in the UK
Associated with increased risk of CVD events
How do microvascular complications in diabetics influence macrovascular complications?
Microvascular complications from diabetes e.g. CKD = increases the risk of macrovascular complications e.g. ischemic heart disease, peripheral vascular disease, cerebrovascular disease etc.
How do the glomeruli change with diabetic nephropathy?
Mesangial expansion
Basement membrane thickening
Glomerulosclerosis
How common is diabetic nephropathy in T1DM and T2DM?
T1DM: 20-40% after 30-40 years
T2DM: Probably equivalent but many other factors modifying the risk: age at development of disease, ethnic differences, age at presentation
How is diabetic nephropathy diagnosed?
Progressive proteinuria - urine ACR
Increased BP
Deranged renal function (eGFR)
Advanced: peripheral oedema
What are the boundaries for microalbuminuria?
> 2.5 mg/mmol (men)
3.5 mg/mmol (women)
Proteinuria = ACR >30mg/mmol
What is the mechanism for the development of diabetic nephropathy?
Hypertension and hyperglycaemia from diabetes lead to Increased glomerular hypertension Leads to proteinuria Glomerular and interstitial fibrosis eGFR decline Eventually renal failure
Ask Anouk
What are the strategies for intervention of diabetic nephropathy?
- Decreasing HbA1c reduces risk of microvasclar complications
- Managing BP (anti-hypertensive treatment) allows for slower decrease in eGFR and reduces albuminuria
- Inhibit renal-angiotensin-aldosterone system (RAS) - reduces creatinine levels
- SGLT-2 inhibition reduces degree of microalbuminuria and slower decrease in eGFR
Why do RAS blockades work?
Angiotensin 2 involved in inflammatory factors that affect the glomerulus
So RAS blockades reduce incidence of nephropathy
Give a summary for nephropathy treatment:
Aim for tighter glycaemic control Reduce BP as much as tolerated RAS blockading agent Stop smoking Start SGLT-2 inhibitors
What is diabetic neuropathy?
Small blood vessels called vasa nervorum supply nerves
Neuropathy = results from blockage of these vessels
Why are feet affected first in diabetic neuropathy?
Longest nerves supply feet - most peripheral
Manifests as loss of sensation
More common in tall people
Danger is that patients will not sense injury to the foot
Can lead to lower limb amputation
How is this (peripheral neuropathy) screened for?
All diabetics have foot checks annually
Assessed for using a 10g monofilament (tests for loss of sensation)
What are the clinical features of peripheral neuropathy?
Loss of sensation Loss of vibration sense Loss of temperature sensation Loss of propioception Loss of ankle jerks
How can peripheral neuropathy be managed?
- Good glycaemic control
- Regular inspection of feet - at least once a week
- Good footwear - without can lead to calluses and ulcerations
- Avoid barefoot walking
- For severe neuropathy - refer to podiatry and chiropody
What happens if a patient has an ulcer in their foot?
Medical emergency MDT diabetes foot clinic Offload pressure - give them good footwear Revascularisation to improve blood flow Antibiotics if infected Amputation if all else fails
What are some other neuropathies?
Mononeuropathy - CN palsy
Mononeurotis multiplex - a random combination of nerve lesions
Radiculopathy - pain over spinal nerves, usually affects dermatome on abdo or chest wall
Autonomic neuropathy - loss of sympathetic and parasympathetic nerves to GI tract, bladder, CVS
What is mononeuropathy?
Usually sudden motor loss: wrist drop, foot drop, CN palsy; double vision due to 3rd nerve palsy
What is autonomic neuropathy?
Loss of sympathetic and parasympathetic nerves to GI tract, bladder, CVS
GI tract: difficulty swallowing, delayed gastric emptying leads to nausea and vomiting, constipation, diarrhoea, bladder dysfunction
CV (cardiovascular): postural hypotension - can be disabling, lead to collapsing on standing; cardiac autonomic supply affected - case reports of sudden cardiac deaths
